Randomized Trial of Lenalidomide, Bortezomib, Dexamethasone vs High-Dose Treatment With SCT in MM Patients up to Age 65 (DFCI 10-106)

• ClinicalTrials.gov Identifier: NCT01208662
• Recruitment Status: Active, not recruiting
• First Posted: September 24, 2010
• Results First Posted: December 18, 2023
• Last Update Posted: December 18, 2023
• Sponsor: Paul Richardson, MD
• Collaborators: Celgene Corporation; Millennium Pharmaceuticals, Inc.; Massachusetts General Hospital; Cape Cod Hospital; Beth Israel Deaconess Medical Center; Emory University; University of Michigan; Fox Chase Cancer Center; Memorial Sloan Kettering Cancer Center; Fred Hutchinson Cancer Center; Barbara Ann Karmanos Cancer Institute; Duke University; University of California, San Francisco; University of Chicago; M.D. Anderson Cancer Center; UNC Lineberger Comprehensive Cancer Center; Roswell Park Cancer Institute; Stanford University; University of Mississippi Medical Center; Icahn School of Medicine at Mount Sinai; Wake Forest University Health Sciences; University of Arizona; OHSU Knight Cancer Institute; Eastern Maine Medical Center; University of California, San Diego; University of Alabama at Birmingham; University of Pittsburgh Medical Center; Ochsner Health System; University of Texas Southwestern Medical Center; State University of New York - Downstate Medical Center; Newton-Wellesley Hospital; Baylor College of Medicine; City of Hope Medical Center; University of Florida; Northwell Health; H. Lee Moffitt Cancer Center and Research Institute; Vanderbilt University Medical Center; Ohio State University; Huntsman Cancer Institute; Columbia University
• Information provided by (Responsible Party): Paul Richardson, MD, Dana-Farber Cancer Institute

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma
• Interventions: Drug: Lenalidomide; Drug: Bortezomib; Drug: Dexamethasone; Procedure: Autologous Stem Cell Transplant
• Enrollment: 729

Participant Flow

Recruitment Details	Participants were enrolled at 56 clinical sites in the U.S. from Oct 1, 2010 to January 30, 2018.
Pre-assignment Details

Arm/Group Title	RVD Alone	RVD Plus ASCT	RVD Cycle 1 Only
Arm/Group Description	All participants received one cycle of lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	Some participants started cycle 1 lenalidomide (R), bortezomib (V) and dexamethasone (D) therapy but were not randomized. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1) on days 1, 2, 4, 5, 8, 9, 11, and 12
Period Title: Induction and Consolidation
Started	357	365	7
Randomized [1]	357	365	0
Underwent Stem Cell Mobilization	324	330	0
Completed	291	289	0
Not Completed	66	76	7
Reason Not Completed
Disease Progression	23	13	0
Adverse Event	16	18	2
MD or Participant Decision	16	34	4
Death	1	3	1
Discontinued for other reasons	10	8	0
[1] Participants were randomized after 1 cycle of therapy only if cycle 1 therapy was completed and/or participant did not withdraw.
Period Title: Maintenance
Started	291	289	0
Minimal Residual Disease (MRD) Evaluable at Maintenance Start [1]	108	90	0
Completed [2]	0	0	0
Not Completed	291	289	0
Reason Not Completed
Disease Progression	156	102	0
Adverse Event	12	28	0
MD or Participant Decision	24	36	0
Death	0	3	0
Discontinued for other reasons	21	31	0
Still on Treatment	78	89	0
[1] MRD evaluable subset represents participants with clonal sequence identified at baseline plus MRD assessment at start of maintenance.; [2] Given maintenance treatment duration is not fixed, all participants are considered as 'Not Completed'.

Baseline Characteristics

Arm/Group Title		RVD Alone	RVD Plus ASCT	RVD Cycle 1 Only	Total
Arm/Group Description		All participants received one cycle of lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	Some participants started cycle 1 lenalidomide (R), bortezomib (V) and dexamethasone (D) therapy but were not randomized. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	Total of all reporting groups
Overall Number of Baseline Participants		357	365	7	729
Baseline Analysis Population Description		All enrolled participants.
Age, Continuous; Median (Inter-Quartile Range); Unit of measure: Years
	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		57; (25 to 66)	55; (30 to 65)	59; (55 to 65)	56; (50 to 61)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	357 participants	365 participants	7 participants	729 participants
	Female	155 43.4%	150 41.1%	3 42.9%	308 42.2%
	Male	202 56.6%	215 58.9%	4 57.1%	421 57.8%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	357 participants	365 participants	7 participants	729 participants
	Hispanic or Latino	19 5.3%	23 6.3%	0 0.0%	42 5.8%
	Not Hispanic or Latino	336 94.1%	332 91.0%	7 100.0%	675 92.6%
	Unknown or Not Reported	2 0.6%	10 2.7%	0 0.0%	12 1.6%
Race/Ethnicity, Customized; Measure Type: Count of Participants; Unit of measure: Participants
White	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		268 75.1%	272 74.5%	5 71.4%	545 74.8%
Black	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		66 18.5%	66 18.1%	2 28.6%	134 18.4%
Asian	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		8 2.2%	12 3.3%	0 0.0%	20 2.7%
Other	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		9 2.5%	9 2.5%	0 0.0%	18 2.5%
Unknown	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		6 1.7%	6 1.6%	0 0.0%	12 1.6%
Region of Enrollment; Measure Type: Number; Unit of measure: Participants
United States	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		357	365	7	729
ISS Multiple Myeloma Stage [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
I	Number Analyzed	357 participants	365 participants	0 participants	722 participants
		178 49.9%	184 50.4%		362 50.1%
II	Number Analyzed	357 participants	365 participants	0 participants	722 participants
		130 36.4%	134 36.7%		264 36.6%
III	Number Analyzed	357 participants	365 participants	0 participants	722 participants
		49 13.7%	47 12.9%		96 13.3%
		[1] Measure Description: The International Staging System (ISS) consists of three stages: stage I, serum beta 2-microglobulin level lower than 3.5 mg per liter and serum albumin level 3.5 g per deciliter or higher; stage II, neither stage I nor III; and stage III, serum beta 2-microglobulin level 5.5 mg per liter or higher. Higher stages indicate more severe disease.; [2] Measure Analysis Population Description: ISS Multiple Myeloma staging data collected at randomization and therefore data was not collected for the seven participants who were not randomized.
Cytogenetic Risk Category [1] [2]; Measure Type: Count of Participants; Unit of measure: Participants
High risk	Number Analyzed	357 participants	365 participants	0 participants	722 participants
		66 18.5%	66 18.1%		132 18.3%
Standard risk	Number Analyzed	357 participants	365 participants	0 participants	722 participants
		268 75.1%	274 75.1%		542 75.1%
		[1] Measure Description: Cytogenetic risk was based on FISH or karyotype analysis; patients who had a high-risk cytogenetic profile had at least one high-risk abnormality (t[4;14], t[14;16], or del17p). Patients with standard risk had no high-risk cytogenetic abnormalities.; [2] Measure Analysis Population Description: Cytogenetic risk category data collected at randomization and therefore data was not collected for the seven participants who were not randomized.
BMI [1]; Measure Type: Count of Participants; Unit of measure: Participants
<25	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		80 22.4%	81 22.2%	1 14.3%	162 22.2%
25 to <30	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		141 39.5%	127 34.8%	2 28.6%	270 37.0%
>/= 30	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		136 38.1%	157 43.0%	4 57.1%	297 40.7%
		[1] Measure Description: The body-mass index (BMI) is the weight in kilograms divided by the square of the height in meters.
ECOG Performance Status [1]; Measure Type: Count of Participants; Unit of measure: Participants
0	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		153 42.9%	164 44.9%	4 57.1%	321 44.0%
1	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		177 49.6%	161 44.1%	3 42.9%	341 46.8%
2	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		27 7.6%	39 10.7%	0 0.0%	66 9.1%
Unknown	Number Analyzed	357 participants	365 participants	7 participants	729 participants
		0 0.0%	1 0.3%	0 0.0%	1 0.1%
		[1] Measure Description: Eastern Cooperative Oncology Group (ECOG) Performance Status: (PS0) Fully active, able to carry on all pre-disease performance without restriction (PS1) Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature (PS2) Ambulatory and capable of all self-care but unable to carry out any work activities; Up and about >50% of waking hours.

Outcome Measures

1. Primary Outcome

Title	Median Progression-Free Survival (PFS)
Description	PFS was estimated using the Kaplan-Meier (KM) method and defined as time from randomization to the earlier of disease progression (PD) as determined by central review or death from any cause (events). Patients who started non-protocol therapy (NPT) were censored at the date of NPT initiation if available or date treatment ended if date of NPT was missing. Deaths occurring beyond 1 year from the date last known progression-free are not counted as events and censored at date of last disease evaluation. Patients who had not started NPT, progressed, or died were censored at the date of last disease evaluation. PD was based upon the International Myeloma Working Group (IMWG) uniform response criteria. [Kumar S, et al Lancet Oncol 2016;17(8):e328-e346].
Time Frame	On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median (maximum) PFS follow-up was 70 and 129 months.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Median (95% Confidence Interval); Unit of Measure: months
	46.2; (38.1 to 53.7)	67.5 [1]; (58.6 to NA)

[1]

95% CI upper bound not estimable because data not mature enough. Specifically, with the follow-up observed as of data extraction, there were not enough events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Observed Stratified Log Rank Test (1-sided p-value)
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.53
	Confidence Interval	(2-Sided) 95%; 1.23 to 1.91
	Estimation Comments	[Not Specified]

2. Secondary Outcome

Title	Partial Response (PR) Rate
Description	The PR rate is the percentage of participants achieving PR or better on treatment and was evaluated based on the IMWG criteria. PR was defined as > 50% reduction of serum M-protein and reduction in 24-h urinary M-protein by > 90% or to < 200mg per 24 hours. If the serum and urine M-protein are unmeasurable, a > 50% decrease in the difference between involved and uninvolved free light chain levels is required in place of the M-protein criteria. If serum and urine M-protein are unmeasurable, and serum free light assay is also unmeasurable, >50% reduction in plasma cells is required in place of M-protein, provided baseline bone marrow plasma cell percentage was > 30%. In addition to the above listed criteria, if present at baseline, a > 50% reduction in the size of soft tissue plasmacytomas was also required. Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes.
Time Frame	Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 133.5 months in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Number (99.29% Confidence Interval); Unit of Measure: percentage of participants
	95; (91.0 to 97.5)	97.5; (94.5 to 99.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.55
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

3. Secondary Outcome

Title	Very Good Partial Response (VGPR) Rate
Description	The VGPR rate is the percentage of participants achieving VGPR or better on treatment and was evaluated based on IMWG criteria. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or 90% or greater reduction in serum M-protein plus urine M-protein level <100mg per 24 hours.
Time Frame	Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 134 months in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	79.6; (73.3 to 85.0)	82.7; (76.8 to 87.7)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.99
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

4. Secondary Outcome

Title	Complete Response (CR) Rate
Description	The CR rate is the percentage of participants achieving CR or better on treatment and was evaluated based on IMWG criteria. CR was defined as the negative immunofixation on the serum and urine and disappearance of any soft tissue plasmacytomas and <5% plasma cells in bone marrow. Confirmation with repeat bone marrow biopsy was not needed.
Time Frame	Disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 134 months in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized patients.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of patients
	42.0; (35.0 to 49.3)	46.8; (39.8 to 54.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.99
	Comments	[Not Specified]
	Method	Fisher Exact
	Comments	[Not Specified]

5. Secondary Outcome

Title	Median Duration of Response: Partial Response (DOR PR)
Description	DOR PR was estimated using the KM method and defined as the time from documented best response as CR to documented disease progression per IMWG criteria. Patients who have not progressed or died were censored at the date last known progression-free.
Time Frame	On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median (maximum) DOR PR follow-up was 62.9 and 122.9 months.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants who achieved PR.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	339	356
Median (95% Confidence Interval); Unit of Measure: months
	38.9; (30.8 to 45.6)	56.4; (47.4 to 75.8)

6. Secondary Outcome

Title	5-Year Time to Progression (TTP)
Description	TTP was estimated using the KM method and defined as time from randomization to time of documented IMWG disease progression or censoring time (time of last disease evaluation for those alive, time to death among those who died). Patients initiating non-protocol therapy prior to progression or death were censored at the date of non-protocol therapy in the TTP analysis. The 5-year TTP endpoint is a probability.
Time Frame	On treatment, disease was assessed every cycle up to maintenance and every 3 cycles on maintenance. In long-term follow-up, disease was assessed every 2 months until PD or death. Median TTP follow-up was 70 months. The probability estimate is at 5 years.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percent probability
	41.6; (35.8 to 47.3)	58.4; (52.2 to 64.2)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	<0.001
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.66
	Confidence Interval	(2-Sided) 99.29%; 1.21 to 2.27
	Estimation Comments	[Not Specified]

7. Secondary Outcome

Title	5-Year Overall Survival (OS)
Description	OS was estimated using the KM method and defined as time from randomization to death due to any cause. Patients alive were censored at date last known alive. The 5-year OS endpoint is a probability.
Time Frame	In long-term follow-up, survival follow-up every 2 months until death. Median (maximum) OS follow-up was 76 and 129 months.The probability estimate is at 5 years.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percent probability
	79.2; (74.3 to 83.3)	80.7; (76.1 to 84.6)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	>0.99
	Comments	[Not Specified]
	Method	Log Rank
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 95%; 0.73 to 1.65
	Estimation Comments	[Not Specified]

8. Secondary Outcome

Title	Grade 3 or Higher Treatment-Related Non-Hematologic Adverse Event (AE) Rate
Description	Safety was evaluated throughout trial treatment, including ASCT, and through 30 days after receipt of the last dose of a trial drug. Treatment attribution and grade were based on the NCI CTCAE v4. The Grade 3 or Higher Treatment-Related Non-Hematologic AE Rate is percentage of participants who experienced any grade 3-5 treatment-related (possible, probable or definite attribution) non-hematologic adverse event based on CTCAEv4 as reported on case report forms. The difference in the rate of all grade 3 or higher toxicities was compared between the two groups using Fisher's exact test.
Time Frame	AEs was assessed every cycle on treatment. Median treatment duration (months) from randomization 28.2 (RVD Alone) and 36.1 (RVD plus ASCT). Maximum treatment duration was 133.5 months in this study cohort.

Outcome Measure Data

Analysis Population Description

The analysis population comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	78.2; (73.5 to 82.3)	94.2; (91.3 to 96.4)

9. Secondary Outcome

Title	5-year Cumulative Incidence of Second Primary Malignancy (SPM)
Description	Second primary malignancy (SPM) is defined as the development of another new, unrelated cancer, regardless of treatment for previous malignancy attribution. The cumulative incidence of SPMs was estimated with death as a competing risk. SPMs were collected using an SAE form or MEDWATCH 3500A form, with intensity determined by using the NCI CTCAE version 4 as a guideline.
Time Frame	5 years

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Measure Type: Number; Unit of Measure: percentage of patients
	4.9	6.5

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	Exact (Clopper-Pearson) confidence limits of 98.2857% represents Bonferroni adjustment for 7 tests (1-0.05/7) per statistical analysis plan for key secondary outcomes.
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.99
	Comments	[Not Specified]
	Method	Log Rank
	Comments	Stratified
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.10
	Confidence Interval	(2-Sided) 99.29%; 0.73 to 1.65
	Estimation Comments	[Not Specified]

10. Secondary Outcome

Title	Median Treatment Duration
Description	Treatment duration estimated using the KM method is defined as the time from registration (C1) to the time off treatment (event) or censored at date of last treatment.
Time Frame	Up to 134 months

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Median (95% Confidence Interval); Unit of Measure: months
	28.2; (21.2 to 37.1)	36.8; (29.0 to 42.2)

11. Secondary Outcome

Title	Median Maintenance Treatment Duration
Description	Maintenance treatment duration estimated using the KM method is defined as the time from start of maintenance to the time off maintenance (event) or censored at date of last maintenance treatment.
Time Frame	Up to 128 months

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all patients that started maintenance treatment.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	291	289
Median (95% Confidence Interval); Unit of Measure: months
	36.4; (25.7 to 40.8)	41.5; (34.0 to 47.1)

12. Secondary Outcome

Title	Subsequent Therapy Rate
Description	Subsequent therapy rate was the percentage of participants who discontinued treatment and initiated subsequent non-protocol therapy.
Time Frame	Up to 129 months

Outcome Measure Data

Analysis Population Description

All participants off treatment per protocol.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	279	276
Measure Type: Count of Participants; Unit of Measure: Participants
	222 79.6%	192 69.6%

13. Secondary Outcome

Title	Change From Baseline on the Functional Assessment of Cancer Therapy/Gynecologic Oncology Group-Neurotoxicity (FACT/GOG-NTX)
Description	The FACT/GOG-NTX assessment consists of 11 questions that are all used to construct 1 subscale to summarize symptoms of peripheral neuropathy, including sensory, motor, and auditory problems and cold sensitivity. (https://www.facit.org/measures/FACT-GOG-NTX) Each question has 4 possible responses from 0 (Not at all) to 4 (Very Much) which are reverse-scored and summed. This sum is then scaled by the number of questions answered by multiplying by 11 and then dividing by the number of questions that are non-blank, in order to keep all final scores proportional to one another even if some questions are left blank. The aggregate score ranges from 0 to 44, with higher scores indicating less neurotoxicity and lower scores indicating more neurotoxicity. Change from baseline is the difference
Time Frame	Cycle 1 (Baseline), Cycle 2, Pre-Mobilization, Cycle 5 Arm A / Post Auto-HSCT Arm B, Cycle 8 Arm A /Cycle 5 Arm B, Maintenance Day 1, 2 years from baseline, 3 years from baseline

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants who completed the assessment both at baseline and at the respective timepoint on treatment.

Arm/Group Title		RVD Alone	RVD Plus ASCT
Arm/Group Description:		All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed		357	365
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 2	Number Analyzed	255 participants	271 participants
		-1.8 (4.8)	-1.3 (5.0)
Pre-Mobilization	Number Analyzed	209 participants	206 participants
		-3.9 (6.9)	-3.5 (7.4)
Cycle 5 Arm A / Post Auto-HSCT Arm B	Number Analyzed	235 participants	151 participants
		-4.4 (6.5)	-4.4 (7.5)
Cycle 8 Arm A /Cycle 5 Arm B	Number Analyzed	212 participants	203 participants
		-4.7 (6.7)	-2.5 (6.5)
Maintenance Day 1	Number Analyzed	164 participants	166 participants
		-3.7 (6.9)	-2.3 (6.4)
2 years from baseline	Number Analyzed	99 participants	118 participants
		-4.9 (6.8)	-2.6 (6.1)
3 years from baseline	Number Analyzed	85 participants	93 participants
		-4.6 (7.4)	-3.2 (7.2)

14. Secondary Outcome

Title	Change From Baseline on the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire Core 30 (EORTC QLQ-C30): Global Health Status/Quality of Life (QoL) Sub-scale
Description	The EORTC QLQ-C30 assessment consists of 30 questions that are used to construct 15 distinct sub-scales (five function scales, nine symptom scales, and a global health status/QoL scale). The global health status/QoL scale is comprised of two questions each with a range of 6 (1=Very Poor to 7=Excellent). Scores on all sub-scales range from 0 to 100 after linear transformation of the raw scores, with higher scores representing better global health status and quality of life.
Time Frame	Cycle 1 (Baseline), Cycle 2, Pre-Mobilization, Cycle 5 Arm A / Post Auto-HSCT Arm B, Cycle 8 Arm A /Cycle 5 Arm B, Maintenance Day 1, 2 years from baseline, 3 years from baseline

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants who completed the assessment both at baseline and at the respective timepoint on treatment.

Arm/Group Title		RVD Alone	RVD Plus ASCT
Arm/Group Description:		All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed		357	365
Mean (Standard Deviation); Unit of Measure: units on a scale
Cycle 2	Number Analyzed	257 participants	282 participants
		0.1 (20.8)	4.3 (21.8)
Pre-Mobilization	Number Analyzed	230 participants	234 participants
		0.4 (21.7)	4.4 (23.8)
Cycle 5 Arm A / Post Auto-HSCT Arm B	Number Analyzed	239 participants	170 participants
		3.0 (24.8)	-11.1 (28.9)
Cycle 8 Arm A /Cycle 5 Arm B	Number Analyzed	224 participants	206 participants
		1.2 (23.5)	8.3 (25.2)
Maintenance Day 1	Number Analyzed	186 participants	190 participants
		5.3 (23.0)	9.9 (23.6)
2 years from baseline	Number Analyzed	107 participants	127 participants
		5.1 (22.4)	11.1 (26.0)
3 years from baseline	Number Analyzed	89 participants	98 participants
		3.5 (23.6)	12.7 (27.4)

15. Secondary Outcome

Title	Quality-Adjusted Life Years (QALYs)
Description	QALYs were estimated with a model beginning at initiation of first-line therapy by arm. A lifetime horizon, as well as subsequent lines of therapy, was examined using open-source Amua 0.3.0 software. Base case analysis was performed using 10,000 first-order Monte Carlo simulations. Conditional probabilities were extracted from Kaplan-Meier curves from pivotal clinical trials using WebPlotDigitizer. Costs were estimated from RED BOOK and DFCI charge reporting in US Dollars ($) after inflation adjustment to 2022 and 3% discounting, and QALYs effects were measured using EQ-5D data from Hatswell et al.
Time Frame	Maximum observation of survival for this study cohort was 129.4 months.

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Mean (Standard Deviation); Unit of Measure: years gained
	5.67 (3.52)	6.10 (3.59)

16. Post-Hoc Outcome

Title	Next Generation Sequencing (NGS) Minimal Residual Disease Negative (MRD-) Rate at Maintenance Start
Description	Bone marrow aspirate samples were obtained from patients prior to the start of lenalidomide maintenance. NGS MRD- rate is the percentage of evaluable participants with MRD level of <1 x 10-5 (indicating detection of 1 malignant plasma cell in 100,000 bone marrow cells) using the validated, US Food and Drug Administration approved clonoSEQ® NGS platform (Adaptive Biotechnologies) with a minimum sensitivity of 1 x 10-5.
Time Frame	Maintenance treatment occurred after induction, up to 11.5 months.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of the participants with evaluable samples at baseline and start of maintenance.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	108	90
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: percentage of participants
	39.8; (30.5 to 49.7)	54.4; (43.6 to 65.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	RVD Alone, RVD Plus ASCT
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Odds Ratio (OR)
	Estimated Value	0.55
	Confidence Interval	(2-Sided) 95%; 0.30 to 1.01
	Estimation Comments	[Not Specified]

17. Post-Hoc Outcome

Title	Median Event Free Survival (EFS)
Description	EFS was estimated using the KM method and defined as the time from randomization to the earliest of IMWG disease progression, death, or initiation of non-protocol therapy (events); patients were censored date of last disease evaluation.
Time Frame	Assessed up to approximately 130 months.

Outcome Measure Data

Analysis Population Description

The analysis population is comprised of all randomized participants.

Arm/Group Title	RVD Alone	RVD Plus ASCT
Arm/Group Description:	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12
Overall Number of Participants Analyzed	357	365
Median (95% Confidence Interval); Unit of Measure: months
	32.0; (23.5 to 42.0)	47.3; (41.3 to 55.5)

Adverse Events

Time Frame	Assessed throughout the treatment period, from time of first dose and up to day 30 post-treatment. Maximum treatment duration was 133.5 months in this study cohort.
Adverse Event Reporting Description	Serious AEs were defined as events with treatment-attribution of possibly, probably or definitely and grade 3 or higher per CTCAEv4. This is not the same definition of SAE per protocol but parallels the publication. Other AEs were defined as events with treatment-attribution of possible, probable or definite and grades 1 or 2 per CTCAEv4. Maximum grade toxicity by type was then calculated. No further data is available to specify classification of other beyond the general term.
Arm/Group Title	RVD Alone	RVD Plus ASCT	RVD Cycle 1 Only
Arm/Group Description	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (D) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD Alone participants received five additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, off-study salvage transplantation was recommended but not mandated for RVD Alone participants at relapse. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	All participants received one cycle of Lenalidomide (R), bortezomib (V) and dexamethasone (d) and then were randomized. All participants then received two additional RVD cycles, followed by stem-cell collection. RVD plus autologous stem cell transplant (ASCT) participants received high-dose melphalan (200 mg/m2, adjusted for ideal body weight) ASCT and, upon recovery (~day 60), two additional RVD cycles. Maintenance in both arms comprised daily lenalidomide 10 mg, escalated to 15 mg if tolerated, until disease progression, unacceptable toxicity, or withdrawal from treatment or study. After finishing protocol-specified treatment, RVD plus ASCT participants could undergo a second transplant. RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1-3) or 10 mg (cycles 4-8) on days 1, 2, 4, 5, 8, 9, 11, and 12	RVD cycle duration=21 days R: 25 mg oral on days 1-14 V: 1.3 mg per square meter of body surface area IV or subcutaneous on days 1, 4, 8, and 11 D: 20 mg oral (cycles 1) on days 1, 2, 4, 5, 8, 9, 11, and 12
All-Cause Mortality
	RVD Alone	RVD Plus ASCT	RVD Cycle 1 Only
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	89/357 (24.93%)	88/365 (24.11%)	1/7 (14.29%)
Serious Adverse Events
	RVD Alone	RVD Plus ASCT	RVD Cycle 1 Only
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	279/357 (78.15%)	344/365 (94.25%)	4/7 (57.14%)
Blood and lymphatic system disorders
Anemia † 1	65/357 (18.21%)	108/365 (29.59%)	1/7 (14.29%)
Febrile neutropenia † 1	15/357 (4.20%)	33/365 (9.04%)	0/7 (0.00%)
Leukocytosis † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Leukopenia † 1	70/357 (19.61%)	145/365 (39.73%)	1/7 (14.29%)
Lymph node pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lymphopenia † 1	32/357 (8.96%)	37/365 (10.14%)	0/7 (0.00%)
Neutropenia † 1	152/357 (42.58%)	315/365 (86.30%)	1/7 (14.29%)
Pancytopenia † 1	0/357 (0.00%)	9/365 (2.47%)	0/7 (0.00%)
Thrombocytopenia † 1	71/357 (19.89%)	302/365 (82.74%)	1/7 (14.29%)
Cardiac disorders
Acute coronary syndrome † 1	0/357 (0.00%)	0/365 (0.00%)	1/7 (14.29%)
Acute heart failure † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Acute pericarditis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Atrial fibrillation † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
atrial flutter † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bradycardia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Conduction disorder † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Congestive heart failure † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Heart block † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Heart failure † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Myocardial infarction † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Paroxysmal atrial fibrillation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Endocrine disorders
Hypothyroidism † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eye disorders
Retinal vascular disorder † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastrointestinal disorders
Abdominal discomfort † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Abdominal pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Acute pancreatitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Colitis † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Constipation † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Diarrhea † 1	15/357 (4.20%)	18/365 (4.93%)	0/7 (0.00%)
Dysphasia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Esophagitis † 1	0/357 (0.00%)	10/365 (2.74%)	0/7 (0.00%)
Gastric ulcer † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastritis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastroesophageal reflux disease † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gastrointestinal bleed † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Gastrointestinal hemorrhage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastrointestinal obstruction † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Lower gastrointestinal hemorrhage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mucositis † 1	19/357 (5.32%)	0/365 (0.00%)	0/7 (0.00%)
Nausea † 1	2/357 (0.56%)	24/365 (6.58%)	0/7 (0.00%)
Odynophagia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Oedema uvula † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pancreatitis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Rectal hemorrhage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Stomach pain † 1	13/357 (3.64%)	0/365 (0.00%)	0/7 (0.00%)
Typhlitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vomiting † 1	2/357 (0.56%)	11/365 (3.01%)	0/7 (0.00%)
General disorders
Chest pain † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Edema † 1	5/357 (1.40%)	5/365 (1.37%)	0/7 (0.00%)
Edema NOS † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Fatigue † 1	10/357 (2.80%)	22/365 (6.03%)	0/7 (0.00%)
Fever † 1	7/357 (1.96%)	19/365 (5.21%)	0/7 (0.00%)
Malaise † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mucositis † 1	6/357 (1.68%)	0/365 (0.00%)	0/7 (0.00%)
Pain † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Pain NOS † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Physical deconditioning † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sternal pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sudden death † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Weakness † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Hepatobiliary disorders
Cholecystitis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Gallbladder inflammation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hyperbilirubinemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Immune system disorders
Graft versus host disease † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Infections and infestations
Abcess † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Abdominal abscess † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Acute sinusitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Bacteremia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Bacterial infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Breast cellulitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Catheter infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cellulitis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Clostridium difficile infection † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Empyema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Endocarditis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Enterocolitis infectious † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Escherichia coli infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastroenteritis † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Herpes zoster † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Infection NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Influenza † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Kidney infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Leptotrichia buccalis infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lip infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lobar pneumonia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Necrotizing fasciitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nose infection NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nosocomial pneumonia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Papulopustular rash † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pneumonia † 1	18/357 (5.04%)	33/365 (9.04%)	0/7 (0.00%)
Respiratory syncytial virus infection † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Sepsis † 1	3/357 (0.84%)	8/365 (2.19%)	0/7 (0.00%)
Shingles † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Sinusitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Soft tissue infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Stomach virus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Streptococcal bacteremia † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Streptococcal infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Thrush † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Upper respiratory infection † 1	1/357 (0.28%)	9/365 (2.47%)	0/7 (0.00%)
Urinary tract infection † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Viral pneumonia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Viral syndrome † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Injury, poisoning and procedural complications
Fall † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Subdural hematoma † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Investigations
Absolute lymphocyte count decreased † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Aspartate aminotransferase increased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blood bilirubin increased † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Blood creatinine increased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Creatine kinase high † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Creatinine increased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Elevated liver enzymes † 1	8/357 (2.24%)	8/365 (2.19%)	1/7 (14.29%)
QT interval prolonged † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Weight gain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Weight loss † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
White blood cell count increased † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Metabolism and nutrition disorders
Anorexia † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Decreased appetite † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dehydration † 1	6/357 (1.68%)	4/365 (1.10%)	0/7 (0.00%)
Hyperglycemia † 1	9/357 (2.52%)	15/365 (4.11%)	0/7 (0.00%)
Hyperuricemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hypocalcemia † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Hypokalemia † 1	12/357 (3.36%)	7/365 (1.92%)	0/7 (0.00%)
Hyponatremia † 1	6/357 (1.68%)	7/365 (1.92%)	0/7 (0.00%)
Hypophosphatemia † 1	34/357 (9.52%)	30/365 (8.22%)	0/7 (0.00%)
Metabolic acidosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tumor lysis syndrome † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Musculoskeletal and connective tissue disorders
Ache † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Back pain † 1	4/357 (1.12%)	0/365 (0.00%)	0/7 (0.00%)
Bone pain † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Generalized muscle weakness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Muscle cramps † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Muscle spasm † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Myalgia † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Osteonecrosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Osteonecrosis of jaw † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Pain in elbow † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain in extremity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain in hand † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain in hip † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Pain in Neck † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pain joint † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rib pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Weakness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Acute lymphoblastic leukemia † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Acute lymphocytic leukemia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Acute myeloid leukemia † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Adenocarcinoma of colon † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Basal cell carcinoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Breast cancer † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Breast ductal cancer invasive † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Ductal carcinoma in situ † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Leukemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lung adenocarcinoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Melanoma † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Melanoma in situ † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Myelodysplastic syndrome † 1	0/357 (0.00%)	5/365 (1.37%)	0/7 (0.00%)
Second primary malignancy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Squamous cell carcinoma † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Treatment related secondary malignancy † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Nervous system disorders
Brain stem stroke † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dizziness † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Encephalomalacia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Headache † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Memory impairment † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Neuropathy † 1	3/357 (0.84%)	7/365 (1.92%)	0/7 (0.00%)
Sensory peripheral neuropathy † 1	17/357 (4.76%)	19/365 (5.21%)	0/7 (0.00%)
Somnolence † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Stroke † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Syncope † 1	8/357 (2.24%)	7/365 (1.92%)	0/7 (0.00%)
Psychiatric disorders
Anxiety † 1	0/357 (0.00%)	4/365 (1.10%)	0/7 (0.00%)
Confusion † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Depression † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Insomnia † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Mental status changes † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Renal and urinary disorders
Incontinence † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory distress syndrome † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Chronic obstructive pulmonary disease † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dyspnea † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Epistaxis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hypoxia † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pneumonitis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Productive cough † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pulmonary mass † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Respiratory failure † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Throat pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin and subcutaneous tissue disorders
Alopecia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dry skin † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Erythema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Facial swelling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Photosensitivity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rash erythematous † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rash maculo-papular † 1	10/357 (2.80%)	13/365 (3.56%)	1/7 (14.29%)
Rash pruritic † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Stevens Johnson syndrome † 1	0/357 (0.00%)	0/365 (0.00%)	1/7 (14.29%)
Surgical and medical procedures
Cholecystostomy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vascular disorders
Deep vein thrombosis † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Hypertension † 1	5/357 (1.40%)	8/365 (2.19%)	0/7 (0.00%)
Hypotension † 1	4/357 (1.12%)	9/365 (2.47%)	0/7 (0.00%)
Hypotension orthostatic † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Pulmonary embolism † 1	5/357 (1.40%)	8/365 (2.19%)	0/7 (0.00%)
Thromboembolic event † 1	3/357 (0.84%)	6/365 (1.64%)	0/7 (0.00%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	0%
	RVD Alone	RVD Plus ASCT	RVD Cycle 1 Only
	Affected / at Risk (%)	Affected / at Risk (%)	Affected / at Risk (%)
Total	343/357 (96.08%)	345/365 (94.52%)	7/7 (100.00%)
Blood and lymphatic system disorders
Anemia † 1	51/357 (14.29%)	65/365 (17.81%)	0/7 (0.00%)
Cytopenia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eosinophilia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Febrile neutropenia † 1	4/357 (1.12%)	8/365 (2.19%)	0/7 (0.00%)
Leukocytosis † 1	1/357 (0.28%)	4/365 (1.10%)	0/7 (0.00%)
Leukopenia † 1	50/357 (14.01%)	67/365 (18.36%)	1/7 (14.29%)
Lymph node pain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Lymph nodes enlarged † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lymphadenitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lymphadenopathy † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Lymphopenia † 1	32/357 (8.96%)	25/365 (6.85%)	0/7 (0.00%)
Neutropenia † 1	62/357 (17.37%)	95/365 (26.03%)	1/7 (14.29%)
Pancytopenia † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Swollen glands † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Swollen lymph nodes † 1	0/357 (0.00%)	4/365 (1.10%)	0/7 (0.00%)
Thrombocytopenia † 1	40/357 (11.20%)	84/365 (23.01%)	2/7 (28.57%)
Thrombocytosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cardiac disorders
Acute pericarditis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Arrhythmia † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Asystole † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Atrial fibrillation † 1	5/357 (1.40%)	5/365 (1.37%)	0/7 (0.00%)
Atrial flutter † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Bradycardia † 1	29/357 (8.12%)	24/365 (6.58%)	0/7 (0.00%)
Cardiac arrest † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cardiac disorder † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Conduction disorder † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Congestive heart failure † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Coronary artery atherosclerosis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Coronary artery disease † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Heart enlarged † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mitral regurgitation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Mitral valve incompetence † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Mobitz type I † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Non ST segment elevation myocardial infarction † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Palpitations † 1	9/357 (2.52%)	11/365 (3.01%)	0/7 (0.00%)
Paroxysmal atrial fibrillation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pericardial effusion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pericarditis † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Sinus bradycardia † 1	19/357 (5.32%)	14/365 (3.84%)	0/7 (0.00%)
Sinus tachycardia † 1	1/357 (0.28%)	9/365 (2.47%)	0/7 (0.00%)
Tachycardia † 1	10/357 (2.80%)	28/365 (7.67%)	0/7 (0.00%)
Trigeminy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Congenital, familial and genetic disorders
Macroglossia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Ear and labyrinth disorders
Abnormal sensation in ear † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Ear ache † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Ear congestion † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Ear discomfort † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Ear disorder † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Ear feels clogged † 1	4/357 (1.12%)	3/365 (0.82%)	0/7 (0.00%)
Ear pain † 1	10/357 (2.80%)	16/365 (4.38%)	0/7 (0.00%)
Ear ringing † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Ear swelling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Ear wax † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Fluid in middle ear † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hearing impaired † 1	7/357 (1.96%)	13/365 (3.56%)	0/7 (0.00%)
Labyrinthine disorders † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Motion sickness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Perforation of tympanic membrane † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Ringing in ears † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Sensation of pressure in ear † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Tinnitus † 1	18/357 (5.04%)	14/365 (3.84%)	0/7 (0.00%)
Vertigo † 1	17/357 (4.76%)	10/365 (2.74%)	0/7 (0.00%)
Vestibular disorder † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Wax in ear † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Endocrine disorders
Adrenal insufficiency † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cushingoid † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Hashimoto's thyroiditis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hyperthyroidism † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hypothyroidism † 1	6/357 (1.68%)	5/365 (1.37%)	0/7 (0.00%)
Thyroid cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eye disorders
Abnormal vision † 1	5/357 (1.40%)	2/365 (0.55%)	0/7 (0.00%)
Anisocoria † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Astigmatism † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Blepharitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bloodshot eye † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blurred vision † 1	67/357 (18.77%)	41/365 (11.23%)	0/7 (0.00%)
Burning eyes † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Cataract † 1	7/357 (1.96%)	5/365 (1.37%)	0/7 (0.00%)
Chalazion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Conjunctival injection † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Conjunctivitis † 1	14/357 (3.92%)	14/365 (3.84%)	0/7 (0.00%)
Conjunctivitis, unspecified † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Diplopia † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Dry eyes † 1	30/357 (8.40%)	21/365 (5.75%)	0/7 (0.00%)
Edema of eyelid † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Erythema eyelid † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eye allergy † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eye disorder † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Eye edema † 1	4/357 (1.12%)	3/365 (0.82%)	0/7 (0.00%)
Eye floaters † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eye inflammation † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Eye irritation † 1	1/357 (0.28%)	5/365 (1.37%)	0/7 (0.00%)
Eye itching † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eye muscle weakness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eye pain † 1	10/357 (2.80%)	5/365 (1.37%)	0/7 (0.00%)
Eye redness † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Eyelid irritation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eyelid margin crusting † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eyelid twitching † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Eyelid twitching † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Eyes swollen † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Flashing lights † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Floaters † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Floaters in eye † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Glaucoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hyperopia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Irritation of eyes † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Itchy eyes † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Light sensitivity to eye † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Macular hole † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Mucus from eyes † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Periorbital edema † 1	5/357 (1.40%)	6/365 (1.64%)	0/7 (0.00%)
Photophobia † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Red eye † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Retinal atrophy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Retinal telangiectasia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Retro-orbital pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Scleral haemorrhage † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Sticky feeling in eyes † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Subconjunctival hemorrhage † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Subconjunctival hemorrhage † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Teary eyes † 1	5/357 (1.40%)	9/365 (2.47%)	1/7 (14.29%)
Tired eyes † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Uveitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vision abnormal † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Vision double † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vision loss † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Visual discomfort † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Visual disturbances † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Vitreous detachment † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gastrointestinal disorders
Abdominal crampy pains † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Abdominal discomfort † 1	8/357 (2.24%)	20/365 (5.48%)	0/7 (0.00%)
Abdominal distension † 1	26/357 (7.28%)	24/365 (6.58%)	0/7 (0.00%)
Abdominal pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Abdominal wall cyst † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Abnormal bowel sounds † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Acid reflux † 1	10/357 (2.80%)	11/365 (3.01%)	0/7 (0.00%)
Anal bleeding † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Anal fissure † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Anal hemorrhage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Anal lesion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Anal pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Belching † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Black stools † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Bleeding from tongue † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bleeding lips † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blister of lip † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blood in stool † 1	8/357 (2.24%)	11/365 (3.01%)	0/7 (0.00%)
Blood stool † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bowel cramps † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Bowel movement irregularity † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Buccal ulceration † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Burning sensation in abdomen † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Burning tongue † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Canker sore lip † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Canker sores oral † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Chronic gastritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Chronic heartburn † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Colitis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Colonic polyp † 1	4/357 (1.12%)	1/365 (0.27%)	0/7 (0.00%)
Constipation † 1	192/357 (53.78%)	196/365 (53.70%)	1/7 (14.29%)
Dental caries † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Dental cavity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dental disorder NOS † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Diarrhea † 1	192/357 (53.78%)	233/365 (63.84%)	0/7 (0.00%)
Distress gastrointestinal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dry heaves † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Dry lips † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Dry mouth † 1	34/357 (9.52%)	30/365 (8.22%)	0/7 (0.00%)
Duodenal ulcer † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dyspepsia † 1	34/357 (9.52%)	37/365 (10.14%)	0/7 (0.00%)
Dysphasia † 1	7/357 (1.96%)	11/365 (3.01%)	0/7 (0.00%)
Emesis † 1	2/357 (0.56%)	6/365 (1.64%)	0/7 (0.00%)
Emesis bloody † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Epigastric discomfort † 1	6/357 (1.68%)	6/365 (1.64%)	0/7 (0.00%)
Epigastric hernia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Esophageal pain † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Esophageal stenosis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Esophageal ulcer † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Esophagitis † 1	4/357 (1.12%)	24/365 (6.58%)	0/7 (0.00%)
Fecal incontinence † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Flatulence † 1	10/357 (2.80%)	23/365 (6.30%)	0/7 (0.00%)
Food poisoning † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Frequent bowel movements † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastric ulcer † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Gastritis † 1	4/357 (1.12%)	2/365 (0.55%)	0/7 (0.00%)
Gastritis erosive † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastroesophageal reflux disease † 1	3/357 (0.84%)	16/365 (4.38%)	0/7 (0.00%)
Gastrointestinal bleed † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Gastrointestinal discomfort † 1	10/357 (2.80%)	11/365 (3.01%)	0/7 (0.00%)
Gastrointestinal disorder † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Gastrointestinal hemorrhage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastrointestinal mucositis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gastrointestinal obstruction † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gastrointestinal pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastrointestinal symptom NOS † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Gastroparesis † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
GERD † 1	13/357 (3.64%)	17/365 (4.66%)	0/7 (0.00%)
Gingival hyperpigmentation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gingival pain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Gingivitis † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Gum bleeding † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Gum disorder † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Gum pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gum swelling † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Haemorrhoids † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Heartburn † 1	17/357 (4.76%)	16/365 (4.38%)	0/7 (0.00%)
Hemorrhage oral † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hemorrhoidal bleeding † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Hemorrhoids † 1	8/357 (2.24%)	5/365 (1.37%)	0/7 (0.00%)
Hernia inguinal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hiatal hernia † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Increased stool urgency † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Indigestion † 1	0/357 (0.00%)	4/365 (1.10%)	0/7 (0.00%)
Inguinal hernia † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Irritable bowel syndrome † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Irritation gum † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Irritation lips † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Left lower quadrant pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Left upper quadrant pain † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Lip sore † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lip ulceration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Loose motions † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Loose stools † 1	8/357 (2.24%)	19/365 (5.21%)	0/7 (0.00%)
Lower abdominal pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Melena † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Mouth cyst † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mouth ulceration † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mucositis † 1	22/357 (6.16%)	91/365 (24.93%)	0/7 (0.00%)
Nausea † 1	155/357 (43.42%)	218/365 (59.73%)	2/7 (28.57%)
Numbness lips † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Numbness of tongue † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Oral dysesthesia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Oral hemorrhage † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Oral lesion † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Oral mucosal erythema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
oral pain † 1	6/357 (1.68%)	6/365 (1.64%)	0/7 (0.00%)
Pain abdominal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain in tongue † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pain in tooth † 1	14/357 (3.92%)	15/365 (4.11%)	0/7 (0.00%)
Pain mouth † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pancreatitis † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Parotid gland inflammation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Perianal bleeding † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Periodontal disease † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Perioral numbness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Periumbilical pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Proctocolitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pyrosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rectal bleeding † 1	3/357 (0.84%)	7/365 (1.92%)	0/7 (0.00%)
Rectal blood loss † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rectal fissure † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rectal hemorrhage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rectal pain † 1	1/357 (0.28%)	6/365 (1.64%)	0/7 (0.00%)
Right upper quadrant pain † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Salivary hypersecretion † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sensitivity of teeth † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Small bowel obstruction † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Small intestinal obstruction † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Soft stools † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Sore mouth † 1	9/357 (2.52%)	9/365 (2.47%)	0/7 (0.00%)
Stomach ache † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Stomach pain † 1	69/357 (19.33%)	72/365 (19.73%)	0/7 (0.00%)
Stomachache † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Stomatitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Submaxillary gland swelling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Swallowing difficult † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Swelling of tongue † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tingling lips † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tongue blistering † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tongue disorder † 1	4/357 (1.12%)	0/365 (0.00%)	0/7 (0.00%)
Tongue edema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tongue swelling non-specific † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tongue ulceration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tooth ache † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Ulcer mouth † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Ulceration of intestine † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Umbilical hernia † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Upset stomach † 1	6/357 (1.68%)	7/365 (1.92%)	0/7 (0.00%)
Uvulitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vomiting † 1	64/357 (17.93%)	127/365 (34.79%)	2/7 (28.57%)
General disorders
Accidental death † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Acute pain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Adverse drug reaction † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Ankle edema † 1	7/357 (1.96%)	17/365 (4.66%)	0/7 (0.00%)
Application site bruise † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Asthenia † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Catheter site bleeding † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Catheter site bruise † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Catheter site erythema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Catheter site pain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Catheter site redness † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Chest discomfort † 1	3/357 (0.84%)	5/365 (1.37%)	0/7 (0.00%)
Chest fullness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Chest mass NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chest pain † 1	31/357 (8.68%)	58/365 (15.89%)	0/7 (0.00%)
Chest pain (non-cardiac) † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Chest tightness † 1	1/357 (0.28%)	7/365 (1.92%)	0/7 (0.00%)
Chills † 1	33/357 (9.24%)	48/365 (13.15%)	1/7 (14.29%)
Cold intolerance † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cold intolerance † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Cyst † 1	4/357 (1.12%)	6/365 (1.64%)	0/7 (0.00%)
Delayed healing of wound † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Difficulty in walking † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Drug intolerance † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Early satiety † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Edema † 1	157/357 (43.98%)	143/365 (39.18%)	0/7 (0.00%)
Edema arms † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Edema face † 1	7/357 (1.96%)	4/365 (1.10%)	0/7 (0.00%)
Edema knees † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Edema legs † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Excessive thirst † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Exercise tolerance decreased † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Extravasation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Facial pain † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Fatigue † 1	230/357 (64.43%)	235/365 (64.38%)	2/7 (28.57%)
Feeling jittery † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Feeling of warmth † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Feeling strange † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Fever † 1	96/357 (26.89%)	113/365 (30.96%)	2/7 (28.57%)
Fingers swollen feeling of † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Flu like symptoms † 1	41/357 (11.48%)	43/365 (11.78%)	0/7 (0.00%)
Flu-like illness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Flu-like symptoms † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Foggy feeling in head † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Foot edema † 1	4/357 (1.12%)	5/365 (1.37%)	0/7 (0.00%)
Gait disorder † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gait disturbance † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Generalized illness † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hand swelling † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Heat intolerance † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Heat sensitivity † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Hernia † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Hot feeling in hand † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Hypothermia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Increased thirst † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Inflammation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Inflammation localized † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Infusion site extravasation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Infusion site reaction † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Injection site reaction † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Injection site tenderness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Irritability † 1	13/357 (3.64%)	9/365 (2.47%)	0/7 (0.00%)
Jitteriness † 1	5/357 (1.40%)	0/365 (0.00%)	0/7 (0.00%)
Leg edema † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Malaise † 1	26/357 (7.28%)	20/365 (5.48%)	0/7 (0.00%)
Mass † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Neck edema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Neck swelling † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Nodule † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Nodule on extremity † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Non-cardiac chest pain † 1	1/357 (0.28%)	8/365 (2.19%)	0/7 (0.00%)
Oedema trunk † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain † 1	109/357 (30.53%)	105/365 (28.77%)	1/7 (14.29%)
Pain in face † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain localized † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Pain NOS † 1	8/357 (2.24%)	13/365 (3.56%)	0/7 (0.00%)
Polyp † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pyrexia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rigors † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Sacral edema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Slight temperature † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sternal pain † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Sternal pain † 1	2/357 (0.56%)	7/365 (1.92%)	0/7 (0.00%)
Suprapubic pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Swollen thumb † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Thirst † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Venipuncture site pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Weakness † 1	13/357 (3.64%)	21/365 (5.75%)	0/7 (0.00%)
Hepatobiliary disorders
Biliary dyskinesia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cholecystitis † 1	1/357 (0.28%)	6/365 (1.64%)	0/7 (0.00%)
Cholelithiasis † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Chronic cholecystitis † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Colic biliary † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gallbladder disease † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gallbladder pain † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Gallstones † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hepatic lesion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hepatic steatosis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hepatosplenomegaly † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hyperbilirubinemia † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Jaundice † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Immune system disorders
Allergic reaction † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Allergy † 1	6/357 (1.68%)	2/365 (0.55%)	0/7 (0.00%)
Amyloid disease † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Anaphylaxis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Graft versus host disease † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hypogammaglobulinaemia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Multiple allergies † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Seasonal allergy † 1	5/357 (1.40%)	3/365 (0.82%)	0/7 (0.00%)
Specific allergy (drug) † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Infections and infestations
Abcess † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Abdominal infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Abscess † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Abscess jaw † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Abscess limb † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Abscesses of skin † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Acute gastroenteritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Acute pharyngitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Acute vaginitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Anorectal infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Appendicitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Athlete's foot † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Atypical pneumonia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Axillary abscess † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Bacteremia † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Bacterial vaginosis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Bladder infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Boil † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bronchial infection † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Bronchiolitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bronchitis acute † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bronchitis viral † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Carbuncle † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Catheter infection † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Cellulitis † 1	8/357 (2.24%)	16/365 (4.38%)	0/7 (0.00%)
Cellulitis of arm † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cellulitis of thumb † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chest cold † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chest wall abscess † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chronic lower extremity cellulitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Clostridium difficile infection † 1	2/357 (0.56%)	10/365 (2.74%)	0/7 (0.00%)
Cold † 1	38/357 (10.64%)	41/365 (11.23%)	0/7 (0.00%)
Cold sore (herpetic) † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cold sores † 1	0/357 (0.00%)	5/365 (1.37%)	0/7 (0.00%)
Conjunctivitis bacterial † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Conjunctivitis infective † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Coronavirus infection † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Cystitis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Dental abscess † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Device related infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Diverticulitis † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Ear infection † 1	8/357 (2.24%)	5/365 (1.37%)	0/7 (0.00%)
Empyema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Enterocolitis infectious † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Enterovirus infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
External ear infection NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eye infection † 1	9/357 (2.52%)	4/365 (1.10%)	0/7 (0.00%)
Folliculitis † 1	5/357 (1.40%)	15/365 (4.11%)	0/7 (0.00%)
Fungal infection † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Fungal rash † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Gastroenteritis † 1	4/357 (1.12%)	9/365 (2.47%)	0/7 (0.00%)
Gastroenteritis norovirus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gastrointestinal infection † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Gastrointestinal viral infection † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Genital herpes † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
GI infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Groin abscess † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Gum infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Helicobacter pylori gastritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Helicobacter pylori infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hepatitis C † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Herpes labialis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Herpes simplex † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Herpes zoster † 1	8/357 (2.24%)	14/365 (3.84%)	0/7 (0.00%)
Herpes zoster multi-dermatomal † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hordeolum † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Human anaplasmosis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Human papilloma virus infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Ill-defined intestinal infections † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Infected cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Infected finger † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Infected thumb † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Infected toe † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Infection ingrowing toenail † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Infection localised † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Infection NOS † 1	4/357 (1.12%)	1/365 (0.27%)	0/7 (0.00%)
Infection staphylococcal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Influenza † 1	14/357 (3.92%)	17/365 (4.66%)	0/7 (0.00%)
Influenza B virus infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Kidney infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Labyrinthitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Laryngitis † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Left otitis externa † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lip infection † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Lyme disease † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Mucosal infection † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Mycosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nail fungal infection NOS † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Nail infection † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Nose infection NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nosocomial pneumonia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Oral candidiasis † 1	7/357 (1.96%)	12/365 (3.29%)	0/7 (0.00%)
Oral infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Orbital cellulitis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Otitis † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Otitis externa † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Otitis media † 1	0/357 (0.00%)	6/365 (1.64%)	0/7 (0.00%)
Otitis media † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Overgrowth bacterial † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Papulopustular rash † 1	6/357 (1.68%)	7/365 (1.92%)	0/7 (0.00%)
Paronychia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Parotiditis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Parotitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Periapical abscess without sinus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Periorbital cellulitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Perirectal abscess † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pharyngitis † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Pinkeye † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pneumonia † 1	38/357 (10.64%)	58/365 (15.89%)	0/7 (0.00%)
Pyelonephritis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Respiratory infection † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Respiratory syncytial virus infection † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Rhinitis † 1	9/357 (2.52%)	11/365 (3.01%)	0/7 (0.00%)
Rhinitis infective † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rhinovirus infection † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Rhinovirus infection NOS † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Ringworm NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Scabies † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Scrotal infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sepsis † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Septic shock † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Shingles † 1	4/357 (1.12%)	9/365 (2.47%)	0/7 (0.00%)
Sinus infection † 1	5/357 (1.40%)	12/365 (3.29%)	0/7 (0.00%)
Sinusitis † 1	29/357 (8.12%)	42/365 (11.51%)	1/7 (14.29%)
Skin infection † 1	12/357 (3.36%)	13/365 (3.56%)	0/7 (0.00%)
Soft tissue infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sporotrichosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Staphylococcal infection † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Stomach flu † 1	4/357 (1.12%)	2/365 (0.55%)	0/7 (0.00%)
Stomach virus † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Streptococcal sore throat † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Stye † 1	22/357 (6.16%)	11/365 (3.01%)	0/7 (0.00%)
Syphilis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Throat infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Thrush † 1	6/357 (1.68%)	13/365 (3.56%)	0/7 (0.00%)
Tinea capitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tinea corporis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tinea cruris † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tinea pedis † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Tongue infection † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Tonsillitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tooth abscess † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Tooth infection † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Tooth infection † 1	9/357 (2.52%)	8/365 (2.19%)	0/7 (0.00%)
Upper respiratory infection † 1	165/357 (46.22%)	180/365 (49.32%)	0/7 (0.00%)
Urinary infection † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Urinary tract infection † 1	26/357 (7.28%)	32/365 (8.77%)	0/7 (0.00%)
Urinary tract infection bacterial † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vaginal infection † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Viral gastroenteritis † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Viral infection † 1	6/357 (1.68%)	7/365 (1.92%)	0/7 (0.00%)
Viral laryngitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Viral meningitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Viral pharyngitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Viral pneumonia † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Viral syndrome † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Viral upper respiratory tract infection † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Wound infection † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Yeast infection † 1	3/357 (0.84%)	7/365 (1.92%)	0/7 (0.00%)
Injury, poisoning and procedural complications
Abrasions † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Alcohol intoxication † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Ankle fracture † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Ankle injury † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Arm fracture † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Arteriovenous fistula site oedema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Back injury † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Back strain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Broken bones † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Broken foot † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bruise † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Bruising † 1	18/357 (5.04%)	31/365 (8.49%)	0/7 (0.00%)
Bruising of face † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Bug bite † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Burn † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Burn of face, unspecified degree † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Collapsed vertebra † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Compression fracture † 1	0/357 (0.00%)	5/365 (1.37%)	0/7 (0.00%)
Contusion of finger † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Contusion of foot † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dermatitis radiation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dislocation of wrist † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dog bite † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Exposure to poison ivy † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Eye injury † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eyelid injury † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Face injury † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fall † 1	21/357 (5.88%)	30/365 (8.22%)	0/7 (0.00%)
Femur fracture † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fibula fracture † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Foot fracture † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Foot injury † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Foot sprain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Fracture † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fracture femur † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fracture of metacarpal bone(s) † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fracture of spine † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fracture vertebral † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fractured finger † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fractured metatarsal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Fractured radial head † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fractured ribs † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Fractured thumb † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fractured toe † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Fractured vertebra (compression) † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hand fracture † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Head injury † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hip fracture † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Injury to finger NOS † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Injury to shoulder NOS † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Insect bite NOS † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Knee derangement † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Knee injury † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Knee sprain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Laceration † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Laceration of arm † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Laceration of face † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Laceration of finger † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Laceration of foot † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Laceration of hand † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lateral epicondylitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Leg injury † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Lip injury † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Meniscus rupture † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mouth injury † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Muscle strain † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Neck strain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nose injury † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Penetrating abdominal trauma † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Penis injury † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Postoperative ileus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pulled muscle † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Puncture wound † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rib fracture † 1	2/357 (0.56%)	5/365 (1.37%)	0/7 (0.00%)
Rib injury † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Scalp laceration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Scratch † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Second rib fracture † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin abrasion † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Skin tear † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Spider bite † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Spinal compression fracture † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Spinal fracture † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Splinter † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sprained ankle † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Strain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Stress fracture † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Subdural hematoma † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sunburn † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Tennis elbow † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tick bite † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Toe injury † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Tongue injury † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Tooth fracture † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Tooth injury † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Tooth injury † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Torn muscle † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Transfusion reaction † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vascular access complication † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Wound † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Wound breakdown † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Wrist fracture † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Investigations
Absolute lymphocyte count decreased † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Absolute monocyte count decreased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Activated partial thromboplastin time prolonged † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Alanine aminotransferase decreased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Albumin decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Aspartate aminotransferase decreased † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Aspartate aminotransferase increased † 1	5/357 (1.40%)	4/365 (1.10%)	0/7 (0.00%)
Bilirubin total † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bilirubin total high † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bleeding time abnormal † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Blood albumin † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blood alkaline phosphatase NOS decreased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Blood bilirubin increased † 1	17/357 (4.76%)	13/365 (3.56%)	0/7 (0.00%)
Blood creatinine decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blood creatinine increased † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Blood in urine † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Blood phosphorus increased † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Blood urea nitrogen decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blood urea nitrogen increased † 1	1/357 (0.28%)	1/357 (0.28%)	0/7 (0.00%)
Bone density decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
BUN increased † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Calcium ionized † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Calcium low † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Carbon monoxide diffusing capacity decreased † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Chloride † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Chloride high † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cholesterol high † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Coronavirus test positive † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
CPK increase † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Creatine urine increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Creatinine increased † 1	24/357 (6.72%)	25/365 (6.85%)	1/7 (14.29%)
Cryoglobulins † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Decreased INR † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Disorder sperm † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Ejection fraction decreased † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Electrocardiogram QTc interval prolonged † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Elevated liver enzymes † 1	54/357 (15.13%)	56/365 (15.34%)	1/7 (14.29%)
Elevated prostate specific antigen [PSA] † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Exercise EKG abnormal † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Glucose high † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Glucose increased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
HbA1C increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Heart murmur † 1	1/357 (0.28%)	2/365 (0.55%)	1/7 (14.29%)
Heart rate high † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Heart rate increased † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Hematocrit increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
High cholesterol † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Increased serum creatinine † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
INR decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
INR increased † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Lactate dehydrogenase increased † 1	8/357 (2.24%)	4/365 (1.10%)	0/7 (0.00%)
Leukocyte count NOS † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lipase increased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Liver function test abnormal † 1	5/357 (1.40%)	10/365 (2.74%)	0/7 (0.00%)
Lymph node palpable † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lymphocytes † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Magnesium increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Mean cell volume low † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Norovirus test positive † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Phosphate decreased † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Phosphorus low † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Proteins serum plasma low † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Prothrombin increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Prothrombin time increased † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
PTH increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
QT interval prolonged † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Renal function decreased † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Serum ferritin abnormal † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
SGPT increased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin biopsy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sodium high † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sodium low † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sputum abnormal † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Systolic murmur † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Testosterone low † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Thyroid stimulating hormone increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Transaminases increased † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Transaminitis † 1	3/357 (0.84%)	6/365 (1.64%)	0/7 (0.00%)
Triglycerides † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
TSH increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Uric acid decreased † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Uric acid high † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Uric acid increased † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Urinary output diminished † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Urine color abnormal † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Urine output decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vitamin D decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Weight gain † 1	30/357 (8.40%)	21/365 (5.75%)	0/7 (0.00%)
Weight loss † 1	34/357 (9.52%)	28/365 (7.67%)	0/7 (0.00%)
White blood cell count increased † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Metabolism and nutrition disorders
Anorexia † 1	59/357 (16.53%)	78/365 (21.37%)	0/7 (0.00%)
Appetite increased † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Articular gout † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Copper deficiency † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Decreased appetite † 1	18/357 (5.04%)	21/365 (5.75%)	0/7 (0.00%)
Dehydration † 1	15/357 (4.20%)	32/365 (8.77%)	0/7 (0.00%)
Diabetes † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Electrolyte abnormality † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Fluid overload † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Folic acid deficiency † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gout † 1	4/357 (1.12%)	9/365 (2.47%)	0/7 (0.00%)
Gout flare † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Gouty pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hyperalbuminemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hypercalcemia † 1	7/357 (1.96%)	5/365 (1.37%)	0/7 (0.00%)
Hyperchloremic acidosis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hypercholesterolemia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hyperglycemia † 1	43/357 (12.04%)	38/365 (10.41%)	1/7 (14.29%)
Hyperkalemia † 1	6/357 (1.68%)	7/365 (1.92%)	0/7 (0.00%)
Hyperlipasemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hyperlipidemia † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hypermagnesemia † 1	5/357 (1.40%)	6/365 (1.64%)	0/7 (0.00%)
Hypernatremia † 1	1/357 (0.28%)	7/365 (1.92%)	0/7 (0.00%)
Hypertriglyceridemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hyperuricemia † 1	9/357 (2.52%)	9/365 (2.47%)	0/7 (0.00%)
Hypoalbuminemia † 1	17/357 (4.76%)	18/365 (4.93%)	0/7 (0.00%)
Hypocalcemia † 1	48/357 (13.45%)	54/365 (14.79%)	2/7 (28.57%)
Hypoglycemia † 1	11/357 (3.08%)	6/365 (1.64%)	0/7 (0.00%)
Hypokalemia † 1	85/357 (23.81%)	92/365 (25.21%)	1/7 (14.29%)
Hypomagnesemia † 1	34/357 (9.52%)	36/365 (9.86%)	0/7 (0.00%)
Hyponatremia † 1	28/357 (7.84%)	33/365 (9.04%)	1/7 (14.29%)
Hyponatremia aggravated † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hypophosphatemia † 1	62/357 (17.37%)	49/365 (13.42%)	0/7 (0.00%)
Hypouricaemia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hypovolemia † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Iron deficiency † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Malnutrition † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Oral intake reduced † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Protein-calorie malnutrition † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Type 2 diabetes mellitus † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vitamin B12 deficiency † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Vitamin D deficiency † 1	4/357 (1.12%)	12/365 (3.29%)	0/7 (0.00%)
Musculoskeletal and connective tissue disorders
Ache † 1	4/357 (1.12%)	5/365 (1.37%)	0/7 (0.00%)
Achilles tendon pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Achilles tendonitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Aching joints † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Arm discomfort † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Arthralgia † 1	34/357 (9.52%)	55/365 (15.07%)	0/7 (0.00%)
Arthritic pains † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Arthritis † 1	6/357 (1.68%)	2/365 (0.55%)	0/7 (0.00%)
Articular calcification † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Avascular necrosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Avascular necrosis femoral head † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Axillary lump † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Back discomfort † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Back muscle spasms † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Back pain † 1	147/357 (41.18%)	132/365 (36.16%)	0/7 (0.00%)
Back stiffness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Backache † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Baker's cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bone pain † 1	53/357 (14.85%)	52/365 (14.25%)	0/7 (0.00%)
Bone spur † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bursitis † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Buttock pain † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Calf pain † 1	2/357 (0.56%)	9/365 (2.47%)	0/7 (0.00%)
Cervical pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chest tenderness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chest wall pain † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Coccyalgia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Costochondritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Crackling jaw † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Cramps † 1	44/357 (12.32%)	47/365 (12.88%)	0/7 (0.00%)
Cramps in the calves † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Deformity thorax † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Degenerative disc disease † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Disorder tendon † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Elbow deformity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Fascitis plantar † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Fibromyalgia † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Finger cramps † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Fingers stiffness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Flank pain † 1	5/357 (1.40%)	8/365 (2.19%)	0/7 (0.00%)
Foot cramps † 1	6/357 (1.68%)	1/365 (0.27%)	0/7 (0.00%)
Foot discomfort † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Foot pain † 1	13/357 (3.64%)	13/365 (3.56%)	0/7 (0.00%)
Generalized muscle weakness † 1	2/357 (0.56%)	7/365 (1.92%)	0/7 (0.00%)
Gouty arthritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Groin discomfort † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Groin pain † 1	3/357 (0.84%)	7/365 (1.92%)	0/7 (0.00%)
Hand osteoarthritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hand pain † 1	5/357 (1.40%)	1/365 (0.27%)	0/7 (0.00%)
Hands weakness of † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Heaviness in limbs † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Hip discomfort † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Jaw bone pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Jaw disorder † 1	0/357 (0.00%)	5/365 (1.37%)	0/7 (0.00%)
Jaw movements disturbance † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Jaw pain † 1	17/357 (4.76%)	10/365 (2.74%)	0/7 (0.00%)
Joint ache † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Joint edema † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Joint effusion † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Joint inflammation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Joint stiffness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Leg cramps † 1	10/357 (2.80%)	13/365 (3.56%)	0/7 (0.00%)
Limb discomfort † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Limbs stiffness † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Localised muscle pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lower extremities weakness of † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lumbar disc degeneration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lumbar pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mobility decreased † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Muscle cramps † 1	38/357 (10.64%)	30/365 (8.22%)	0/7 (0.00%)
Muscle fatigue † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Muscle spasm † 1	6/357 (1.68%)	12/365 (3.29%)	0/7 (0.00%)
Muscle swelling † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Muscle tension † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Muscle twitching † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Muscle weakness † 1	13/357 (3.64%)	23/365 (6.30%)	0/7 (0.00%)
Musculoskeletal discomfort † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Musculoskeletal discomfort † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Musculoskeletal disorder † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Musculoskeletal pain † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Musculoskeletal stiffness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Myalgia † 1	51/357 (14.29%)	50/365 (13.70%)	0/7 (0.00%)
Neck discomfort † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Neck pain † 1	26/357 (7.28%)	37/365 (10.14%)	0/7 (0.00%)
Osteoarthritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Osteonecrosis of jaw † 1	12/357 (3.36%)	6/365 (1.64%)	0/7 (0.00%)
Osteoporosis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Pain back † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain bone † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain flank † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pain foot † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Pain foot † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pain groin † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pain in ankle † 1	0/357 (0.00%)	4/365 (1.10%)	0/7 (0.00%)
Pain in arm † 1	14/357 (3.92%)	12/365 (3.29%)	0/7 (0.00%)
Pain in elbow † 1	10/357 (2.80%)	4/365 (1.10%)	0/7 (0.00%)
Pain in extremity † 1	36/357 (10.08%)	33/365 (9.04%)	0/7 (0.00%)
Pain in fingers † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pain in hand † 1	4/357 (1.12%)	0/365 (0.00%)	0/7 (0.00%)
Pain in hip † 1	48/357 (13.45%)	32/365 (8.77%)	0/7 (0.00%)
Pain in jaw † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pain in joint † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pain in leg † 1	20/357 (5.60%)	21/365 (5.75%)	0/7 (0.00%)
Pain in legs † 1	17/357 (4.76%)	24/365 (6.58%)	0/7 (0.00%)
Pain in muscle † 1	12/357 (3.36%)	13/365 (3.56%)	0/7 (0.00%)
Pain in Neck † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Pain in shoulder † 1	40/357 (11.20%)	49/365 (13.42%)	0/7 (0.00%)
Pain in upper extremities † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Pain in wrist † 1	4/357 (1.12%)	8/365 (2.19%)	0/7 (0.00%)
Pain joint † 1	9/357 (2.52%)	12/365 (3.29%)	0/7 (0.00%)
Pain knee † 1	19/357 (5.32%)	17/365 (4.66%)	0/7 (0.00%)
Pain lower ribs † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pain sacroiliac † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Painful L arm † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pains in legs † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Plantar fasciitis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Popliteal cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Proximal myopathy † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pseudogout † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Psoriatic arthritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rhabdomyolysis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rib pain † 1	21/357 (5.88%)	24/365 (6.58%)	0/7 (0.00%)
Rotator cuff injury † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Rotator cuff tear † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Sacral pain † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Scapula pain † 1	5/357 (1.40%)	1/365 (0.27%)	0/7 (0.00%)
Sensation of heaviness † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Shin splints † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Shoulder blade pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Shoulder deformity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Soft tissue mass † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sore feet † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Spasms † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Stiff back † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Stiff neck † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Stiffness † 1	5/357 (1.40%)	9/365 (2.47%)	0/7 (0.00%)
Stiffness hip † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Stiffness shoulder † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Supraspinatus syndrome † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Swelling of knees † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Swelling of L knee † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Swelling of R knee † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Synovial cyst † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Temporomandibular joint disorder † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Tenderness † 1	1/357 (0.28%)	5/365 (1.37%)	0/7 (0.00%)
Tendinitis † 1	3/357 (0.84%)	2/365 (0.55%)	0/7 (0.00%)
Tenosynovitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Thoracic spondylosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tibia pain † 1	0/357 (0.00%)	4/365 (1.10%)	0/7 (0.00%)
Tightness of back muscles † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Torticollis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Trigger finger † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Trochanteric bursitis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Twitching † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Unilateral leg pain † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Upper back pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Weakness of arms † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Adenocarcinoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Adenocarcinoma of prostate † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Basal cell carcinoma † 1	4/357 (1.12%)	7/365 (1.92%)	0/7 (0.00%)
Bladder cancer † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Breast ductal carcinoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Carcinoma kidney † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
GI neoplasia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hemangioma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lip basal cell carcinoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lipoma † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Lung nodule † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Melanocytic nevus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Melanoma † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Morton's neuroma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Neoplasm † 1	0/357 (0.00%)	1/365 (0.27%)	1/7 (14.29%)
Neoplasm skin † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Nevus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nodular fasciitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Plantar warts † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Plasma cell leukemia † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Plasmacytoma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Prostate cancer † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Prostate cancer recurrent † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pyogenic granuloma † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rectal cancer † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Seborrheic keratosis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Second primary malignancy † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Skin cancer † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin carcinoma † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Squamous cell carcinoma † 1	12/357 (3.36%)	6/365 (1.64%)	0/7 (0.00%)
Thyroid hot nodule † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Thyroid nodular † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Thyroid nodule † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Thyroid nodule † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Uterine fibroid † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Verruca † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Wart † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Warts † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nervous system disorders
Abnormal sensation of limbs † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Ageusia † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Alertness decreased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Amnesia † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Ataxia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Attentiveness decreased † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Balance disorder † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Brain disorder NOS † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Burning leg † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Carpal tunnel syndrome † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Clonus † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cognitive deterioration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Cognitive disorder † 1	5/357 (1.40%)	6/365 (1.64%)	1/7 (14.29%)
Concentration impaired † 1	6/357 (1.68%)	7/365 (1.92%)	1/7 (14.29%)
Demyelinating polyneuropathy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Disorder equilibrium † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dizziness † 1	73/357 (20.45%)	91/365 (24.93%)	1/7 (14.29%)
Drowsiness † 1	5/357 (1.40%)	3/365 (0.82%)	0/7 (0.00%)
Dysesthesia † 1	3/357 (0.84%)	5/365 (1.37%)	0/7 (0.00%)
Dysgeusia † 1	51/357 (14.29%)	52/365 (14.25%)	0/7 (0.00%)
Dysosmia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dystonic reaction † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Electric shock sensation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Extremities burning sensation of † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Face rigidity † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Facial nerve disorder † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Faint † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Fine motor delay † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Foot drop † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Forgetfulness † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Head pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Head tightness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Headache † 1	87/357 (24.37%)	116/365 (31.78%)	1/7 (14.29%)
Hyperactivity † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hypersensation skin † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hypogeusia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Lethargy † 1	7/357 (1.96%)	9/365 (2.47%)	0/7 (0.00%)
Light headedness † 1	23/357 (6.44%)	24/365 (6.58%)	0/7 (0.00%)
Light-headed † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Localized tingling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Loss of consciousness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Memory impairment † 1	25/357 (7.00%)	27/365 (7.40%)	0/7 (0.00%)
Memory loss transient † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Mental concentration decreased † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Mental impairment † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Migraine † 1	4/357 (1.12%)	7/365 (1.92%)	0/7 (0.00%)
Nerve compression † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Nerve pain † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Nervous system disorder † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Neuralgia † 1	6/357 (1.68%)	3/365 (0.82%)	0/7 (0.00%)
Neuropathy † 1	52/357 (14.57%)	40/365 (10.96%)	0/7 (0.00%)
Numbness † 1	6/357 (1.68%)	7/365 (1.92%)	0/7 (0.00%)
Numbness facial † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Numbness in face † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Numbness localised † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Numbness localised † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Numbness of extremities † 1	8/357 (2.24%)	15/365 (4.11%)	0/7 (0.00%)
Numbness of upper arm † 1	1/357 (0.28%)	0/365 (0.00%)	1/7 (14.29%)
Optic neuritis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Paraesthesia hand † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Paresthesia † 1	54/357 (15.13%)	42/365 (11.51%)	0/7 (0.00%)
Paresthesia hand † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Paresthesia upper limb † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Parkinson's disease † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Post herpetic neuralgia † 1	1/357 (0.28%)	4/365 (1.10%)	0/7 (0.00%)
Presyncope † 1	9/357 (2.52%)	6/365 (1.64%)	0/7 (0.00%)
Psychomotor development impaired † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Radiculitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Radiculopathy † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Resting tremor † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Restless leg syndrome † 1	5/357 (1.40%)	5/365 (1.37%)	0/7 (0.00%)
Sciatica † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Seizure † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Sensory neuropathy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sensory peripheral neuropathy † 1	247/357 (69.19%)	232/365 (63.56%)	0/7 (0.00%)
Sinus headache † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sinus pain † 1	6/357 (1.68%)	3/365 (0.82%)	0/7 (0.00%)
Sleepiness † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Slurred speech † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Smell alteration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Somnolence † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Spasticity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Stroke † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Syncope † 1	8/357 (2.24%)	13/365 (3.56%)	0/7 (0.00%)
Taste alteration † 1	3/357 (0.84%)	12/365 (3.29%)	0/7 (0.00%)
Taste diminished † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Tension headaches † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tingling skin † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Transient ischemic attacks † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Tremor † 1	34/357 (9.52%)	32/365 (8.77%)	0/7 (0.00%)
Weakness left or right side † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pregnancy, puerperium and perinatal conditions
Pregnancy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Psychiatric disorders
Aggressive reaction † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Agitation † 1	6/357 (1.68%)	9/365 (2.47%)	0/7 (0.00%)
Altered mood † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Anxiety † 1	57/357 (15.97%)	71/365 (19.45%)	1/7 (14.29%)
Anxiety depression † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Confusion † 1	7/357 (1.96%)	4/365 (1.10%)	0/7 (0.00%)
Decreased activity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Delirium † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Delusional perception † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Depression † 1	38/357 (10.64%)	54/365 (14.79%)	0/7 (0.00%)
Disorientation † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Emotional disorder † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Emotional distress † 1	0/357 (0.00%)	0/365 (0.00%)	1/7 (14.29%)
Emotional instability † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Emotional lability † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Exaggerated well-being † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Grinding tooth † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hallucinations † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Insomnia † 1	136/357 (38.10%)	126/365 (34.52%)	0/7 (0.00%)
Lability emotional † 1	4/357 (1.12%)	3/365 (0.82%)	0/7 (0.00%)
Libido decreased † 1	3/357 (0.84%)	5/365 (1.37%)	0/7 (0.00%)
Mania † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Mental disorder NOS † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Mental distress † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Mental status changes † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Mood change † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Nightmares † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Panic attack † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Pseudoseizure † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Psychotic episode † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Restlessness † 1	0/357 (0.00%)	7/365 (1.92%)	0/7 (0.00%)
Sleep disorder † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Sleep disturbance † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Sleep walking † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Stress † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Suicidal ideation † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Transient insomnia † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Vivid dreams † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Renal and urinary disorders
Acute renal failure † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Acute renal insufficiency † 1	7/357 (1.96%)	10/365 (2.74%)	0/7 (0.00%)
Bed wetting † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bladder prolapse † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Bladder spasm † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Burning micturition † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Chronic kidney disease † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Chronic renal failure † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cloudy urine † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Continuous urinary leakage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Disorder urinary tract † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dysuria † 1	7/357 (1.96%)	12/365 (3.29%)	0/7 (0.00%)
Hematuria † 1	8/357 (2.24%)	13/365 (3.56%)	0/7 (0.00%)
Hemorrhagic cystitis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Incontinence † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Increased urinary frequency † 1	11/357 (3.08%)	17/365 (4.66%)	0/7 (0.00%)
Injury to kidney † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Kidney pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Kidney stones † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Lower urinary tract symptoms † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Micturition burning † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Nocturia † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Nocturia † 1	9/357 (2.52%)	11/365 (3.01%)	0/7 (0.00%)
Painful urination † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Polyuria † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Proteinuria † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Renal calculi † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Renal colic † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Renal disease † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Renal function aggravated † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Renal impairment † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Renal insufficiency † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Renal tract inflammation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Urethral burning on micturition † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Urgency urination † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Urinary hesitancy † 1	0/357 (0.00%)	3/365 (0.82%)	0/7 (0.00%)
Urinary incontinence † 1	6/357 (1.68%)	3/365 (0.82%)	0/7 (0.00%)
Urinary obstruction unspecified † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Urinary retention † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Urinary tract pain † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Urinary urgency † 1	2/357 (0.56%)	8/365 (2.19%)	0/7 (0.00%)
Urination difficulty † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Urination frequency of † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Urination pain † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Urine discoloration † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Reproductive system and breast disorders
Bartholin's cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Benign prostatic hyperplasia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bleeding menstrual heavy † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bloody semen † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Breast discomfort † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Breast lump † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Breast mass † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Breast pain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Breast swelling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Breast tenderness † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Cervical dysplasia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Enlarged prostate † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Epididymitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Erectile dysfunction † 1	9/357 (2.52%)	9/365 (2.47%)	0/7 (0.00%)
Genital abrasion † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Genital labial cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Genital lesion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Genital pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Gynecomastia † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Impotence † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Irregular menstruation † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Menorrhagia † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nipple discharge † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nipple tenderness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Paresthesia of genital female † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pelvic congestion syndrome † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pelvic pain † 1	4/357 (1.12%)	3/365 (0.82%)	0/7 (0.00%)
Peyronie's disease † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Premenstrual dysphoric disorder † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Prostatitis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Scrotal pain † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Scrotal swelling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Sexual dysfunction † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Spotting menstrual † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Spotting vaginal † 1	0/357 (0.00%)	5/365 (1.37%)	0/7 (0.00%)
Testicular disorder † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Testicular edema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Testicular pain † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Testis discomfort † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Uterine bleeding † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vaginal bleeding † 1	4/357 (1.12%)	3/365 (0.82%)	0/7 (0.00%)
Vaginal cyst † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vaginal discomfort † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vaginal dryness † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Vaginal inflammation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vaginal irritation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vaginal itching † 1	0/357 (0.00%)	6/365 (1.64%)	0/7 (0.00%)
Vaginal lesion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Vaginal pain † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Vulval lesion † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vulvovaginal atrophy † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Acute respiratory insufficiency † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Allergic rhinitis † 1	15/357 (4.20%)	23/365 (6.30%)	0/7 (0.00%)
Aspiration pneumonia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Asthma † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Atelectasis † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Bleeding nose † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Bleeding nose † 1	1/357 (0.28%)	5/365 (1.37%)	0/7 (0.00%)
Blistering of mouth † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Breath shortness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Breathing difficult † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Breathlessness † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bronchitis asthmatic † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Bronchospasm † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Choking † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Congestion nasal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
COPD exacerbation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cough † 1	118/357 (33.05%)	141/365 (38.63%)	1/7 (14.29%)
Cough nonproductive † 1	5/357 (1.40%)	2/365 (0.55%)	0/7 (0.00%)
Diaphragmatic disorder † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Difficulty breathing † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dry cough † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Dry nose † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dry throat † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Dyspnea † 1	109/357 (30.53%)	98/365 (26.85%)	1/7 (14.29%)
Epistaxis † 1	13/357 (3.64%)	11/365 (3.01%)	0/7 (0.00%)
Exacerbation of asthma † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Exertional dyspnea † 1	4/357 (1.12%)	1/365 (0.27%)	0/7 (0.00%)
Hemoptysis † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hemothorax † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hiccups † 1	14/357 (3.92%)	18/365 (4.93%)	0/7 (0.00%)
Hoarseness † 1	14/357 (3.92%)	14/365 (3.84%)	0/7 (0.00%)
Hypercapnia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hypoxemia † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hypoxia † 1	2/357 (0.56%)	10/365 (2.74%)	0/7 (0.00%)
Itchy throat † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Laryngeal erythema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Laryngospasm † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Nasal burning † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Nasal congestion † 1	52/357 (14.57%)	59/365 (16.16%)	0/7 (0.00%)
Nasal cyst † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Nasal irritation † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Nasal mucosal inflammation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Nasal sinus congestion † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Obstructive sleep apnea syndrome † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Organizing pneumonia † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Orthopnea † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Paranasal sinus hypersecretion † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Pharyngeal erythema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pharyngolaryngeal pain † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Phlegm † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pleural effusion † 1	3/357 (0.84%)	3/365 (0.82%)	0/7 (0.00%)
Pleuritic pain † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Postnasal drip † 1	8/357 (2.24%)	20/365 (5.48%)	0/7 (0.00%)
Productive cough † 1	7/357 (1.96%)	10/365 (2.74%)	0/7 (0.00%)
Pulmonary edema † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Pulmonary hypertension † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pulmonary infiltration † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Reactive airways disease † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Respiratory failure † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Rhinorrhea † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Rhinorrhea † 1	19/357 (5.32%)	21/365 (5.75%)	0/7 (0.00%)
Rhonchi † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Sinus congestion † 1	7/357 (1.96%)	23/365 (6.30%)	0/7 (0.00%)
Sinus disorder † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Sleep apnea † 1	6/357 (1.68%)	1/365 (0.27%)	0/7 (0.00%)
Sneezing † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Snoring † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sore throat † 1	34/357 (9.52%)	49/365 (13.42%)	0/7 (0.00%)
Sputum bloody † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tachypnea † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Throat irritation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Throat pain † 1	3/357 (0.84%)	10/365 (2.74%)	0/7 (0.00%)
Throat tightness † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Tracheal inflammation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Vocal cord nodule † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Voice alteration † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Wheezing † 1	9/357 (2.52%)	14/365 (3.84%)	0/7 (0.00%)
Skin and subcutaneous tissue disorders
Acne † 1	1/357 (0.28%)	4/365 (1.10%)	0/7 (0.00%)
Actinic keratosis † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Allergic rash † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Alopecia † 1	55/357 (15.41%)	23/365 (6.30%)	0/7 (0.00%)
Angioedema † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Atrophy skin † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Blister † 1	2/357 (0.56%)	4/365 (1.10%)	0/7 (0.00%)
Body odor † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Brittle nails † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Cherry angiomas † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Contact dermatitis † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Darkened skin † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Dermatitis † 1	4/357 (1.12%)	0/365 (0.00%)	0/7 (0.00%)
Diaphoresis † 1	9/357 (2.52%)	7/365 (1.92%)	0/7 (0.00%)
Discoloration skin † 1	1/357 (0.28%)	6/365 (1.64%)	0/7 (0.00%)
Drenching sweats † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
DRESS syndrome † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Dry skin † 1	52/357 (14.57%)	48/365 (13.15%)	0/7 (0.00%)
Eczema † 1	1/357 (0.28%)	4/365 (1.10%)	0/7 (0.00%)
Erythema † 1	5/357 (1.40%)	8/365 (2.19%)	0/7 (0.00%)
Erythropapular rash † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Excess sweating † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Extensive rash of forearm † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Facial swelling † 1	2/357 (0.56%)	3/365 (0.82%)	0/7 (0.00%)
Forehead swelling † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Goose bumps † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Granuloma faciale † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hair breakage † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hair loss † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Heat rash † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Hidradenitis † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Hirsutism † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Hives † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hyperhidrosis † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Hyperpigmentation skin † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Hyperpigmentation skin † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Ingrowing nail † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Ingrown toe nail † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Itchy rash † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Itchy scalp † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Keratosis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
LE rash † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Leg ulcer † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Localized rash † 1	1/357 (0.28%)	5/365 (1.37%)	0/7 (0.00%)
Loss of eyelashes † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Malar rash † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Nail discoloration † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Nail disorder † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Neck rash † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Night sweats † 1	15/357 (4.20%)	24/365 (6.58%)	0/7 (0.00%)
Palmar erythema † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Papule † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Petechiae † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Poison ivy rash † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Poison oak rash † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pruritis † 1	25/357 (7.00%)	40/365 (10.96%)	0/7 (0.00%)
Psoriasis † 1	2/357 (0.56%)	2/365 (0.55%)	0/7 (0.00%)
Purpura † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Rash acneiform † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Rash erythematous † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Rash erythematous † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Rash face † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Rash face † 1	3/357 (0.84%)	4/365 (1.10%)	0/7 (0.00%)
Rash follicular † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Rash maculo-papular † 1	113/357 (31.65%)	126/365 (34.52%)	1/7 (14.29%)
Rash over arms † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Rash pruritic † 1	7/357 (1.96%)	12/365 (3.29%)	0/7 (0.00%)
Rash scaly † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Rosacea † 1	5/357 (1.40%)	2/365 (0.55%)	0/7 (0.00%)
Scab † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Scabbing † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Scalp disorder † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Scalp pain † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Scalp plaque † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sebaceous cyst † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Seborrhea capitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Seborrheic dermatitis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin bleeding † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin cold clammy † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin disorder † 1	4/357 (1.12%)	0/365 (0.00%)	0/7 (0.00%)
Skin dry † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin fissures † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin hyperpigmentation † 1	5/357 (1.40%)	7/365 (1.92%)	0/7 (0.00%)
Skin hypopigmentation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin irritation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin lesion † 1	5/357 (1.40%)	9/365 (2.47%)	0/7 (0.00%)
Skin peeling † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Skin peeling † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Skin pigmentation † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin rash † 1	6/357 (1.68%)	2/365 (0.55%)	0/7 (0.00%)
Skin scaly † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin seborrheic † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin sensitization † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Skin sensitization † 1	3/357 (0.84%)	1/365 (0.27%)	0/7 (0.00%)
Skin striae † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin swelling † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Skin tenderness † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Skin ulcer † 1	3/357 (0.84%)	0/365 (0.00%)	0/7 (0.00%)
Solar dermatitis † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Subcutaneous nodule † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sun spots † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Sweating † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Sweating † 1	6/357 (1.68%)	10/365 (2.74%)	0/7 (0.00%)
Sweating and Sweaty † 1	0/357 (0.00%)	0/365 (0.00%)	0/7 (0.00%)
Sweating and Sweaty † 1	4/357 (1.12%)	9/365 (2.47%)	0/7 (0.00%)
Sweating increased † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Unspecified disease of hair and hair follicles † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Urticaria † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Urticaria localised † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Venous ulcer NOS † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Social circumstances
Caregiver † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Hearing disability † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Surgical and medical procedures
Catheter placement † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Correction hammer toe † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cyst removal † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Debridement † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Eye irrigation † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Eyelid abscess drainage † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Hip surgery † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Kyphoplasty † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Nasal sinus drainage † 1	4/357 (1.12%)	4/365 (1.10%)	0/7 (0.00%)
Root canal procedure † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Rotator cuff repair † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Surgical procedure † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Suture insertion † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Tooth extraction † 1	4/357 (1.12%)	3/365 (0.82%)	0/7 (0.00%)
Wound drainage † 1	2/357 (0.56%)	0/365 (0.00%)	0/7 (0.00%)
Vascular disorders
Aortic aneurysm † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Atherosclerosis † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Bleeding † 1	0/357 (0.00%)	2/365 (0.55%)	0/7 (0.00%)
Circulating thrombus † 1	1/357 (0.28%)	1/365 (0.27%)	0/7 (0.00%)
Cold extremities † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Cold feet † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Deep vein thrombosis † 1	10/357 (2.80%)	13/365 (3.56%)	0/7 (0.00%)
Essential hypertension † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Flushing † 1	8/357 (2.24%)	8/365 (2.19%)	1/7 (14.29%)
Hematoma † 1	7/357 (1.96%)	6/365 (1.64%)	0/7 (0.00%)
Hot flashes † 1	20/357 (5.60%)	27/365 (7.40%)	0/7 (0.00%)
Hypertension † 1	72/357 (20.17%)	69/365 (18.90%)	0/7 (0.00%)
Hypotension † 1	30/357 (8.40%)	47/365 (12.88%)	1/7 (14.29%)
Hypotension orthostatic † 1	2/357 (0.56%)	10/365 (2.74%)	0/7 (0.00%)
Hypotensive † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Lymphedema † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Orthostatic hypertension † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Pallor † 1	1/357 (0.28%)	2/365 (0.55%)	0/7 (0.00%)
Phlebitis superficial † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Pulmonary embolism † 1	0/357 (0.00%)	4/365 (1.10%)	0/7 (0.00%)
Superficial thrombophlebitis † 1	2/357 (0.56%)	1/365 (0.27%)	0/7 (0.00%)
Superficial thrombosis of veins † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Thromboembolic event † 1	9/357 (2.52%)	21/365 (5.75%)	0/7 (0.00%)
Thrombosis † 1	1/357 (0.28%)	3/365 (0.82%)	0/7 (0.00%)
Uncontrolled hypertension † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
Varicose vein † 1	0/357 (0.00%)	1/365 (0.27%)	0/7 (0.00%)
Varicosity † 1	1/357 (0.28%)	0/365 (0.00%)	0/7 (0.00%)
1 Term from vocabulary, CTCAE (4.0); † Indicates events were collected by systematic assessment

Limitations and Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.

Results Point of Contact

• Name/Title: Ajantha Nithi
• Organization: Dana-Farber Cancer Institute
• Phone: 857-215-2829
• EMail: ajantha_nithi@dfci.harvard.edu

Publications of Results:

Richardson PG, Jacobus SJ, Weller EA, Hassoun H, Lonial S, Raje NS, Medvedova E, McCarthy PL, Libby EN, Voorhees PM, Orlowski RZ, Anderson LD Jr, Zonder JA, Milner CP, Gasparetto C, Agha ME, Khan AM, Hurd DD, Gowin K, Kamble RT, Jagannath S, Nathwani N, Alsina M, Cornell RF, Hashmi H, Campagnaro EL, Andreescu AC, Gentile T, Liedtke M, Godby KN, Cohen AD, Openshaw TH, Pasquini MC, Giralt SA, Kaufman JL, Yee AJ, Scott E, Torka P, Foley A, Fulciniti M, Hebert K, Samur MK, Masone K, Maglio ME, Zeytoonjian AA, Nadeem O, Schlossman RL, Laubach JP, Paba-Prada C, Ghobrial IM, Perrot A, Moreau P, Avet-Loiseau H, Attal M, Anderson KC, Munshi NC; DETERMINATION Investigators. Triplet Therapy, Transplantation, and Maintenance until Progression in Myeloma. N Engl J Med. 2022 Jul 14;387(2):132-147. doi: 10.1056/NEJMoa2204925. Epub 2022 Jun 5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Parmar H, Vesole DH, Biran N. From VAD to VRD: Is Transplant Still Needed in the Upfront Setting of Myeloma? Cancer J. 2021 May-Jun 01;27(3):190-195. doi: 10.1097/PPO.0000000000000522.

• Responsible Party: Paul Richardson, MD, Dana-Farber Cancer Institute
• ClinicalTrials.gov Identifier: NCT01208662
• Other Study ID Numbers: 10-106
• First Submitted: September 23, 2010
• First Posted: September 24, 2010
• Results First Submitted: October 2, 2023
• Results First Posted: December 18, 2023
• Last Update Posted: December 18, 2023