Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (ICARIA-MM)

• ClinicalTrials.gov Identifier: NCT02990338
• Recruitment Status: Completed
• First Posted: December 13, 2016
• Results First Posted: December 6, 2019
• Last Update Posted: November 18, 2023
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: None (Open Label); Primary Purpose: Treatment
• Condition: Plasma Cell Myeloma
• Interventions: Drug: Isatuximab; Drug: Pomalidomide; Drug: Dexamethasone
• Enrollment: 307

Participant Flow

Recruitment Details

The study was conducted at 102 sites in 24 countries. A total of 387 participants were screened between 22 December 2016 and 01 February 2018. Out of which, 307 participants were randomized in 1:1 ratio to IPd (Isatuximab + Pomalidomide + Dexamethasone) and Pd (Pomalidomide + Dexamethasone) arms using an interactive response technology (IRT).

Pre-assignment Details

Randomization was stratified by age (less than [<] 75 years versus greater than and equal to [>=] 75 years) and number of previous lines of therapy (2 or 3 versus more than 3). The current results are updated to report the final OS analysis and safety and participant flow data based on a data cut-off date of 14 March 2022. A few participants are still on treatment in the Pd and IPd arm who are being monitored for safety assessments.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 milligrams (mg) Per os (PO) on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 241.6 weeks).	Participants received isatuximab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 245.6 weeks).
Period Title: Overall Study
Started	153	154
Treated	149	152
Completed	123	118
Not Completed	30	36
Reason Not Completed
Ongoing	30	36

Baseline Characteristics

Arm/Group Title		Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)	Total
Arm/Group Description		Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 241.6 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 245.6 weeks).	Total of all reporting groups
Overall Number of Baseline Participants		153	154	307
Baseline Analysis Population Description		Analysis was performed on randomized population which included all participants with a signed informed consent and have been allocated a randomization number by the IRT, regardless of whether the participants was treated or not.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	153 participants	154 participants	307 participants
		65.2 (9.5)	66.6 (9.1)	65.9 (9.3)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	153 participants	154 participants	307 participants
	Female	83 54.2%	65 42.2%	148 48.2%
	Male	70 45.8%	89 57.8%	159 51.8%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	153 participants	154 participants	307 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	15 9.8%	21 13.6%	36 11.7%
	Native Hawaiian or Other Pacific Islander	1 0.7%	2 1.3%	3 1.0%
	Black or African American	3 2.0%	1 0.6%	4 1.3%
	White	126 82.4%	118 76.6%	244 79.5%
	More than one race	0 0.0%	0 0.0%	0 0.0%
	Unknown or Not Reported	8 5.2%	12 7.8%	20 6.5%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS)
Description	PFS:time from date of randomization to date of first documentation of progressive disease (PD) determined by Independent Response Committee (IRC) or date of death from any cause, whichever comes first. If progression or death was not observed, participant was censored at date of last progression-free tumor assessment prior to study cut-off date. Analysis was performed by Kaplan-Meier method. PD as per International Myeloma Working Group (IMWG) criteria was defined as increase of >=25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be >=0.5gram(g)/dL), serum M-protein increase >=1g/dL if lowest M component was >=5g/dL; urine M-component (absolute increase must be >=200mg/24hour), appearance of new lesion(s),>=50% increase from nadir in sum of the products of the maximal perpendicular diameters of measured lesions (SPD) of >1 lesion, or >=50% increase in the longest diameter of a previous lesion >1 centimeter in short axis.
Time Frame	From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intent-to-treat (ITT) population which included all randomized participants.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Median (95% Confidence Interval); Unit of Measure: months
	6.47; (4.468 to 8.279)	11.53; (8.936 to 13.897)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pd (Pomalidomide + Dexamethasone), IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Comments	Confidence interval (CI) for Kaplan-Meier estimates were calculated with log-log transformation of survival function and methods of Brookmeyer and Crowley.
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the type I error rate meaning no further testing would be performed unless the significance level had been reached on PFS.
Statistical Test of Hypothesis	P-Value	0.0005
	Comments	One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.025.
	Method	Log Rank
	Comments	Stratification was based on age (<75 years versus >=75 years) and number of previous lines of therapy (2 or 3 versus >3) according to IRT.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.596
	Confidence Interval	(2-Sided) 95%; 0.436 to 0.814
	Estimation Comments	Stratification was based on age (<75 years versus >=75 years) and number of previous lines of therapy (2 or 3 versus >3) according to IRT.

2. Secondary Outcome

Title	Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC)
Description	ORR (IMWG criteria): percentage of participants with stringent complete response(sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) as best overall response, assessed by IRC. sCR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates plus normal free light chain(FLC)ratio(0.26-1.65), absence of clonal cells in bone marrow biopsy.CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.VGPR: serum and urine M-protein detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h/,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h,if present at baseline,>=50% reduction in the size (SPD) of soft tissue plasmacytomas.
Time Frame	From the date of randomization to the date of first documentation of progression or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Measure Type: Number; Unit of Measure: percentage of participants
	35.3	60.4

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pd (Pomalidomide + Dexamethasone), IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the type I error rate meaning no further testing would be performed unless the significance level had been reached on PFS.
Statistical Test of Hypothesis	P-Value	<0.0001
	Comments	Threshold for statistical significance at 0.025.
	Method	Cochran-Mantel-Haenszel
	Comments	One sided p-value was stratified based on age (<75 years versus >=75 years) and number of previous lines (2 or 3 versus >3) according to IRT.

3. Secondary Outcome

Title	Percentage of Participants With Best Overall Response (BOR) as Per Independent Response Committee
Description	BOR:best sequential response from start of treatment until disease progression, death, initiation of further anti-myeloma treatment/data cut-off, whichever comes first. Ordering of evaluations from best to worse was: sCR,CR,VGPR,PR, minimal response (MR), stable disease (SD), PD, and not evaluable.CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates. sCR:CR as defined previously plus normal FLC ratio (0.26 to 1.65), absence of clonal cells in bone marrow biopsy. VGPR: serum and urine M-protein detectable by immunofixation,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h. MR:>=25% but <=49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%. SD: Not meeting criteria for CR,VGPR,PR,MR/PD.
Time Frame	From the date of randomization until disease progression, or death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Measure Type: Number; Unit of Measure: percentage of participants
Stringent complete response	0.7	0
Complete response	1.3	4.5
Very good partial response	6.5	27.3
Partial response	26.8	28.6
Minimal response	11.1	6.5
Stable disease	29.4	21.4
Progressive Disease	9.2	3.9
Not evaluable	10.5	4.5

4. Secondary Outcome

Title	Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee
Description	VGPR rate was defined as the percentage of participants achieving a VGPR or better as BOR. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h or >=90% decrease in the sum of maximal perpendicular diameter compared to baseline in soft tissue plasmacytoma. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.
Time Frame	From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment, or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Measure Type: Number; Unit of Measure: percentage of participants
	8.5	31.8

5. Secondary Outcome

Title	Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee
Description	CBR was defined as the percentage of participants achieving a MR or better as BOR. MR was defined as >= 25% but <= 49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%, which still exceed 200 mg/24h; if present at baseline, >=50% reduction in size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first.
Time Frame	From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Measure Type: Number; Unit of Measure: percentage of participants
	46.4	66.9

6. Secondary Outcome

Title	Overall Survival (OS): Final Analysis
Description	OS was defined as the time from the date of randomization to death from any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive or at the cut-off date, whichever comes first. This pre-specified final analysis was performed when the 220 OS events were met.
Time Frame	From the date of randomization to date of death from any cause or data cut-off date, whichever was earlier (maximum duration 245.6 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 241.6 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 245.6 weeks).
Overall Number of Participants Analyzed	153	154
Median (95% Confidence Interval); Unit of Measure: months
	17.71; (14.390 to 26.218)	24.57; (20.304 to 31.310)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pd (Pomalidomide + Dexamethasone), IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the type I error rate meaning no further testing would be performed unless the significance level had been reached on PFS.
Statistical Test of Hypothesis	P-Value	0.0319
	Comments	One-sided significance level was 0.02 using the O'Brien-Fleming alpha spending function.
	Method	Log Rank
	Comments	Stratified on age (<75 years versus >=75 years) and number of previous lines of therapy (2 or 3 versus > 3) according to IRT.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.776
	Confidence Interval	(2-Sided) 95%; 0.594 to 1.015
	Estimation Comments	Stratified on age (<75 years versus >=75 years) and number of previous lines of therapy (2 or 3 versus > 3) according to IRT.

7. Secondary Outcome

Title	Time to Progression (TTP) as Per Independent Response Committee
Description	TTP was defined as time from randomization to the date of first documentation of PD, as determined by the IRC. As per IMWG criteria, PD was defined for participants with increase of >= 25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be >= 0.5 g/dL), serum M-protein increase >=1 g/dL if the lowest M component was >=5 g/dL; urine M-component (the absolute increase must be >=200 mg/24hour), appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion, or >=50% increase in the longest diameter of a previous lesion >1 centimeter in short axis.
Time Frame	From the date of randomization to the date of first documentation of progression, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Median (95% Confidence Interval); Unit of Measure: months
	7.75; (5.027 to 9.758)	12.71; (11.203 to 15.211)

8. Secondary Outcome

Title	Progression Free Survival in High Risk Cytogenetic Population
Description	PFS in high risk cytogenetic population was defined as PFS in subgroup of participants carrying high risk cytogenetic changes including del(17p), translocation (t)(4;14) or translocation t(14;16) assessed by fluorescence in situ hybridization (FISH). PFS was defined as the time from date of randomization to date of first documentation of PD (determined by IRC) or date of death from any cause, whichever comes first. PD defined as per IMWG criteria as: increase of >=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be >=0.5 g/dL), serum M-protein increase >=1 g/dL if lowest M component was >=5 g/dL; urine M-component (absolute increase must be >=200 mg/24hour), appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion, or >=50% increase in the longest diameter of previous lesion >1 centimeter (cm) in short axis.
Time Frame	From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed in high-risk cytogenetic population which included participants carrying del (17p), t(4;14) or t(14;16) in each arm.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	36	25
Median (95% Confidence Interval); Unit of Measure: months
	3.745; (2.793 to 7.885)	7.491 [1]; (2.628 to NA)

[1]

Due to smaller number of participants with an event, 95% CI could not be calculated.

9. Secondary Outcome

Title	Duration of Response (DOR) as Per Independent Response Committee
Description	DOR:time from date of first IRC determined response(PR or better) to date of first IRC-PD or death, whichever occurred first.DOR was determined only for participants who had achieved a response of PR or better based on disease assessment by IRC.If progression or death was not observed,participant was censored at date of participants last progression-free tumor assessment prior to initiation of further anti-myeloma treatment(if any)and study cut-off date. PD(IMWG criteria):increase of >=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be >=0.5 g/dL), serum M-protein increase >=1g/dL if lowest M component was >=5g/dL;urine M-component (absolute increase must be >=200mg/24 hour),appearance of new lesion(s), >=50% increase from nadir in SPD of >1 lesion,or >=50% increase in the longest diameter of a previous lesion >1 cm in short axis. PR:>=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h.
Time Frame	From the date of the first IRC determined response to the date of first IRC progression or death, whichever occurred first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on responders in ITT population. Here, 'overall number of participants analyzed' = participants evaluable for this outcome measure.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	54	93
Median (95% Confidence Interval); Unit of Measure: months
	11.07 [1]; (8.542 to NA)	13.27 [1]; (10.612 to NA)

[1]

Due to smaller number of participants with an event, 95% CI could not be calculated.

10. Secondary Outcome

Title	Time to First Response (TT1R) as Per Independent Response Committee
Description	TT1R was defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. PR was defined as >=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >=90% or to <200 mg/24 h. In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.
Time Frame	From the date of randomization to the date of first IRC determined response, or death or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Median (95% Confidence Interval); Unit of Measure: months
	3.02; (2.825 to 5.060)	1.94; (1.314 to 2.004)

11. Secondary Outcome

Title	Time to Best Response (TTBR) as Per Independent Response Committee
Description	TTBR was defined as the time from randomization to the date of first occurrence of IRC determined BOR (PR or better) that was subsequently confirmed. PR was defined as >=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by >=90% or to <200 mg/24 h. In addition to the above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first.
Time Frame	From the date of randomization to date of first occurrence of IRC determined best overall response or data cut-off whichever comes first (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	153	154
Median (95% Confidence Interval); Unit of Measure: months
	5.06; (3.778 to 7.885)	4.30; (2.891 to 5.125)

12. Secondary Outcome

Title	Number of Participants With Minimal Residual Disease (MRD)
Description	MRD was assessed by next-generation sequencing in bone marrow samples from participants who achieved CR, to determine the depth of response at the molecular level. IMWG criteria for CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. MRD was classified as positive or negative at the minimum sensitivity of 1 in 10^5 nucleated cells. MRD negativity was defined as the absence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening. MRD positivity was defined as the presence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening.
Time Frame	Up to 76.7 weeks

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population who were evaluable for MRD.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	2	14
Measure Type: Count of Participants; Unit of Measure: Participants
MRD negative:1 in 10^4	0 0.0%	10 71.4%
MRD negative:1 in 10^5	0 0.0%	8 57.1%
MRD negative:1 in 10^6	0 0.0%	2 14.3%
MRD positive:1 in 10^4	2 100.0%	4 28.6%
MRD positive:1 in 10^5	2 100.0%	6 42.9%
MRD positive:1 in 10^6	2 100.0%	9 64.3%

13. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.
Time Frame	From randomization up to 30 days after last dose of study drug (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population which included all participants from the ITT population who received at least one dose or a part of a dose of the study treatments.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 241.6 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 245.6 weeks).
Overall Number of Participants Analyzed	149	152
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE	146 98.0%	151 99.3%
Any treatment emergent SAE	91 61.1%	112 73.7%
Any TEAE leading to treatment discontinuation	22 14.8%	19 12.5%

14. Secondary Outcome

Title	Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI)
Description	CEOI was defined as the plasma concentration at end of infusion.
Time Frame	End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population which included participants who received at least 1 dose of Isatuximab, with data for at least 1 PK parameter available. Here, 'Number analyzed' = participants with available data for each specified category. Data for this outcome measure (OM) was not planned to be collected and analyzed for Pd arm.

Arm/Group Title		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		149
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: microgram per milliliter (mcg/mL)
End of infusion: C1D1	Number Analyzed	141 participants
		163.05; (34.528%)
End of infusion: C1D15	Number Analyzed	120 participants
		269.20; (32.622%)
End of infusion: C2D1	Number Analyzed	134 participants
		299.85; (35.921%)
End of infusion: C4D1	Number Analyzed	117 participants
		279.31; (47.555%)

15. Secondary Outcome

Title	Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI)
Description	Accumulation Ratio was defined as the ratio of CEOI of Cycle 2 Day 1 versus Cycle 1 Day 1 and Cycle 4 Day 1 versus Cycle 1 Day 1, where CEOI was the plasma concentration at the end of infusion.
Time Frame	End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Here, 'Number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for Pd arm.

Arm/Group Title		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		149
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ratio
C2D1 versus C1D1	Number Analyzed	130 participants
		1.860; (170.9185%)
C4D1 versus C1D1	Number Analyzed	112 participants
		1.777; (224.2542%)

16. Secondary Outcome

Title	Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour)
Description	CEOI+1 hour was defined as the plasma concentration of isatuximab at 1 hour after end of infusion.
Time Frame	Cycle 1:1 hour after End of Infusion on Day 1; Cycle 4:1 hour after End of Infusion on Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Here, 'Number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for Pd arm.

Arm/Group Title		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		149
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
C1D1	Number Analyzed	140 participants
		171.55; (38.299%)
C4D1	Number Analyzed	114 participants
		294.96; (57.331%)

17. Secondary Outcome

Title	PK Parameter: Plasma Concentration of Isatuximab at Ctrough
Description	Trough Concentration (Ctrough) is the concentration prior to study drug administration.
Time Frame	Pre-infusion on C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1; End of treatment (EOT [30 days after last drug administration])

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Here, 'Number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for Pd arm.

Arm/Group Title		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		149
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: mcg/mL
C1D1	Number Analyzed	144 participants
		0.00; (1194.973%)
C1D8	Number Analyzed	135 participants
		31.49; (53.602%)
C1D15	Number Analyzed	126 participants
		57.89; (54.764%)
C1D22	Number Analyzed	126 participants
		84.82; (57.666%)
C2D1	Number Analyzed	138 participants
		89.09; (60.155%)
C2D15	Number Analyzed	121 participants
		89.35; (61.167%)
C3D1	Number Analyzed	131 participants
		64.15; (76.469%)
C3D15	Number Analyzed	109 participants
		91.73; (78.406%)
C4D1	Number Analyzed	118 participants
		86.05; (70.062%)
C4D15	Number Analyzed	108 participants
		105.42; (68.035%)
C5D1	Number Analyzed	108 participants
		106.08; (65.275%)
C6D1	Number Analyzed	107 participants
		111.33; (64.985%)
C7D1	Number Analyzed	96 participants
		134.14; (60.017%)
C8D1	Number Analyzed	86 participants
		146.15; (55.946%)
C9D1	Number Analyzed	82 participants
		162.84; (65.193%)
C10D1	Number Analyzed	73 participants
		145.86; (60.719%)
C11D1	Number Analyzed	71 participants
		169.39; (56.078%)
C12D1	Number Analyzed	63 participants
		182.32; (56.814%)
C13D1	Number Analyzed	49 participants
		215.85; (54.667%)
C14D1	Number Analyzed	35 participants
		214.88; (55.172%)
C15D1	Number Analyzed	24 participants
		253.61; (58.885%)
C16D1	Number Analyzed	19 participants
		206.60; (50.965%)
C17D1	Number Analyzed	13 participants
		242.79; (45.364%)
C18D1	Number Analyzed	8 participants
		216.70; (58.273%)
C19D1	Number Analyzed	5 participants
		240.36; (42.099%)
C20D1	Number Analyzed	1 participants
		164.07
EOT	Number Analyzed	60 participants
		9.51; (136.883%)

18. Secondary Outcome

Title	PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough)
Description	Accumulation Ratio was defined as the ratio of Ctrough of Cycle 2 Day 1 versus Cycle 1 Day 8 and Cycle 4 Day 1 versus Cycle 1 Day 8, where Ctrough is the concentration prior to study drug administration.
Time Frame	Pre-infusion on Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 4 Day 1

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Here, 'Number analyzed' = participants with available data for each specified category. Data for this OM was not planned to be collected and analyzed for Pd arm.

Arm/Group Title		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		149
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: ratio
C2D1 versus C1D8	Number Analyzed	125 participants
		2.689; (734.5547%)
C4D1 versus C1D8	Number Analyzed	108 participants
		2.620; (645.4171%)

19. Secondary Outcome

Title	Number of Participants With Anti-drug Antibodies (ADA)
Description	ADA were categorized as: pre-existing, treatment induced and treatment boosted response. Pre-existing ADA was defined as ADA that were present in samples drawn during the pretreatment period (i.e., before the first isatuximab administration). Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without preexisting ADA, including participants without pretreatment samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment and post-treatment.
Time Frame	From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ADA evaluable population which included participants who received at least one dose of study drug from the IPd arm with at least one ADA assessment during the ADA on-study observation period with a reportable result. Data for this OM was not planned to be collected and analyzed for Pd arm.

Arm/Group Title	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed	151
Measure Type: Count of Participants; Unit of Measure: Participants
Pre-existing ADA	0 0.0%
Treatment induced ADA	0 0.0%
Treatment boosted ADA	0 0.0%

20. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score
Description	EORTC-Quality of Life Questionnaire (QLQ)-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. EORTC QLQ-C30 included GHS/ QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.
Time Frame	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population evaluable for global health status. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title		Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		134	139
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	134 participants	137 participants
		61.19 (20.64)	60.10 (20.02)
Day 1: Cycle 3	Number Analyzed	109 participants	123 participants
		-1.45 (21.03)	-1.22 (22.42)
Day 1: Cycle 6	Number Analyzed	69 participants	102 participants
		-0.12 (22.26)	-0.16 (18.28)
Day 1: Cycle 9	Number Analyzed	55 participants	82 participants
		1.06 (19.97)	0.41 (20.99)
Day 1: Cycle 17	Number Analyzed	10 participants	13 participants
		-9.17 (24.36)	-1.92 (19.29)

21. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score
Description	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Disease symptoms domain is one of the four domain scores. Disease symptoms domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL
Time Frame	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population evaluable for disease symptoms. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title		Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		130	137
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	130 participants	135 participants
		24.91 (20.67)	24.12 (20.54)
Day 1: Cycle 3	Number Analyzed	107 participants	121 participants
		-3.79 (16.09)	-2.07 (17.51)
Day 1: Cycle 6	Number Analyzed	68 participants	101 participants
		-4.08 (17.95)	-3.30 (16.01)
Day 1: Cycle 9	Number Analyzed	55 participants	81 participants
		-2.83 (15.04)	-4.66 (13.73)
Day 1: Cycle 17	Number Analyzed	10 participants	13 participants
		-3.33 (15.54)	0.00 (21.40)

22. Secondary Outcome

Title	Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score
Description	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Side effects of treatment domain is one of the four domain scores. Side effects of treatment domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale, where higher scores = more side effects and lower HRQL and lower scores = less side effects and better HRQL.
Time Frame	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population evaluable for side effects of treatment. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title		Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		130	137
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	130 participants	135 participants
		17.49 (15.25)	15.60 (11.63)
Day 1: Cycle 3	Number Analyzed	107 participants	121 participants
		1.69 (11.54)	2.61 (13.39)
Day 1: Cycle 6	Number Analyzed	68 participants	101 participants
		-0.13 (15.10)	2.11 (11.78)
Day 1: Cycle 9	Number Analyzed	55 participants	81 participants
		1.43 (14.66)	3.14 (11.88)
Day 1: Cycle 17	Number Analyzed	10 participants	13 participants
		-2.93 (15.94)	3.02 (15.72)

23. Secondary Outcome

Title	Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value
Description	The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health and wellbeing. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale (for the 5L version). The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state.
Time Frame	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population evaluable for health state utility index. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title		Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		134	140
Mean (Standard Deviation); Unit of Measure: score on a scale
Baseline	Number Analyzed	134 participants	138 participants
		0.70 (0.24)	0.71 (0.21)
Day 1: Cycle 3	Number Analyzed	109 participants	125 participants
		-0.01 (0.22)	-0.01 (0.22)
Day 1: Cycle 6	Number Analyzed	69 participants	101 participants
		0.02 (0.22)	-0.00 (0.20)
Day 1: Cycle 9	Number Analyzed	55 participants	82 participants
		-0.03 (0.27)	-0.01 (0.15)
Day 1: Cycle 17	Number Analyzed	10 participants	13 participants
		-0.02 (0.19)	-0.01 (0.23)

24. Secondary Outcome

Title	Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions, 5 Levels (EQ-5D-5L) Score: Visual Analogic Scale (VAS)
Description	EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.
Time Frame	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population evaluable for visual analogue scale. Here, 'Number analyzed' = participants with available data for each specified category.

Arm/Group Title		Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description:		Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Number of Participants Analyzed		134	140
Mean (Standard Deviation); Unit of Measure: centimeter
Baseline	Number Analyzed	134 participants	138 participants
		65.38 (19.31)	66.62 (19.32)
Day 1: Cycle 3	Number Analyzed	109 participants	125 participants
		0.26 (17.37)	0.92 (19.41)
Day 1: Cycle 6	Number Analyzed	69 participants	101 participants
		2.49 (18.83)	1.19 (17.70)
Day 1: Cycle 9	Number Analyzed	55 participants	82 participants
		4.42 (19.78)	1.96 (16.60)
Day 1: Cycle 17	Number Analyzed	10 participants	13 participants
		-1.70 (12.39)	-3.00 (12.58)

Adverse Events

Time Frame	AE data was collected from the time of first dose of study drug administration up to 30 days following the last administration of study treatment (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)
Adverse Event Reporting Description	Reported AEs and deaths are TEAEs that developed, worsened, or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). All-Cause Mortality was assessed for all randomized participants, Serious and Other Adverse Events were collected for safety population only.
Arm/Group Title	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 241.6 weeks).		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 245.6 weeks).
All-Cause Mortality
	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	115/153 (75.16%)		109/154 (70.78%)
Serious Adverse Events
	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	91/149 (61.07%)		112/152 (73.68%)
Blood and lymphatic system disorders
Anaemia † 1	1/149 (0.67%)	1	3/152 (1.97%)	4
Febrile Neutropenia † 1	5/149 (3.36%)	5	10/152 (6.58%)	12
Hyperviscosity Syndrome † 1	2/149 (1.34%)	2	0/152 (0.00%)	0
Neutropenia † 1	2/149 (1.34%)	2	5/152 (3.29%)	5
Pancytopenia † 1	1/149 (0.67%)	1	1/152 (0.66%)	1
Splenic Infarction † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Thrombocytopenia † 1	1/149 (0.67%)	1	3/152 (1.97%)	3
Cardiac disorders
Acute Coronary Syndrome † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Angina Pectoris † 1	2/149 (1.34%)	2	0/152 (0.00%)	0
Angina Unstable † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Arrhythmia Supraventricular † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Arteriosclerosis Coronary Artery † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Atrial Fibrillation † 1	1/149 (0.67%)	1	3/152 (1.97%)	4
Cardiac Failure † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Cardiac Failure Chronic † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Diastolic Dysfunction † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Myocardial Infarction † 1	1/149 (0.67%)	1	3/152 (1.97%)	3
Eye disorders
Cataract † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Retinal Detachment † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Vision Blurred † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Gastrointestinal disorders
Abdominal Pain Upper † 1	0/149 (0.00%)	0	1/152 (0.66%)	2
Colitis Ischaemic † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Diarrhoea † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Diverticular Perforation † 1	0/149 (0.00%)	0	2/152 (1.32%)	3
Gastrointestinal Haemorrhage † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Intestinal Obstruction † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Large Intestine Perforation † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Oesophagitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pancreatitis Acute † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
General disorders
Asthenia † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Death † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Disease Progression † 1	8/149 (5.37%)	8	9/152 (5.92%)	9
General Physical Health Deterioration † 1	3/149 (2.01%)	3	1/152 (0.66%)	1
Influenza Like Illness † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Multiple Organ Dysfunction Syndrome † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Oedema Peripheral † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Peripheral Swelling † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pyrexia † 1	2/149 (1.34%)	2	5/152 (3.29%)	5
Sudden Death † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Hepatobiliary disorders
Bile Duct Stone † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Cholecystitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Hepatic Failure † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Infections and infestations
Acarodermatitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Atypical Pneumonia † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Bronchiolitis † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Bronchitis † 1	1/149 (0.67%)	1	7/152 (4.61%)	8
Covid-19 † 1	2/149 (1.34%)	2	0/152 (0.00%)	0
Covid-19 Pneumonia † 1	2/149 (1.34%)	2	1/152 (0.66%)	1
Candida Pneumonia † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Cellulitis Staphylococcal † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Coronavirus Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Cytomegalovirus Gastrointestinal Infection † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Device Related Sepsis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Diverticulitis † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Ear, Nose And Throat Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Escherichia Sepsis † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Gastroenteritis † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Gastroenteritis Enteroviral † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Haemophilus Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Herpes Zoster Disseminated † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Infection † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Influenza † 1	2/149 (1.34%)	2	4/152 (2.63%)	4
Laryngitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Lower Respiratory Tract Infection † 1	3/149 (2.01%)	3	7/152 (4.61%)	8
Lymphangitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Medical Device Site Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Meningitis Cryptococcal † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Meningitis Listeria † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Neurological Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Orchitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Periorbital Cellulitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pneumocystis Jirovecii Pneumonia † 1	5/149 (3.36%)	5	4/152 (2.63%)	4
Pneumonia † 1	31/149 (20.81%)	33	35/152 (23.03%)	51
Pneumonia Bacterial † 1	1/149 (0.67%)	1	5/152 (3.29%)	6
Pneumonia Fungal † 1	1/149 (0.67%)	1	1/152 (0.66%)	1
Pneumonia Haemophilus † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Pneumonia Influenzal † 1	2/149 (1.34%)	2	2/152 (1.32%)	2
Pneumonia Pneumococcal † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Pneumonia Streptococcal † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Pneumonia Viral † 1	0/149 (0.00%)	0	3/152 (1.97%)	3
Postoperative Wound Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pseudomonal Bacteraemia † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pseudomonas Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pyelonephritis † 1	1/149 (0.67%)	1	1/152 (0.66%)	1
Pyelonephritis Acute † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Pyoderma † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Respiratory Tract Infection † 1	2/149 (1.34%)	2	2/152 (1.32%)	2
Sepsis † 1	2/149 (1.34%)	2	4/152 (2.63%)	4
Septic Shock † 1	4/149 (2.68%)	4	1/152 (0.66%)	1
Sinusitis † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Skin Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Soft Tissue Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Staphylococcal Bacteraemia † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Systemic Candida † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Upper Respiratory Tract Infection † 1	5/149 (3.36%)	5	1/152 (0.66%)	1
Urinary Tract Infection † 1	2/149 (1.34%)	2	7/152 (4.61%)	8
Varicella † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Viral Upper Respiratory Tract Infection † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Injury, poisoning and procedural complications
Accidental Overdose † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Fall † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Femoral Neck Fracture † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Femur Fracture † 1	1/149 (0.67%)	1	3/152 (1.97%)	3
Head Injury † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Infusion Related Reaction † 1	1/149 (0.67%)	1	6/152 (3.95%)	6
Spinal Compression Fracture † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Tibia Fracture † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Wound Complication † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Investigations
Alanine Aminotransferase Increased † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Hepatic Enzyme Increased † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Metabolism and nutrition disorders
Decreased Appetite † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Dehydration † 1	1/149 (0.67%)	1	1/152 (0.66%)	1
Hypercalcaemia † 1	3/149 (2.01%)	4	2/152 (1.32%)	2
Hyperglycaemia † 1	0/149 (0.00%)	0	3/152 (1.97%)	4
Hypocalcaemia † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Hyponatraemia † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Hypophosphataemia † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Malnutrition † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Metabolic Disorder † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Tumour Lysis Syndrome † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	2/149 (1.34%)	2	3/152 (1.97%)	3
Back Pain † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Bone Pain † 1	0/149 (0.00%)	0	3/152 (1.97%)	3
Muscular Weakness † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Osteonecrosis Of Jaw † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Osteoporotic Fracture † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pathological Fracture † 1	4/149 (2.68%)	4	7/152 (4.61%)	7
Soft Tissue Necrosis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Basal Cell Carcinoma † 1	1/149 (0.67%)	1	1/152 (0.66%)	1
Lip Neoplasm Malignant Stage Unspecified † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Lip Squamous Cell Carcinoma † 1	0/149 (0.00%)	0	1/152 (0.66%)	2
Metastatic Malignant Melanoma † 1	0/149 (0.00%)	0	1/152 (0.66%)	2
Myelodysplastic Syndrome † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Squamous Cell Carcinoma Of Skin † 1	0/149 (0.00%)	0	4/152 (2.63%)	5
Tumour Associated Fever † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Nervous system disorders
Ataxia † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Basal Ganglia Infarction † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Cauda Equina Syndrome † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Cerebellar Infarction † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Cerebral Haemorrhage † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Depressed Level Of Consciousness † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Haemorrhage Intracranial † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Intracranial Aneurysm † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Ischaemic Stroke † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Presyncope † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Spinal Subdural Haematoma † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Syncope † 1	1/149 (0.67%)	1	4/152 (2.63%)	4
Transient Ischaemic Attack † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Vith Nerve Paresis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Vocal Cord Paralysis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Psychiatric disorders
Acute Psychosis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Confusional State † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Delirium † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Renal and urinary disorders
Acute Kidney Injury † 1	6/149 (4.03%)	8	6/152 (3.95%)	6
Hydronephrosis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Renal Aneurysm † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Renal Failure † 1	3/149 (2.01%)	4	1/152 (0.66%)	1
Renal Impairment † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Reproductive system and breast disorders
Pelvic Pain † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Prostatitis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Bronchopneumopathy † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Bronchospasm † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Chronic Obstructive Pulmonary Disease † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Cough † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Dyspnoea † 1	2/149 (1.34%)	2	4/152 (2.63%)	4
Haemothorax † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Hiccups † 1	0/149 (0.00%)	0	1/152 (0.66%)	2
Hypoxia † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pleural Effusion † 1	1/149 (0.67%)	1	2/152 (1.32%)	2
Pulmonary Embolism † 1	2/149 (1.34%)	2	3/152 (1.97%)	3
Pulmonary Hypertension † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Pulmonary Oedema † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Respiratory Failure † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Skin and subcutaneous tissue disorders
Decubitus Ulcer † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Diabetic Ulcer † 1	1/149 (0.67%)	3	0/152 (0.00%)	0
Vascular disorders
Arteriosclerosis † 1	0/149 (0.00%)	0	1/152 (0.66%)	1
Deep Vein Thrombosis † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Hypertension † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
Hypotension † 1	0/149 (0.00%)	0	2/152 (1.32%)	2
Orthostatic Hypotension † 1	1/149 (0.67%)	1	0/152 (0.00%)	0
1 Term from vocabulary, MedDRA 24.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	139/149 (93.29%)		145/152 (95.39%)
Blood and lymphatic system disorders
Febrile Neutropenia † 1	0/149 (0.00%)	0	8/152 (5.26%)	10
Neutropenia † 1	52/149 (34.90%)	96	77/152 (50.66%)	182
Thrombocytopenia † 1	17/149 (11.41%)	19	19/152 (12.50%)	27
Cardiac disorders
Atrial Fibrillation † 1	2/149 (1.34%)	2	8/152 (5.26%)	11
Eye disorders
Cataract † 1	11/149 (7.38%)	11	13/152 (8.55%)	14
Gastrointestinal disorders
Abdominal Pain † 1	6/149 (4.03%)	7	8/152 (5.26%)	8
Constipation † 1	30/149 (20.13%)	35	27/152 (17.76%)	37
Diarrhoea † 1	32/149 (21.48%)	44	48/152 (31.58%)	85
Nausea † 1	14/149 (9.40%)	14	24/152 (15.79%)	27
Stomatitis † 1	4/149 (2.68%)	4	10/152 (6.58%)	14
Vomiting † 1	6/149 (4.03%)	6	20/152 (13.16%)	22
General disorders
Asthenia † 1	29/149 (19.46%)	36	23/152 (15.13%)	37
Fatigue † 1	32/149 (21.48%)	34	30/152 (19.74%)	43
Oedema Peripheral † 1	18/149 (12.08%)	22	30/152 (19.74%)	38
Pyrexia † 1	19/149 (12.75%)	21	22/152 (14.47%)	27
Infections and infestations
Bronchitis † 1	16/149 (10.74%)	29	37/152 (24.34%)	65
Influenza † 1	6/149 (4.03%)	7	8/152 (5.26%)	9
Nasopharyngitis † 1	10/149 (6.71%)	13	23/152 (15.13%)	44
Oral Herpes † 1	3/149 (2.01%)	3	10/152 (6.58%)	19
Pneumonia † 1	10/149 (6.71%)	10	18/152 (11.84%)	29
Upper Respiratory Tract Infection † 1	28/149 (18.79%)	51	53/152 (34.87%)	119
Urinary Tract Infection † 1	13/149 (8.72%)	15	15/152 (9.87%)	21
Injury, poisoning and procedural complications
Fall † 1	9/149 (6.04%)	11	11/152 (7.24%)	15
Infusion Related Reaction † 1	1/149 (0.67%)	1	52/152 (34.21%)	56
Investigations
Weight Decreased † 1	2/149 (1.34%)	3	10/152 (6.58%)	10
Metabolism and nutrition disorders
Decreased Appetite † 1	8/149 (5.37%)	9	17/152 (11.18%)	23
Musculoskeletal and connective tissue disorders
Arthralgia † 1	18/149 (12.08%)	18	19/152 (12.50%)	22
Back Pain † 1	24/149 (16.11%)	25	29/152 (19.08%)	32
Bone Pain † 1	13/149 (8.72%)	14	11/152 (7.24%)	13
Muscle Spasms † 1	16/149 (10.74%)	19	17/152 (11.18%)	18
Muscular Weakness † 1	8/149 (5.37%)	8	13/152 (8.55%)	14
Musculoskeletal Chest Pain † 1	7/149 (4.70%)	7	15/152 (9.87%)	16
Myalgia † 1	5/149 (3.36%)	5	12/152 (7.89%)	14
Pain In Extremity † 1	5/149 (3.36%)	6	12/152 (7.89%)	12
Nervous system disorders
Dizziness † 1	5/149 (3.36%)	5	10/152 (6.58%)	11
Headache † 1	9/149 (6.04%)	9	16/152 (10.53%)	18
Peripheral Sensory Neuropathy † 1	11/149 (7.38%)	11	18/152 (11.84%)	20
Tremor † 1	7/149 (4.70%)	7	13/152 (8.55%)	14
Psychiatric disorders
Insomnia † 1	14/149 (9.40%)	17	15/152 (9.87%)	17
Respiratory, thoracic and mediastinal disorders
Cough † 1	11/149 (7.38%)	15	14/152 (9.21%)	22
Dyspnoea † 1	13/149 (8.72%)	14	23/152 (15.13%)	33
Oropharyngeal Pain † 1	4/149 (2.68%)	4	12/152 (7.89%)	15
Productive Cough † 1	3/149 (2.01%)	3	8/152 (5.26%)	12
Skin and subcutaneous tissue disorders
Pruritus † 1	11/149 (7.38%)	12	9/152 (5.92%)	9
Rash † 1	8/149 (5.37%)	8	11/152 (7.24%)	12
Vascular disorders
Hypertension † 1	7/149 (4.70%)	9	11/152 (7.24%)	17
1 Term from vocabulary, MedDRA 24.1; † 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 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 supports publication of clinical trial results but may request that investigators temporarily delay or alter publications in order to protect proprietary information. The Sponsor may also require that the results of multicenter studies be published only in their entirety and not as individual site data.

Results Point of Contact

• Name/Title: Trial Transparency Team
• Organization: Sanofi aventis recherche & développement
• Phone: 800-633-1610 ext 6#
• EMail: Contact-US@sanofi.com

Publications:

Attal M, Richardson PG, Rajkumar SV, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Mace S, Corzo KP, Campana F, Le-Guennec S, Dubin F, Anderson KC; ICARIA-MM study group. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): a randomised, multicentre, open-label, phase 3 study. Lancet. 2019 Dec 7;394(10214):2096-2107. doi: 10.1016/S0140-6736(19)32556-5. Epub 2019 Nov 14. Erratum In: Lancet. 2019 Dec 7;394(10214):2072.

Richardson PG, Perrot A, San-Miguel J, Beksac M, Spicka I, Leleu X, Schjesvold F, Moreau P, Dimopoulos MA, Huang JS, Minarik J, Cavo M, Prince HM, Malinge L, Dubin F, van de Velde H, Anderson KC. Isatuximab plus pomalidomide and low-dose dexamethasone versus pomalidomide and low-dose dexamethasone in patients with relapsed and refractory multiple myeloma (ICARIA-MM): follow-up analysis of a randomised, phase 3 study. Lancet Oncol. 2022 Mar;23(3):416-427. doi: 10.1016/S1470-2045(22)00019-5. Epub 2022 Feb 10. Erratum In: Lancet Oncol. 2022 Apr;23(4):e161. Lancet Oncol. 2022 Sep;23(9):e404.

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

Sunami K, Ikeda T, Huang SY, Wang MC, Koh Y, Min CK, Yeh SP, Matsumoto M, Uchiyama M, Iyama S, Shimazaki C, Lee JH, Kim K, Kaneko H, Kim JS, Lin TL, Campana F, Tada K, Iida S, Suzuki K; ICARIA-MM study group. Isatuximab-Pomalidomide-Dexamethasone Versus Pomalidomide-Dexamethasone in East Asian Patients With Relapsed/Refractory Multiple Myeloma: ICARIA-MM Subgroup Analysis. Clin Lymphoma Myeloma Leuk. 2022 Aug;22(8):e751-e761. doi: 10.1016/j.clml.2022.04.005. Epub 2022 Apr 8.

Wilmoth J, Colson K, Dubin F, Kellam C. Isatuximab: Nursing Considerations for Use in the Treatment of Multiple Myeloma. Clin J Oncol Nurs. 2021 Dec 1;25(6):706-712. doi: 10.1188/21.CJON.706-712.

Bringhen S, Pour L, Vorobyev V, Vural F, Warzocha K, Benboubker L, Koh Y, Maisnar V, Karlin L, Pavic M, Campana F, Le Guennec S, Menas F, van de Velde H, Richardson PG. Isatuximab plus pomalidomide and dexamethasone in patients with relapsed/refractory multiple myeloma according to prior lines of treatment and refractory status: ICARIA-MM subgroup analysis. Leuk Res. 2021 May;104:106576. doi: 10.1016/j.leukres.2021.106576. Epub 2021 Mar 29.

Schjesvold FH, Richardson PG, Facon T, Alegre A, Spencer A, Jurczyszyn A, Sunami K, Frenzel L, Min CK, Guillonneau S, Lin PL, Le-Guennec S, Campana F, van de Velde H, Bensfia S, Bringhen S. Isatuximab plus pomalidomide and dexamethasone in elderly patients with relapsed/refractory multiple myeloma: ICARIA-MM subgroup analysis. Haematologica. 2021 Apr 1;106(4):1182-1187. doi: 10.3324/haematol.2020.253450. No abstract available.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02990338
• Other Study ID Numbers: EFC14335; U1111-1180-6262 ( Registry Identifier: ICTRP ); 2016-003097-41 ( EudraCT Number )
• First Submitted: December 4, 2016
• First Posted: December 13, 2016
• Results First Submitted: November 19, 2019
• Results First Posted: December 6, 2019
• Last Update Posted: November 18, 2023