Study of Lenalidomide and Dexamethasone With or Without Pembrolizumab (MK-3475) in Participants With Newly Diagnosed Treatment Naive Multiple Myeloma (MK-3475-185/KEYNOTE-185)

• ClinicalTrials.gov Identifier: NCT02579863
• Recruitment Status: Terminated
• First Posted: October 20, 2015
• Results First Posted: September 17, 2019
• Last Update Posted: July 20, 2021
• Sponsor: Merck Sharp & Dohme LLC
• Information provided by (Responsible Party): Merck Sharp & Dohme LLC

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Multiple Myeloma
• Interventions: Biological: Pembrolizumab; Drug: Lenalidomide; Drug: Dexamethasone
• Enrollment: 310

Participant Flow

Recruitment Details	This study was conducted at 140 centers in 15 countries. The database cutoff date was August 3, 2020.
Pre-assignment Details	Note: Due to administrative reasons (a noncompliant site), 2 participants in the Pembrolizumab plus SOC arm and one participant in the SOC arm, were recorded as "Ongoing in Trial" in the CSR Disposition Table and "Final Disposition Unknown" here.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Period Title: Overall Study
Started	156	154
Treated	154	148
Completed	0	0
Not Completed	156	154
Reason Not Completed
Final Disposition Unknown	2	1
Adverse Event	18	11
Death	31	29
Lost to Follow-up	2	1
Physician Decision	1	2
Screen Failure	0	2
Study Terminated at Selected Sites	82	88
Withdrawal by Subject	20	20

Baseline Characteristics

Arm/Group Title		Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone	Total
Arm/Group Description		Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Total of all reporting groups
Overall Number of Baseline Participants		156	154	310
Baseline Analysis Population Description		The analysis population included all randomized participants.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	156 participants	154 participants	310 participants
		74.4 (6.0)	74.3 (5.9)	74.3 (6.0)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	156 participants	154 participants	310 participants
	Female	85 54.5%	81 52.6%	166 53.5%
	Male	71 45.5%	73 47.4%	144 46.5%
Ethnicity (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	156 participants	154 participants	310 participants
	Hispanic or Latino	4 2.6%	4 2.6%	8 2.6%
	Not Hispanic or Latino	143 91.7%	136 88.3%	279 90.0%
	Unknown or Not Reported	9 5.8%	14 9.1%	23 7.4%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	156 participants	154 participants	310 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	27 17.3%	27 17.5%	54 17.4%
	Native Hawaiian or Other Pacific Islander	1 0.6%	0 0.0%	1 0.3%
	Black or African American	9 5.8%	3 1.9%	12 3.9%
	White	115 73.7%	121 78.6%	236 76.1%
	More than one race	1 0.6%	0 0.0%	1 0.3%
	Unknown or Not Reported	3 1.9%	3 1.9%	6 1.9%
International Stage (I, II, III). [1]; Measure Type: Number; Unit of measure: Participants	Number Analyzed	156 participants	154 participants	310 participants
Stage I		39	53	92
Stage II		70	66	136
Stage III		46	34	80
Missing		1	1	2
		[1] Measure Description: The International Staging System (ISS) defines the factors that influence patient survival. The system has 3 stages based on the measurement of serum albumin and the levels of serum β2-microglobulin (β2-M). Stage I: β2-M <3.5 mg/L with a serum albumin of 3.5 g/dL or more; Stage II: Either of these 2 criteria: β2-M between 3.5 mg/L and 5.5 mg/dL Albumin <3.5 g/dL; Stage III: β2-M >5.5 mg/L.

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) Evaluated According to the International Myeloma Working Group (IMWG) Response Criteria 2011 by Clinical Adjudication Committee (CAC) Blinded Central Review
Description	PFS was defined as the time from randomization to the first documented disease progression (events of new bone lesions, soft tissue plasmacytomas or an increase in existing lesions, or death due to any cause). The median PFS was calculated from the product-limit (Kaplan-Meier) method for censored data. Due to the small number of events, the tail of the estimated survival distribution was close to the median for both arms. The higher variability of the tail estimates resulted in observing the median estimate in the experimental arm but not in the standard of care arm even when number of events in 2 arms were similar. The database cutoff date was July 9, 2018.
Time Frame	Up to approximately 30 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	156	154
Median (95% Confidence Interval); Unit of Measure: Months
	19.6 [1]; (15.3 to NA)	NA [2]; (15.5 to NA)

[1]

Upper Limit could not be estimated due to an insufficient number of events by the date of data cutoff.

[2]

The Median was not reached, and the Upper Limit could not be estimated due to insufficient number of events by the date of data cutoff.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Lenalidomide + Dexamethasone, Lenolidomide + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.33475
	Comments	[Not Specified]
	Method	Log Rank
	Comments	One-sided p-value based on Stratified log-rank test.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.90
	Confidence Interval	(2-Sided) 95%; 0.56 to 1.45
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by Age (<75 years vs >= 75 years) and ISS stage (I or II vs. III).

2. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from randomization to death due to any cause. OS was calculated from the product-limit (Kaplan-Meier) method for censored data. Participants without documented death at the time of the final analysis were censored at the date of the last follow-up. This is an event-driven (events of death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). The database cutoff date was August 3, 2020.
Time Frame	Up to approximately 55 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	156	154
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (44.6 to NA)	NA [2]; (NA to NA)

[1]

The Median was not reached, and the Upper Limit could not be estimated due to insufficient number of events before the date of data cutoff.

[2]

The Median was not reached, and the Upper and Lower Limits could not be estimated due to insufficient number of events before the date of data cutoff.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Lenalidomide + Dexamethasone, Lenolidomide + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.83416
	Comments	[Not Specified]
	Method	Stratified log-rank test
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	1.22
	Confidence Interval	(2-Sided) 95%; 0.81 to 1.84
	Estimation Comments	Based on Cox regression model with treatment as a covariate stratified by "Age" (<75 years vs >= 75 years) and "ISS stage" (I or II vs. III).

3. Secondary Outcome

Title	Overall Response Rate (ORR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Description	ORR was based on participants who achieved at least a partial response (stringent complete response [sCR]+complete response [CR]+very good partial response [VGPR]+partial response [PR]) according to the IMWG. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; sCR=stringent complete response, CR as above PLUS normal serum free light-chain (FLC) assay ratio and absence of clonal cells in bone marrow by immunohistochemistry or immunofluorescence; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours. The data cutoff date was July 9, 2018.
Time Frame	Up to approximately 30 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	156	154
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	74.4; (66.8 to 81.0)	68.8; (60.9 to 76.0)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pembrolizumab + Lenalidomide + Dexamethasone, Lenolidomide + Dexamethasone
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Statistical Test of Hypothesis	P-Value	0.13102
	Comments	[Not Specified]
	Method	One-sided p-value for testing
	Comments	H0: difference in % =0 versus H1: difference in % > 0.
Method of Estimation	Estimation Parameter	Difference in % vs SOC
	Estimated Value	5.8
	Confidence Interval	(2-Sided) 95%; -4.3 to 15.8
	Estimation Comments	[Not Specified]
Other Statistical Analysis		Based on Miettinen & Nurminen method stratified by 'Age' (<75 years vs >= 75 years) and 'ISS stage' (I or II vs. III); If there were no participants in one of the treatment groups involved in a comparison for a particular stratum, then that stratum was excluded from the treatment comparison.

4. Secondary Outcome

Title	Duration of Response (DOR) Evaluated According to IMWG Response Criteria by CAC Blinded Central Review
Description	Response duration was defined as the time from first documented evidence of at least a partial response (sCR+CR+VGPR+PR]), until confirmed disease progression or death. DOR was calculated from product-limit (Kaplan-Meier) method for censored data. This is an event-driven (events of disease progression and death) outcome measure. At the time of data cut-off, there were an insufficient number of events from the censored data to be able to estimate certain parameters (e.g. medians). Full Range is the minimum and maximum of the observed duration of response. The data cutoff date was July 9, 2018.
Time Frame	Up to approximately 30 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants who demonstrated at least a partial response. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	116	106
Median (95% Confidence Interval); Unit of Measure: Months
	NA [1]; (NA to NA)	NA [1]; (NA to NA)

[1]

The Median was not reached, and the limits could not be estimated due to the lack of progressive disease by the time of last disease assessment.

5. Secondary Outcome

Title	Disease Control Rate (DCR) Evaluated According to the IMWG Response Criteria by CAC Blinded Central Review
Description	Disease control rate was defined as the percentage of participants who achieved confirmed sCR, CR, VGPR, PR, or have demonstrated SD for at least 12 weeks prior to any evidence of progression. CR = negative immunofixation of serum and urine AND disappearance of any soft tissue plasmacytomas AND <5% plasmacytomas in the bone marrow; VGPR = serum and urine M-component detectable by immunofixation but not on electrophoresis OR ≥ 90% reduction in serum M-component plus urine M-component <100 mg/24 hr; PR = ≥50% reduction of serum M-protein and reduction in 24-hour urinary M-protein by ≥90% or to <200 mg/24 hours; SD = not meeting the criteria for CR, VGPR, PR, or PD; PD = development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. Data cutoff date was July 9, 2018.
Time Frame	Up to approximately 30 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	156	154
Measure Type: Number; Number (95% Confidence Interval); Unit of Measure: Percentage of participants
	89.1; (83.1 to 93.5)	91.6; (86.0 to 95.4)

6. Secondary Outcome

Title	Second Progression Free Survival (PFS2)
Description	PFS2 was defined as the time from randomization to subsequent disease progression after initiation of new anti-cancer therapy, or death from any cause, whichever occurred first, by investigator assessment. PFS was assessed by Clinical Adjudication Committee (CAC) blinded central review according to the IMWG response criteria based on the development of new bone lesions or soft tissue plasmacytomas or on a definite increase in the size of existing bone lesions or soft tissue plasmacytomas. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.
Time Frame	Up to approximately 55 months

Outcome Measure Data

Analysis Population Description

The analysis population included all randomized participants. Participants were included in the treatment group to which they were randomized. PFS2 was not completed due to incomplete enrollment for a clinical hold and study cancellation.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	0	0

No data displayed because Outcome Measure has zero total analyzed.

7. Secondary Outcome

Title	Number of Participants Who Experienced One or More Adverse Events (AEs)
Description	An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020.
Time Frame	Up to approximately 55 months

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	154	148
Measure Type: Count of Participants; Unit of Measure: Participants
	152 98.7%	141 95.3%

8. Secondary Outcome

Title	Number of Participants Discontinuing Study Treatment Due to an AE
Description	An AE was defined as any unfavorable and unintended sign including an abnormal laboratory finding, symptom or disease associated with the use of a medical treatment or procedure, regardless of whether it was considered related to the medical treatment or procedure, that occurred during the course of the study. The database cutoff date was August 3, 2020.
Time Frame	Up to approximately 55 months

Outcome Measure Data

Analysis Population Description

The analysis population consisted of all randomized participants who received at least one dose of study treatment.

Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone	Lenolidomide + Dexamethasone
Arm/Group Description:	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.	Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
Overall Number of Participants Analyzed	154	148
Measure Type: Count of Participants; Unit of Measure: Participants
	44 28.6%	26 17.6%

Adverse Events

Time Frame	Up to approximately 55 months
Adverse Event Reporting Description	The All-Cause Mortality analysis used all randomized participants whereas adverse events were collected for all treated participants. Disease progression of cancer under study was not considered an adverse event (AE) unless related to study treatment. Medical Dictionary for Regulatory Activities (MedDRA) preferred terms Neoplasm progression, Malignant neoplasm progression and Disease progression not related to study treatment were excluded as AEs. The Database Cutoff Date was Aug. 3, 2020.
Arm/Group Title	Pembrolizumab + Lenalidomide + Dexamethasone		Lenolidomide + Dexamethasone
Arm/Group Description	Participants received pembrolizumab 200 mg intravenously (IV) on Day 1 of each 21-day cycle PLUS lenalidomide 25 mg orally (PO) on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.		Participants received lenalidomide 25 mg PO on Days 1 to 21 of each 21-day treatment cycle, and dexamethasone 40 mg PO on Days 1, 8, 15 and 22 of each 28-day cycle for up to 18 cycles.
All-Cause Mortality
	Pembrolizumab + Lenalidomide + Dexamethasone		Lenolidomide + Dexamethasone
	Affected / at Risk (%)		Affected / at Risk (%)
Total	51/156 (32.69%)		43/154 (27.92%)
Serious Adverse Events
	Pembrolizumab + Lenalidomide + Dexamethasone		Lenolidomide + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/154 (59.09%)		65/148 (43.92%)
Blood and lymphatic system disorders
Anaemia † 1	3/154 (1.95%)	3	5/148 (3.38%)	5
Cytopenia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Febrile neutropenia † 1	3/154 (1.95%)	3	3/148 (2.03%)	3
Neutropenia † 1	2/154 (1.30%)	3	0/148 (0.00%)	0
Thrombocytopenia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Cardiac disorders
Acute myocardial infarction † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Angina pectoris † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Atrial fibrillation † 1	4/154 (2.60%)	4	2/148 (1.35%)	2
Atrioventricular block complete † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Bradycardia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Cardiac arrest † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Cardiac failure † 1	2/154 (1.30%)	2	2/148 (1.35%)	2
Cardiac failure acute † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Cardiac failure congestive † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Cardio-respiratory arrest † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Cardiopulmonary failure † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Myocardial infarction † 1	0/154 (0.00%)	0	2/148 (1.35%)	2
Myocarditis † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Congenital, familial and genetic disorders
Fanconi syndrome † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Endocrine disorders
Adrenal insufficiency † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hyperthyroidism † 1	4/154 (2.60%)	4	0/148 (0.00%)	0
Hypothyroidism † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Inappropriate antidiuretic hormone secretion † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Secondary adrenocortical insufficiency † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Eye disorders
Cataract † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Gastrointestinal disorders
Colitis † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Colitis ischaemic † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Constipation † 1	5/154 (3.25%)	6	0/148 (0.00%)	0
Diarrhoea † 1	5/154 (3.25%)	5	1/148 (0.68%)	1
Dysphagia † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Gastrointestinal perforation † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Inguinal hernia strangulated † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Intestinal ischaemia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Ischaemic enteritis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Large intestine perforation † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Nausea † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Odynophagia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pancreatitis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pancreatitis acute † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Rectal haemorrhage † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Upper gastrointestinal haemorrhage † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Vomiting † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
General disorders
Asthenia † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Chest pain † 1	1/154 (0.65%)	1	3/148 (2.03%)	3
Death † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Hypothermia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Influenza like illness † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Malaise † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Oedema peripheral † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Pain † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pyrexia † 1	8/154 (5.19%)	9	1/148 (0.68%)	1
Sudden death † 1	1/154 (0.65%)	1	2/148 (1.35%)	2
Hepatobiliary disorders
Cholecystitis acute † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Drug-induced liver injury † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hepatic failure † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hepatic function abnormal † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Hepatitis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Infections and infestations
Abscess jaw † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Arthritis infective † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Bacteraemia † 1	1/154 (0.65%)	2	0/148 (0.00%)	0
Bronchitis † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Bronchitis bacterial † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Cellulitis † 1	2/154 (1.30%)	2	1/148 (0.68%)	1
Clostridium difficile colitis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Diverticulitis † 1	3/154 (1.95%)	4	0/148 (0.00%)	0
Fungaemia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Gastroenteritis † 1	1/154 (0.65%)	2	0/148 (0.00%)	0
Influenza † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Klebsiella sepsis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Lower respiratory tract infection † 1	3/154 (1.95%)	4	1/148 (0.68%)	1
Neutropenic sepsis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Oesophageal candidiasis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Osteomyelitis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Peritonitis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Pneumonia † 1	16/154 (10.39%)	19	10/148 (6.76%)	10
Pneumonia cytomegaloviral † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pneumonia pneumococcal † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pneumonia respiratory syncytial viral † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Pulmonary sepsis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pulmonary tuberculosis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pyelonephritis † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Respiratory tract infection † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Sepsis † 1	8/154 (5.19%)	8	4/148 (2.70%)	4
Septic shock † 1	2/154 (1.30%)	2	2/148 (1.35%)	2
Sinusitis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Skin infection † 1	1/154 (0.65%)	2	0/148 (0.00%)	0
Subcutaneous abscess † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Upper respiratory tract infection † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Urinary tract infection † 1	2/154 (1.30%)	2	2/148 (1.35%)	2
Urosepsis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Injury, poisoning and procedural complications
Accidental overdose † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Femoral neck fracture † 1	0/154 (0.00%)	0	2/148 (1.35%)	2
Femur fracture † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Infusion related reaction † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pelvic fracture † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Rib fracture † 1	1/154 (0.65%)	1	2/148 (1.35%)	2
Spinal compression fracture † 1	0/154 (0.00%)	0	3/148 (2.03%)	3
Spinal fracture † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Subdural haematoma † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Synovial rupture † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Investigations
Blood bilirubin increased † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Blood creatinine increased † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Liver function test abnormal † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Neutrophil count decreased † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Transaminases increased † 1	3/154 (1.95%)	3	0/148 (0.00%)	0
Troponin increased † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Metabolism and nutrition disorders
Decreased appetite † 1	2/154 (1.30%)	2	1/148 (0.68%)	1
Dehydration † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Electrolyte imbalance † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Fulminant type 1 diabetes mellitus † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hypercalcaemia † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Hyperglycaemia † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Hyperkalaemia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hypocalcaemia † 1	2/154 (1.30%)	2	1/148 (0.68%)	1
Hypoglycaemia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hypokalaemia † 1	1/154 (0.65%)	1	2/148 (1.35%)	3
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/154 (0.65%)	1	3/148 (2.03%)	3
Back pain † 1	3/154 (1.95%)	3	3/148 (2.03%)	3
Intervertebral disc protrusion † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Neck pain † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pain in extremity † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Rhabdomyolysis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Torticollis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Pancreatic carcinoma † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Squamous cell carcinoma † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Tumour pain † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Nervous system disorders
Aphasia † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Brain injury † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Dizziness † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Encephalopathy † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Epilepsy † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Headache † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Lethargy † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Myasthenia gravis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Peripheral motor neuropathy † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Presyncope † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Syncope † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Transient ischaemic attack † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Dementia Alzheimer's type † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Psychiatric disorders
Anxiety † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Completed suicide † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Confusional state † 1	0/154 (0.00%)	0	1/148 (0.68%)	2
Delirium † 1	1/154 (0.65%)	1	1/148 (0.68%)	1
Psychotic disorder † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Suicide attempt † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Renal and urinary disorders
Acute kidney injury † 1	6/154 (3.90%)	6	2/148 (1.35%)	2
Renal failure † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Renal impairment † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Renal injury † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Urinary retention † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Respiratory, thoracic and mediastinal disorders
Acute respiratory failure † 1	2/154 (1.30%)	2	1/148 (0.68%)	1
Bronchitis chronic † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Chronic obstructive pulmonary disease † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Cough † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Dyspnoea † 1	3/154 (1.95%)	4	2/148 (1.35%)	2
Epistaxis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Hypoxia † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Pneumonia aspiration † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Pneumonitis † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Pulmonary embolism † 1	8/154 (5.19%)	8	0/148 (0.00%)	0
Pulmonary oedema † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Respiratory arrest † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Respiratory failure † 1	0/154 (0.00%)	0	2/148 (1.35%)	2
Skin and subcutaneous tissue disorders
Dermatitis exfoliative generalised † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Rash † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Rash erythematous † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Rash maculo-papular † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Skin ulcer † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Stevens-Johnson syndrome † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Vascular disorders
Aortic aneurysm † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Deep vein thrombosis † 1	2/154 (1.30%)	2	0/148 (0.00%)	0
Hypertension † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Hypertensive crisis † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
Hypotension † 1	1/154 (0.65%)	1	3/148 (2.03%)	3
Orthostatic hypotension † 1	1/154 (0.65%)	1	0/148 (0.00%)	0
Venous thrombosis limb † 1	0/154 (0.00%)	0	1/148 (0.68%)	1
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pembrolizumab + Lenalidomide + Dexamethasone		Lenolidomide + Dexamethasone
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	143/154 (92.86%)		129/148 (87.16%)
Blood and lymphatic system disorders
Anaemia † 1	32/154 (20.78%)	48	27/148 (18.24%)	40
Neutropenia † 1	30/154 (19.48%)	54	26/148 (17.57%)	51
Thrombocytopenia † 1	12/154 (7.79%)	16	12/148 (8.11%)	19
Endocrine disorders
Hypothyroidism † 1	13/154 (8.44%)	13	1/148 (0.68%)	1
Eye disorders
Vision blurred † 1	11/154 (7.14%)	12	3/148 (2.03%)	3
Gastrointestinal disorders
Abdominal pain † 1	13/154 (8.44%)	16	13/148 (8.78%)	18
Constipation † 1	55/154 (35.71%)	62	33/148 (22.30%)	35
Diarrhoea † 1	36/154 (23.38%)	51	34/148 (22.97%)	48
Dry mouth † 1	12/154 (7.79%)	13	5/148 (3.38%)	5
Dyspepsia † 1	8/154 (5.19%)	9	2/148 (1.35%)	2
Nausea † 1	37/154 (24.03%)	54	33/148 (22.30%)	38
Stomatitis † 1	9/154 (5.84%)	11	6/148 (4.05%)	6
Vomiting † 1	30/154 (19.48%)	39	9/148 (6.08%)	16
General disorders
Asthenia † 1	11/154 (7.14%)	11	17/148 (11.49%)	20
Fatigue † 1	44/154 (28.57%)	52	37/148 (25.00%)	39
Oedema † 1	8/154 (5.19%)	8	6/148 (4.05%)	7
Oedema peripheral † 1	25/154 (16.23%)	31	27/148 (18.24%)	28
Pyrexia † 1	29/154 (18.83%)	41	10/148 (6.76%)	11
Infections and infestations
Bronchitis † 1	9/154 (5.84%)	12	4/148 (2.70%)	5
Nasopharyngitis † 1	11/154 (7.14%)	16	11/148 (7.43%)	13
Oral candidiasis † 1	15/154 (9.74%)	16	2/148 (1.35%)	2
Pneumonia † 1	11/154 (7.14%)	11	2/148 (1.35%)	2
Upper respiratory tract infection † 1	16/154 (10.39%)	16	13/148 (8.78%)	17
Urinary tract infection † 1	15/154 (9.74%)	16	12/148 (8.11%)	16
Injury, poisoning and procedural complications
Contusion † 1	2/154 (1.30%)	3	8/148 (5.41%)	10
Fall † 1	7/154 (4.55%)	10	9/148 (6.08%)	12
Investigations
Alanine aminotransferase increased † 1	11/154 (7.14%)	11	3/148 (2.03%)	3
Aspartate aminotransferase increased † 1	8/154 (5.19%)	8	1/148 (0.68%)	1
Neutrophil count decreased † 1	13/154 (8.44%)	23	12/148 (8.11%)	23
Weight decreased † 1	10/154 (6.49%)	10	17/148 (11.49%)	18
Metabolism and nutrition disorders
Decreased appetite † 1	26/154 (16.88%)	28	19/148 (12.84%)	21
Dehydration † 1	8/154 (5.19%)	14	5/148 (3.38%)	6
Gout † 1	8/154 (5.19%)	14	4/148 (2.70%)	5
Hyperglycaemia † 1	10/154 (6.49%)	17	8/148 (5.41%)	12
Hypocalcaemia † 1	16/154 (10.39%)	18	8/148 (5.41%)	9
Hypokalaemia † 1	26/154 (16.88%)	31	17/148 (11.49%)	21
Hypomagnesaemia † 1	10/154 (6.49%)	10	5/148 (3.38%)	6
Hyponatraemia † 1	9/154 (5.84%)	10	1/148 (0.68%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	17/154 (11.04%)	21	9/148 (6.08%)	12
Back pain † 1	20/154 (12.99%)	24	17/148 (11.49%)	21
Muscle spasms † 1	14/154 (9.09%)	17	14/148 (9.46%)	16
Muscular weakness † 1	11/154 (7.14%)	12	4/148 (2.70%)	5
Musculoskeletal chest pain † 1	11/154 (7.14%)	11	7/148 (4.73%)	7
Musculoskeletal pain † 1	11/154 (7.14%)	14	10/148 (6.76%)	11
Pain in extremity † 1	9/154 (5.84%)	11	8/148 (5.41%)	10
Nervous system disorders
Dizziness † 1	14/154 (9.09%)	15	14/148 (9.46%)	15
Dysgeusia † 1	8/154 (5.19%)	8	12/148 (8.11%)	12
Headache † 1	9/154 (5.84%)	9	11/148 (7.43%)	14
Neuropathy peripheral † 1	9/154 (5.84%)	11	12/148 (8.11%)	13
Tremor † 1	11/154 (7.14%)	11	16/148 (10.81%)	16
Psychiatric disorders
Anxiety † 1	12/154 (7.79%)	14	11/148 (7.43%)	12
Depression † 1	9/154 (5.84%)	10	8/148 (5.41%)	8
Insomnia † 1	22/154 (14.29%)	25	27/148 (18.24%)	33
Respiratory, thoracic and mediastinal disorders
Cough † 1	20/154 (12.99%)	21	18/148 (12.16%)	19
Dysphonia † 1	3/154 (1.95%)	6	10/148 (6.76%)	10
Dyspnoea † 1	19/154 (12.34%)	21	12/148 (8.11%)	12
Epistaxis † 1	8/154 (5.19%)	8	6/148 (4.05%)	6
Oropharyngeal pain † 1	8/154 (5.19%)	10	5/148 (3.38%)	5
Skin and subcutaneous tissue disorders
Dry skin † 1	9/154 (5.84%)	9	3/148 (2.03%)	3
Night sweats † 1	8/154 (5.19%)	10	5/148 (3.38%)	5
Pruritus † 1	13/154 (8.44%)	17	5/148 (3.38%)	5
Rash † 1	32/154 (20.78%)	45	19/148 (12.84%)	20
Rash maculo-papular † 1	14/154 (9.09%)	19	11/148 (7.43%)	13
Vascular disorders
Hypotension † 1	12/154 (7.79%)	13	8/148 (5.41%)	9
1 Term from vocabulary, MedDRA 23.0; † Indicates events were collected by systematic assessment

Limitations and Caveats

The MK-3475-185 study was stopped/terminated early. Endpoint statistics may be biased due to the incomplete treatment and follow-up of participants after study termination

More Information

Certain Agreements

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

There IS 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.

The sponsor must have the opportunity to review all proposed abstracts, manuscripts or presentations regarding this trial 45 days prior to submission for publication/presentation. Any information identified by the sponsor as confidential must be deleted prior to submission; this confidentiality does not include efficacy and safety results. Sponsor review can be expedited to meet publication timelines.

Results Point of Contact

• Name/Title: Senior Vice President, Global Clinical Development
• Organization: Merck Sharp & Dohme Corp.
• Phone: 1-800-672-6372
• EMail: ClinicalTrialsDisclosure@merck.com

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

Usmani SZ, Schjesvold F, Oriol A, Karlin L, Cavo M, Rifkin RM, Yimer HA, LeBlanc R, Takezako N, McCroskey RD, Lim ABM, Suzuki K, Kosugi H, Grigoriadis G, Avivi I, Facon T, Jagannath S, Lonial S, Ghori RU, Farooqui MZH, Marinello P, San-Miguel J; KEYNOTE-185 Investigators. Pembrolizumab plus lenalidomide and dexamethasone for patients with treatment-naive multiple myeloma (KEYNOTE-185): a randomised, open-label, phase 3 trial. Lancet Haematol. 2019 Sep;6(9):e448-e458. doi: 10.1016/S2352-3026(19)30109-7. Epub 2019 Jul 18.

• Responsible Party: Merck Sharp & Dohme LLC
• ClinicalTrials.gov Identifier: NCT02579863
• Other Study ID Numbers: 3475-185; 2015-002901-12 ( EudraCT Number ); 163239 ( Registry Identifier: JAPIC-CTI ); MK-3475-185 ( Other Identifier: Merck ); KEYNOTE-185 ( Other Identifier: Merck )
• First Submitted: October 16, 2015
• First Posted: October 20, 2015
• Results First Submitted: June 7, 2019
• Results First Posted: September 17, 2019
• Last Update Posted: July 20, 2021