Multinational Clinical Study Comparing Isatuximab, Carfilzomib And Dexamethasone To Carfilzomib And Dexamethasone In Relapse And/Or Refractory Multiple Myeloma Patients (IKEMA)

• ClinicalTrials.gov Identifier: NCT03275285
• Recruitment Status: Active, not recruiting
• First Posted: September 7, 2017
• Results First Posted: February 13, 2023
• Last Update Posted: February 20, 2024
• Sponsor: Sanofi
• Information provided by (Responsible Party): Sanofi

• Study Type: Interventional
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment
• Condition: Plasma Cell Myeloma
• Interventions: Drug: isatuximab SAR650984; Drug: carfilzomib; Drug: dexamethasone
• Enrollment: 302

Participant Flow

Recruitment Details

The study was conducted at 69 active centers in 16 countries. A total of 341 participants were screened between 25 October 2017 and 21 March 2019, of which 39 participants were screen failure due to not meeting eligibility criteria. Randomization was stratified by number of prior lines (1 versus >1) & revised international staging system (R-ISS) I or II versus III versus not classified. Total of 302 participants were enrolled & randomized in the study.

Pre-assignment Details

Study is ongoing, first result analysis reported was for a data cut-off date of 7 Feb 2020 for efficacy outcomes, 14 Jan 2022 for CR, MRD and PFS2. PFS data was reported at both cut-off dates: 7 Feb 2020 & 14 Jan 2022. Primary analysis of PFS refers to planned interim analysis conducted at 103 events (death/PD) with cut-off date 7 Feb 2020 & planned final analysis of PFS conducted at 159 events with cut-off date 14 Jan 2022. Data cut-off for results analysis of overal survival was 7 Feb 2023.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description	Participants received carfilzomib 20 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 milligrams (mg), orally (PO) or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 265 weeks).	Participants received isatuximab 10 milligrams per kilogram (mg/kg), IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 268 weeks).
Period Title: Overall Study
Started	123	179
Treated	122	177
Completed	78	110
Not Completed	45	69
Reason Not Completed
Ongoing	45	69

Baseline Characteristics

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)	Total
Arm/Group Description		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 265 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 268 weeks).	Total of all reporting groups
Overall Number of Baseline Participants		123	179	302
Baseline Analysis Population Description		Analysis was performed on randomized population.
Age, Continuous; Mean (Standard Deviation); Unit of measure: Years
	Number Analyzed	123 participants	179 participants	302 participants
		62.9 (10.0)	63.3 (9.8)	63.1 (9.9)
Sex: Female, Male; Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	123 participants	179 participants	302 participants
	Female	55 44.7%	78 43.6%	133 44.0%
	Male	68 55.3%	101 56.4%	169 56.0%
Race (NIH/OMB); Measure Type: Count of Participants; Unit of measure: Participants
	Number Analyzed	123 participants	179 participants	302 participants
	American Indian or Alaska Native	0 0.0%	0 0.0%	0 0.0%
	Asian	24 19.5%	26 14.5%	50 16.6%
	Native Hawaiian or Other Pacific Islander	0 0.0%	0 0.0%	0 0.0%
	Black or African American	4 3.3%	5 2.8%	9 3.0%
	White	83 67.5%	131 73.2%	214 70.9%
	More than one race	0 0.0%	3 1.7%	3 1.0%
	Unknown or Not Reported	12 9.8%	14 7.8%	26 8.6%

Outcome Measures

1. Primary Outcome

Title	Progression Free Survival (PFS) As Determined by Independent Response Committee (IRC): Primary Analysis
Description	Time (in months) from randomization to date of 1st documentation of progressive disease (PD)/date of death from any cause, whichever comes 1st. If PD & death are not observed before cut-off date/date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment not showing PD performed prior to initiation of further anti-myeloma treatment/cut-off date, whichever comes 1st. PD(IMWG criteria):any 1 of following:Increase(inc) of >=25% in serum M-component from nadir; serum M component inc >=1 g/dL in 2 consecutive assessment, if starting M component >=5 g/dL; and/or inc of >=25% in urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc >=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion if >1 lesion/ >=50% increase in longest diameter of previous soft tissue extramedullary disease lesion >1 cm in short axis. Estimated by Kaplan-Meier method.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on Intent to Treat (ITT) population that included all participants who gave their informed consent and for whom there was a confirmation of successful allocation of a randomization number by the interactive response technology (IRT).

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	19.15 [1]; (15.770 to NA)	NA [2]; (NA to NA)

[1]

Upper limit of the confidence interval could not be reached due to less number of participants with the events.

[2]

Median value and the upper and lower limit of the confidence interval could not be calculated because of less than 50% of the participants had PFS events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	Statistical analysis for comparison of PFS between the Kd and IKd arms based on primary analysis.
	Type of Statistical Test	Superiority
	Comments	For PFS, the nominal significance levels at primary analysis was determined using alpha-spending function in order to control overall 1-sided type 1 error at 2.5%. The 1-sided nominal significance level to declare overwhelming efficacy at primary analysis (103 PFS events) was 0.005. Because the median PFS was not reached at the primary analysis, it was described at the final analysis.
Statistical Test of Hypothesis	P-Value	0.0007
	Comments	One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.005.
	Method	Stratified Log-Rank test
	Comments	Stratified on number of prior lines of therapy (1 vs >1) & revised international staging system stage (I/II vs III vs not classified) as per IRT.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.531
	Confidence Interval	(2-Sided) 99%; 0.318 to 0.889
	Estimation Comments	Hazard Ratio was stratified on number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

2. Primary Outcome

Title	Progression Free Survival as Determined by Independent Response Committee: [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Primary Analysis
Description	Time (in months) from randomization to date of 1st PD documentation/death date, whichever is 1st. If PD & death not observed before cut-off date/date of further anti-myeloma treatment initiation, PFS censored at date of last valid disease assessment not showing PD performed prior to initiation of further anti-myeloma treatment/cut-off date, whichever was 1st. Progression/deaths occurring >8 weeks after last disease assessment censored at earliest date of last disease assessment without evidence of progression before initiation of new anti-myeloma treatment & cut-off date. PD (IMWG criteria): meeting any 1: Inc >=25% in Serum M-component from nadir; serum M component inc >=1 g/dL in 2 consecutive assessment, if starting M component >=5 g/dL; and/or inc >=25% in Urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc >=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion >1 cm short axis.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	20.27 [1]; (15.770 to NA)	NA [2]; (NA to NA)

[1]

Upper limit of the confidence interval could not be reached due to less number of participants with the events.

[2]

Median value and the upper and lower limit of the confidence interval could not be calculated because of less than 50% of the participants had PFS events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	Statistical analysis for comparison of PFS between the Kd and IKd arm based on primary analysis.
	Type of Statistical Test	Superiority
	Comments	The 1-sided nominal significance level to declare overwhelming efficacy at primary analysis was 0.004. Because the median PFS was not reached at the primary analysis, it was described at the final analysis.
Statistical Test of Hypothesis	P-Value	0.0016
	Comments	One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.004.
	Method	Stratified Log-Rank test
	Comments	Stratified on number of prior lines of therapy (1 vs >1) & revised international staging system stage (I/II vs III vs not classified) as per IRT.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.548
	Confidence Interval	(2-Sided) 99.2%; 0.317 to 0.948
	Estimation Comments	Hazard Ratio was stratified on number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

3. Primary Outcome

Title	Progression Free Survival as Determined by Independent Response Committee: Final Analysis
Description	PFS: time (in months) from randomization to date of first documentation of PD or date of death from any cause, whichever comes first. If PD and death are not observed before analysis cut-off date or date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment or analysis cut-off date, whichever comes first. PD as per IMWG criteria: any 1 of following: Inc of >=25% in Serum M-component from nadir; serum M component increase >=1 g/dL in 2 consecutive assessment, if starting M component was >=5 g/dL; and/or inc of >=25% in Urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc >=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion if >1 lesion/ >=50% inc in longest diameter of previous soft tissue extramedullary disease lesion >1 cm in short axis. PFS estimated by Kaplan-Meier method.
Time Frame	From randomization until the final analysis data cut-off date of 14 January 2022 (the median duration of follow-up was 43.96 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 milligrams per meter square (mg/m^2), intravenous (IV) infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 milligrams (mg), orally (PO) or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 208 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 215 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	19.15; (15.770 to 25.035)	35.65; (25.758 to 43.959)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.576
	Confidence Interval	(2-Sided) 95.4%; 0.418 to 0.792
	Estimation Comments	Hazard Ratio was stratified on number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

4. Primary Outcome

Title	Progression Free Survival as Determined by Independent Response Committee [Event Censored if Occurred >8 Weeks From Last Disease Assessment]: Final Analysis
Description	Time (in months) from randomization to date of 1st documentation of PD/date of death from any cause, whichever comes 1st. If PD & death are not observed before cut-off date/date of initiation of further anti-myeloma treatment, PFS was censored at date of last valid disease assessment not showing PD/cut-off date, whichever comes 1st. Progressions/deaths occurring >8 weeks after last disease assessment were censored at earliest date of last valid disease assessment not showing PD before initiation of further anti-myeloma treatment & cut-off date. PD (per IMWG criteria): meeting any 1 criteria: Inc of >=25% in serum M-component from nadir; serum M component inc >=1 g/dL in 2 consecutive assessment, if starting M component was >=5 g/dL; and/or inc of >=25% in urine M-component from nadir and/or development of new bone lesion/soft tissue extramedullary disease/inc >=50% from nadir in sum of perpendicular diameters of existing soft tissue extramedullary disease lesion >1 cm in short axis.
Time Frame	From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the ITT population. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 208 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 215 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	20.76; (16.164 to 28.189)	41.66 [1]; (27.138 to NA)

[1]

Upper limit of the confidence interval could not be reached due to less number of participants with the events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.594
	Confidence Interval	(2-Sided) 95.4%; 0.424 to 0.832
	Estimation Comments	Hazard Ratio was stratified on number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

5. Secondary Outcome

Title	Percentage of Participants With Overall Response (OR) as Determined by Independent Response Committee: Primary Analysis
Description	OR: participants with sCR, CR, VGPR & partial response (PR) as best overall response assessed by IRC using IMWG response criteria (from start of treatment until disease progression, death, initiation of further anti-myeloma treatment/cutoff date, whichever occurs 1st). sCR: negative immunofixation on serum & urine, disappearance of soft tissue plasmacytoma, <5% plasma cells in bone marrow aspirate (BMA) + normal FLC ratio (0.26-1.65), absence of clonal cells in bone marrow biopsy. CR: negative immunofixation on serum & urine, disappearance of soft tissue plasmacytoma, <5% plasma cells in BMA. VGPR: serum & urine M-protein detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-protein + urine M-protein level <100mg/24h/,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR:>=50% reduction of serum M-protein & decrease in 24h urinary M-protein by >=90%/<200mg/24h, if present at baseline,>=50% decrease in SPD of soft tissue plasmacytoma.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Measure Type: Number; Unit of Measure: percentage of participants
	82.9	86.6

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	Statistical analysis for comparison of Overall Response between the Kd and IKd arms based on primary analysis.
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the Type I error rate from the primary efficacy endpoints sequentially through the secondary efficacy endpoints. No further testing would be performed unless the significance level had been reached on PFS and testing on subsequent endpoints were continued only if the null hypothesis for the previously tested endpoint was rejected.
Statistical Test of Hypothesis	P-Value	0.1930
	Comments	One-sided p-value based on Stratified Cochran-Mantel-Haenszel test. Threshold for statistical significance level at 0.025.
	Method	Cochran-Mantel-Haenszel
	Comments	One sided p-value was stratified based on randomization factors according to IRT.

6. Secondary Outcome

Title	Percentage of Participants With Very Good Partial Response (VGPR) or Better as Determined by Independent Response Committee: Primary Analysis
Description	VGPR or better: defined as participants with sCR, CR and VGPR as the best overall response (defined as best response from start of treatment until disease progression, death, initiation of further anti-myeloma treatment or cut-off date whichever occurs first) as per IRC. As per IMWG response criteria: sCR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in BMAs plus normal 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 BMAs. 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.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Measure Type: Number; Unit of Measure: percentage of participants
	56.1	72.6

7. Secondary Outcome

Title	Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Primary Analysis
Description	Percentage of participants with sCR, CR and VGPR for whom MRD assessed by sequencing was negative at any time after first dose of study treatment. MRD was assessed centrally by next-generation sequencing in bone marrow aspiration samples from participants who achieve VGPR or better, to determine depth of response at molecular level. VGPR or better: percentage of participants with sCR, CR and VGPR. sCR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in BMAs plus normal 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 BMAs. 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.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Measure Type: Number; Unit of Measure: percentage of participants
	13.0	29.6

8. Secondary Outcome

Title	Percentage of Participants With VGPR or Better With Minimal Residual Disease (MRD) Negativity: Final Analysis
Description	Percentage of participants with sCR, CR and VGPR for whom MRD assessed by sequencing was negative at any time after first dose of study treatment. MRD was assessed centrally by next-generation sequencing in BM aspiration samples from participants who achieve VGPR or better, to determine depth of response at molecular level. VGPR or better: percentage of participants with sCR, CR and VGPR. sCR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow aspirates plus normal FLC ratio, 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.
Time Frame	From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 208 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 215 weeks).
Overall Number of Participants Analyzed	123	179
Measure Type: Number; Unit of Measure: percentage of participants
	13.8	33.5

9. Secondary Outcome

Title	Percentage of Participants With Complete Response (CR) as Per Independent Response Committee: Final Analysis
Description	Complete response was defined as the participants with sCR and CR. IMWG response criteria for 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. Complete response at the time of the final analysis was assessed with hydrashift isatuximab immunofixation electrophoresis (IFE) assay, which separated immunoglobulin G (IgG) isatuximab from IgG M protein.
Time Frame	From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 208 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 215 weeks).
Overall Number of Participants Analyzed	123	179
Measure Type: Number; Unit of Measure: percentage of participants
	28.5	44.1

10. Secondary Outcome

Title	Percentage of Participants With Complete Response With MRD Negativity: Final Analysis
Description	MRD negativity was defined as the percentage of participants for whom MRD was negative by next-generation sequencing at any timepoint after first dose of study treatment. Threshold for negativity is 10^-5. MRD status in a participant was negative if at least one result of the assessment was negative in the participant otherwise MRD was considered as positive (MRD status reported as positive, missing or unevaluable). CR: participants with sCR and CR. IMWG response criteria for sCR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas, <5% plasma cells in bone marrow aspirates plus normal 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. Complete response at the time of the final analysis was assessed with Hydrashift isatuximab IFE assay, which separated IgG isatuximab from IgG M protein.
Time Frame	From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 208 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 215 weeks).
Overall Number of Participants Analyzed	123	179
Measure Type: Number; Unit of Measure: percentage of participants
	12.2	26.3

11. Secondary Outcome

Title	Overall Survival (OS)
Description	Overall survival, defined as the time from the date of randomization to death from any cause. The data reported is based on cut-off date of 7 Feb 2023.
Time Frame	From randomization until the final analysis data cut-off date of 7 Feb 2023 (the median duration of follow-up was 56.61 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 265 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 268 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	50.60 [1]; (38.932 to NA)	NA [2]; (52.172 to NA)

[1]

Upper limit of the confidence interval could not be reached due to less number of participants with the events.

[2]

Median value and the upper and lower limit of the confidence interval could not be calculated because of less than 50% of the participants had OS events.

12. Secondary Outcome

Title	Duration of Response (DOR): Primary Analysis
Description	DOR: time (in months) from date of 1st IRC determined response for participants achieving PR/better to date of 1st documented PD determined by IRC/death, whichever happens 1st. If disease progression/death before analysis cut-off date was not observed, DOR was censored at date of last valid disease assessment performed prior to initiation of further anti-myeloma treatment/data cut-off date, whichever was 1st. PD (IMWG criteria): inc of >=25% from lowest confirmed value in any 1 of following criteria: serum M-protein (absolute inc must be >=0.5 g/dL), serum M-protein inc >=1g/dL if lowest M component was >=5g/dL; urine M-component (absolute inc must be >=200mg/24 hour),appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >=50% inc in the longest diameter of previous lesion >1 cm in short axis. PR: >=50% reduction of serum M-protein & reduction in 24h urinary M-protein by >=90%/<200mg/24 h. Estimated by Kaplan Meier method.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on the subset of participants with PR or better (defined as responders) in ITT population.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	102	155
Median (95% Confidence Interval); Unit of Measure: months
	NA [1]; (14.752 to NA)	NA [2]; (NA to NA)

[1]

Median and upper limit of confidence interval could not be calculated because of less than 50% of the participants reaching PR or better with PFS events (PFS events includes progression and death without progression).

[2]

Median and the upper and lower limit of confidence interval could not be calculated because of less than 50% of the participants reaching PR or better with PFS events (PFS events includes progression and death without progression).

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.425
	Confidence Interval	(2-Sided) 95%; 0.269 to 0.672
	Estimation Comments	Stratification was done on the number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

13. Secondary Outcome

Title	Time to Progression (TTP): Primary Analysis
Description	TTP was defined as time in months from randomization to the date of first documentation of PD (as determined by the IRC). If progression was not observed before the analysis cut-off date or the date of initiation of further anti-myeloma treatment, TTP was censored at the date of the last valid disease assessment not showing disease progression performed prior to initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever comes first. As per IMWG criteria, PD was defined for participants with inc of >= 25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute inc must be >= 0.5 g/dL), serum M-protein inc >=1 g/dL if the lowest M component was >=5 g/dL; urine M-component (the absolute inc must be >=200 mg/24hour), appearance of new lesion(s), >=50% inc from nadir in SPD of >1 lesion, or >=50% inc in the longest diameter of a previous lesion >1 centimeter in short axis.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	20.27 [1]; (16.986 to NA)	NA [2]; (NA to NA)

[1]

Upper limit of the confidence interval could not be reached due to less number of participants with the progression event.

[2]

Median and the upper and lower limit of confidence interval could not be calculated because of less than 50% of the participants with the progression event.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.495
	Confidence Interval	(2-Sided) 95%; 0.324 to 0.757
	Estimation Comments	Stratification was done on the number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

14. Secondary Outcome

Title	Time to First Response: Primary Analysis
Description	Time to first response was defined as the time (in months) from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. In the absence of response, participants were censored at the earliest of the date of the last valid disease assessment before disease progression or death, the date of the last valid disease assessment before initiation of a further anti-myeloma treatment (if any) or the analysis cut-off date, whichever comes first. PR per IMWG criteria 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 randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	1.12; (1.051 to 1.183)	1.08; (1.051 to 1.117)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	1.143
	Confidence Interval	(2-Sided) 95%; 0.888 to 1.471
	Estimation Comments	[Not Specified]
Other Statistical Analysis		Stratification was done on the number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

15. Secondary Outcome

Title	Time to Best Response: Primary Analysis
Description	Time to best response was defined as time (in months) from randomization to the date of first occurrence of IRC determined as best overall response (PR or better) that is subsequently confirmed. In absence of response, participants were censored at earliest date of last valid disease assessment before disease progression/death, date of last valid disease assessment before initiation of further anti-myeloma treatment (if any)/ analysis cut-off date, whichever was 1st. PR (IMWG criteria) 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 above listed criteria, if present at baseline, a >=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required. Best Overall Response was defined as the best response, using the IRC's assessment of response, from start of treatment until disease progression, death, initiation of further anti-myeloma treatment or cut-off date, whichever occurs 1st.
Time Frame	From randomization until the primary analysis data cut-off date of 7 Feb 2020 (the median duration of follow-up was 20.73 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	3.78; (2.858 to 4.172)	4.60; (3.811 to 5.257)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not Specified]
	Type of Statistical Test	Superiority
	Comments	[Not Specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.955
	Confidence Interval	(2-Sided) 95%; 0.740 to 1.233
	Estimation Comments	Stratification was done on the number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

16. Secondary Outcome

Title	Second Progression Free Survival (PFS2): Final Analysis - Data Cut-off Date of 14 Jan 2022
Description	PFS2 defined as time (in months) from date of randomization to date of 1st documentation of PD (as assessed by investigator) after initiation of further anti-myeloma treatment /death from any cause, whichever comes 1st. Participants alive without progression after initiation of further anti-myeloma treatment before analysis cut-off date, PFS2 censored at date of last follow-up visit not showing disease progression after initiation of further anti-myeloma treatment /analysis cut-off date, whichever comes 1st. As per IMWG criteria, PD: defined for participants with increase of >= 25% from lowest confirmed value in any 1 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 longest diameter of previous lesion >1 centimeter short axis.
Time Frame	From randomization until the final analysis data cut-off date of 14 Jan 2022 (the median duration of follow-up was 43.96 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 208 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 215 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	35.58; (24.049 to 40.509)	47.18 [1]; (38.111 to NA)

[1]

Upper limit of confidence interval could not be calculated because not enough participants with PFS2 events.

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not specified]
	Type of Statistical Test	Superiority
	Comments	[Not specified]
Method of Estimation	Estimation Parameter	[Stratified Hazard Ratio]
	Estimated Value	0.683
	Confidence Interval	(2-Sided) 95%; 0.496 to 0.941
	Estimation Comments	Stratification was done on the number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

17. Secondary Outcome

Title	Second Progression Free Survival (PFS2): Overal Survival Analysis - Data Cut-off Date of 07 Feb 2023
Description	PFS2 defined as time (in months) from date of randomization to date of 1st documentation of PD (as assessed by investigator) after initiation of further anti-myeloma treatment /death from any cause, whichever comes 1st. Participants alive without progression after initiation of further anti-myeloma treatment before analysis cut-off date, PFS2 censored at date of last follow-up visit not showing disease progression after initiation of further anti-myeloma treatment /analysis cut-off date, whichever comes 1st. As per IMWG criteria, PD: defined for participants with increase of >= 25% from lowest confirmed value in any 1 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 longest diameter of previous lesion >1 centimeter short axis.
Time Frame	From randomization until the overal survival analysis data cut-off date of 07 Feb 2023 (the median duration of follow-up was 56.61 months)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Analysis was performed by Kaplan-Meier method.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 265 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 268 weeks).
Overall Number of Participants Analyzed	123	179
Median (95% Confidence Interval); Unit of Measure: months
	32.36; (23.129 to 40.016)	47.18; (38.965 to 57.922)

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Carfilzomib + Dexamethasone (Kd), Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Comments	[Not specified]
	Type of Statistical Test	Superiority
	Comments	[Not specified]
Method of Estimation	Estimation Parameter	Stratified Hazard Ratio
	Estimated Value	0.663
	Confidence Interval	(2-Sided) 95%; 0.491 to 0.895
	Estimation Comments	Stratification was done on the number of prior lines of therapy (1 vs. >1) and R-ISS stage (I or II vs. III vs. not classified) according to IRT.

18. Secondary Outcome

Title	Number of Participants With Renal Response (RR): Primary Analysis
Description	RR comprises of complete RR (CR renal), partial RR (PR renal) & minor RR (MR renal). CR renal was defined as an improvement in estimated glomerular filtration rate (eGFR) from <50 mL/min/1.73m^2 at Baseline to >=60 mL/min/1.73m^2 in at least 1 assessment during the treatment period (time from first dose of study treatment up to 30 days after last dose of study treatment); PR renal was defined as improvement in eGFR from <15 mL/min/1.73m^2 at baseline to at least 1 assessment in the range of 30 to 60 mL/min/1.73m^2 during the on-treatment-period and MR renal was defined as an improvement in eGFR from <15 mL/min/1.73m^2 at Baseline to at least 1 assessment in the range of 15 to 30 mL/min/1.73m^2 during the on-treatment-period or from 15 to 30 mL/min/1.73m^2 at Baseline to at least 1 assessment in the range of 30 to 60 mL/min/1.73m^2 during the on-treatment-period.
Time Frame	From the first dose of study treatment to 30 days following the last administration of study treatment (maximum duration: up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure and 'Number analyzed' signifies participants with available data for each specified category. Here, "0" signifies that none of the participants were available for assessment at the specified timepoint.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		13	25
Measure Type: Count of Participants; Unit of Measure: Participants
CR Renal	Number Analyzed	13 participants	25 participants
		4 30.8%	13 52.0%
PR Renal	Number Analyzed	0 participants	0 participants
MR Renal	Number Analyzed	3 participants	4 participants
		1 33.3%	4 100.0%

19. Secondary Outcome

Title	Health Related Quality of Life (HRQL): 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 Score at Specified Timepoints
Description	EORTC QLQ-C30 is a cancer-specific instrument that contains 30 items & provides multidimensional assessment of HRQL. EORTC QLQ-C30 includes global health status/quality of life (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 are 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale & are 7-point scale (1/Very Poor to 7/Excellent). GHS total score is calculated as ([{Q29+Q30}/2]-1)/6*100. Answers are converted into grading scale, with values between 0 (worse outcome) to100 (best outcome). High score represents a favorable outcome with best quality of life for participant. Results reported for primary analysis with data cut-off date 7-Feb-2020.
Time Frame	Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	99 participants	151 participants
		1.52 (21.11)	-1.60 (20.06)
Cycle 3 Day 1	Number Analyzed	100 participants	154 participants
		4.17 (22.92)	0.05 (20.29)
Cycle 4 Day 1	Number Analyzed	100 participants	150 participants
		3.58 (21.20)	-1.89 (23.71)
Cycle 5 Day 1	Number Analyzed	95 participants	149 participants
		3.60 (21.80)	-1.23 (23.12)
Cycle 6 Day 1	Number Analyzed	88 participants	145 participants
		3.13 (20.50)	-1.44 (22.12)
Cycle 7 Day 1	Number Analyzed	85 participants	141 participants
		4.22 (22.55)	-1.77 (22.38)
Cycle 8 Day 1	Number Analyzed	83 participants	134 participants
		3.82 (21.71)	-1.06 (20.78)
Cycle 9 Day 1	Number Analyzed	77 participants	128 participants
		6.60 (19.28)	-0.78 (22.17)
Cycle 10 Day 1	Number Analyzed	73 participants	124 participants
		4.91 (21.55)	-1.21 (20.35)
Cycle 11 Day 1	Number Analyzed	71 participants	121 participants
		4.34 (20.06)	-1.10 (20.18)
Cycle 12 Day 1	Number Analyzed	64 participants	119 participants
		8.59 (22.37)	0.84 (22.40)
Cycle 13 Day 1	Number Analyzed	60 participants	112 participants
		7.08 (19.76)	-1.26 (20.63)
Cycle 14 Day 1	Number Analyzed	59 participants	111 participants
		9.75 (21.62)	-0.98 (21.43)
Cycle 15 Day 1	Number Analyzed	57 participants	103 participants
		5.26 (22.14)	0.16 (20.51)
Cycle 16 Day 1	Number Analyzed	50 participants	101 participants
		6.33 (20.73)	-1.07 (20.94)
Cycle 17 Day 1	Number Analyzed	47 participants	99 participants
		7.27 (21.04)	0.00 (22.18)
Cycle 18 Day 1	Number Analyzed	45 participants	92 participants
		8.70 (23.16)	-0.36 (20.56)
Cycle 19 Day 1	Number Analyzed	41 participants	88 participants
		12.40 (21.42)	-1.23 (20.12)
Cycle 20 Day 1	Number Analyzed	34 participants	87 participants
		10.78 (20.97)	-1.05 (20.40)
Cycle 21 Day 1	Number Analyzed	28 participants	72 participants
		12.50 (21.81)	-1.85 (21.54)
Cycle 22 Day 1	Number Analyzed	19 participants	53 participants
		17.98 (22.27)	0.31 (21.24)
Cycle 23 Day 1	Number Analyzed	15 participants	37 participants
		15.56 (22.02)	3.15 (20.73)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		14.81 (26.28)	0.38 (14.88)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		15.00 (28.50)	3.13 (17.18)
End of Treatment	Number Analyzed	57 participants	56 participants
		-6.14 (22.90)	-11.90 (25.86)

20. Secondary Outcome

Title	HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score at Specified Timepoints: Primary Analysis
Description	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. It is used in conjunction with the EORTC QLQ-C30 to assess symptoms and side effects due to treatment or the disease. Disease symptoms domain is one of the four domain scores. Disease symptoms domain consist of 6 questions and the score uses 4-point scale (1 'Not at All' to 4 'Very Much'). Disease Symptoms Domain Score is calculated as ([{Q31+Q32+Q33+Q34+Q35+Q36}/6]-1)/3*100. Scores are averaged, and transformed to 0-100 scale, where higher scores = more symptoms and lower HRQL.
Time Frame	Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	103 participants	157 participants
		-5.34 (15.75)	-3.40 (19.58)
Cycle 3 Day 1	Number Analyzed	102 participants	158 participants
		-8.28 (15.33)	-7.42 (18.15)
Cycle 4 Day 1	Number Analyzed	102 participants	152 participants
		-5.45 (17.48)	-7.46 (17.99)
Cycle 5 Day 1	Number Analyzed	97 participants	150 participants
		-5.78 (17.01)	-6.37 (18.32)
Cycle 6 Day 1	Number Analyzed	91 participants	146 participants
		-6.11 (18.07)	-6.16 (19.88)
Cycle 7 Day 1	Number Analyzed	87 participants	143 participants
		-6.64 (17.44)	-4.78 (20.77)
Cycle 8 Day 1	Number Analyzed	84 participants	136 participants
		-6.94 (17.76)	-5.47 (19.96)
Cycle 9 Day 1	Number Analyzed	79 participants	131 participants
		-5.65 (18.00)	-5.51 (17.86)
Cycle 10 Day 1	Number Analyzed	74 participants	125 participants
		-5.56 (18.48)	-4.98 (17.24)
Cycle 11 Day 1	Number Analyzed	72 participants	122 participants
		-3.24 (17.78)	-7.10 (17.57)
Cycle 12 Day 1	Number Analyzed	65 participants	121 participants
		-5.30 (16.27)	-6.89 (17.58)
Cycle 13 Day 1	Number Analyzed	60 participants	114 participants
		-7.69 (17.06)	-5.95 (16.44)
Cycle 14 Day 1	Number Analyzed	59 participants	113 participants
		-8.66 (16.35)	-7.08 (17.98)
Cycle 15 Day 1	Number Analyzed	57 participants	105 participants
		-5.56 (17.69)	-5.19 (17.84)
Cycle 16 Day 1	Number Analyzed	51 participants	102 participants
		-8.06 (18.27)	-5.77 (18.66)
Cycle 17 Day 1	Number Analyzed	47 participants	101 participants
		-7.57 (19.01)	-4.29 (19.73)
Cycle 18 Day 1	Number Analyzed	45 participants	94 participants
		-7.16 (17.67)	-3.78 (17.93)
Cycle 19 Day 1	Number Analyzed	41 participants	90 participants
		-7.18 (19.57)	-3.64 (16.70)
Cycle 20 Day 1	Number Analyzed	34 participants	88 participants
		-11.93 (17.09)	-3.54 (21.63)
Cycle 21 Day 1	Number Analyzed	28 participants	73 participants
		-9.72 (16.74)	-3.81 (19.70)
Cycle 22 Day 1	Number Analyzed	19 participants	54 participants
		-9.94 (18.76)	-5.35 (22.48)
Cycle 23 Day 1	Number Analyzed	15 participants	37 participants
		-5.56 (25.11)	-6.01 (19.53)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		-6.17 (29.97)	-9.60 (18.16)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		-12.22 (28.97)	-14.58 (21.65)
End of Treatment	Number Analyzed	59 participants	57 participants
		2.35 (23.10)	1.75 (23.48)

21. Secondary Outcome

Title	HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment at Specified Timepoints: Primary Analysis
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 consists of 10 questions and the score uses a 4-point scale (1 'Not at All' to 4 'Very Much'). Side Effects of Treatment Score (MYSE) is calculated as ([{Q37+Q38+Q39+Q40+Q41+Q42+Q43+Q44+Q45+Q46}/10]-1)/3*100. 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 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	103 participants	157 participants
		1.23 (11.56)	1.41 (11.71)
Cycle 3 Day 1	Number Analyzed	102 participants	158 participants
		0.44 (10.11)	0.84 (12.00)
Cycle 4 Day 1	Number Analyzed	102 participants	152 participants
		0.83 (11.38)	0.99 (11.89)
Cycle 5 Day 1	Number Analyzed	97 participants	150 participants
		1.91 (11.36)	2.36 (11.94)
Cycle 6 Day 1	Number Analyzed	91 participants	146 participants
		2.08 (11.81)	1.61 (12.32)
Cycle 7 Day 1	Number Analyzed	87 participants	143 participants
		1.47 (12.14)	2.14 (10.76)
Cycle 8 Day 1	Number Analyzed	84 participants	136 participants
		1.53 (12.07)	2.86 (12.77)
Cycle 9 Day 1	Number Analyzed	79 participants	131 participants
		1.68 (11.57)	1.49 (11.96)
Cycle 10 Day 1	Number Analyzed	74 participants	125 participants
		2.07 (11.62)	2.68 (12.51)
Cycle 11 Day 1	Number Analyzed	72 participants	122 participants
		3.38 (12.00)	2.03 (12.16)
Cycle 12 Day 1	Number Analyzed	65 participants	121 participants
		1.20 (10.52)	3.04 (12.72)
Cycle 13 Day 1	Number Analyzed	60 participants	114 participants
		0.82 (10.22)	2.12 (12.33)
Cycle 14 Day 1	Number Analyzed	59 participants	113 participants
		1.08 (10.56)	1.71 (12.58)
Cycle 15 Day 1	Number Analyzed	57 participants	105 participants
		1.85 (11.45)	1.87 (11.80)
Cycle 16 Day 1	Number Analyzed	51 participants	102 participants
		0.99 (10.54)	2.58 (11.88)
Cycle 17 Day 1	Number Analyzed	47 participants	101 participants
		2.74 (10.03)	4.10 (12.77)
Cycle 18 Day 1	Number Analyzed	45 participants	94 participants
		2.37 (10.51)	2.95 (13.38)
Cycle 19 Day 1	Number Analyzed	41 participants	90 participants
		2.76 (11.41)	2.16 (11.56)
Cycle 20 Day 1	Number Analyzed	34 participants	88 participants
		-0.17 (10.62)	2.05 (13.03)
Cycle 21 Day 1	Number Analyzed	28 participants	73 participants
		3.17 (10.61)	2.74 (12.87)
Cycle 22 Day 1	Number Analyzed	19 participants	54 participants
		3.55 (6.46)	1.51 (12.51)
Cycle 23 Day 1	Number Analyzed	15 participants	37 participants
		7.85 (9.93)	-1.39 (12.02)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		12.35 (7.17)	-2.54 (11.33)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		11.85 (4.06)	-3.50 (12.83)
End of Treatment	Number Analyzed	59 participants	57 participants
		4.63 (13.01)	5.56 (16.22)

22. Secondary Outcome

Title	HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Body Image Score at Specified Timepoints: Primary Analysis
Description	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. It is used in conjunction with the EORTC QLQ-C30 to assess symptoms and side effects due to treatment or the disease. It consists of one question and scores are based on the 4-point Likert scale ranging from "Not at all" to "Very much". Body image score is calculated as: (1 - [Q47-1]/3)*100. Scores are averaged, and transformed to scale ranging from 0 to 100. A higher score represents a better quality of life.
Time Frame	Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	103 participants	157 participants
		-1.29 (23.76)	-1.27 (21.31)
Cycle 3 Day 1	Number Analyzed	101 participants	158 participants
		1.98 (23.01)	1.27 (26.84)
Cycle 4 Day 1	Number Analyzed	101 participants	152 participants
		-1.65 (25.55)	-1.10 (28.04)
Cycle 5 Day 1	Number Analyzed	97 participants	150 participants
		-0.69 (26.34)	-2.89 (27.29)
Cycle 6 Day 1	Number Analyzed	91 participants	146 participants
		-1.83 (24.02)	-1.60 (26.93)
Cycle 7 Day 1	Number Analyzed	87 participants	143 participants
		-0.77 (27.83)	-3.03 (24.36)
Cycle 8 Day 1	Number Analyzed	84 participants	136 participants
		-5.16 (25.08)	-0.25 (24.84)
Cycle 9 Day 1	Number Analyzed	78 participants	131 participants
		-2.14 (24.82)	-1.02 (25.80)
Cycle 10 Day 1	Number Analyzed	74 participants	125 participants
		-1.80 (25.22)	-1.33 (25.54)
Cycle 11 Day 1	Number Analyzed	72 participants	122 participants
		-1.85 (29.01)	-0.55 (23.47)
Cycle 12 Day 1	Number Analyzed	65 participants	121 participants
		-2.05 (25.60)	-0.55 (25.09)
Cycle 13 Day 1	Number Analyzed	60 participants	114 participants
		-3.89 (26.10)	-2.63 (21.79)
Cycle 14 Day 1	Number Analyzed	59 participants	113 participants
		-4.52 (26.59)	-3.24 (25.57)
Cycle 15 Day 1	Number Analyzed	57 participants	105 participants
		0.00 (25.20)	-2.22 (24.58)
Cycle 16 Day 1	Number Analyzed	51 participants	102 participants
		-1.31 (27.46)	-2.94 (22.55)
Cycle 17 Day 1	Number Analyzed	47 participants	101 participants
		-1.42 (28.62)	-1.98 (26.17)
Cycle 18 Day 1	Number Analyzed	45 participants	94 participants
		1.48 (30.11)	-1.77 (24.62)
Cycle 19 Day 1	Number Analyzed	41 participants	90 participants
		0.00 (31.62)	-3.70 (26.18)
Cycle 20 Day 1	Number Analyzed	34 participants	88 participants
		0.00 (27.22)	-0.76 (24.75)
Cycle 21 Day 1	Number Analyzed	28 participants	73 participants
		-4.76 (34.80)	-3.20 (26.74)
Cycle 22 Day 1	Number Analyzed	19 participants	54 participants
		-8.77 (36.59)	-1.85 (27.02)
Cycle 23 Day 1	Number Analyzed	15 participants	37 participants
		-13.33 (30.34)	-5.41 (24.23)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		-25.93 (36.43)	-3.03 (25.01)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		-53.33 (18.26)	-8.33 (25.82)
End of Treatment	Number Analyzed	59 participants	57 participants
		-5.65 (21.58)	-9.36 (27.28)

23. Secondary Outcome

Title	HRQL: Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 20 Items (EORTC QLQ-MY20): Future Perspective at Specified Timepoints: Primary Analysis
Description	EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. It is used in conjunction with the EORTC QLQ-C30 to assess symptoms and side effects due to treatment or the disease. It consists of three questions and the scores are based on the 4-point Likert scale ranging from "Not at all" to "Very much". Future Perspective score is calculated as (1 - ([{Q48+Q49+Q50}/3] -1)/3)*100. Scores are averaged and transformed to scale ranging from 0 to 100. A higher score represents a better quality of life.
Time Frame	Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	103 participants	157 participants
		0.54 (19.33)	7.57 (26.48)
Cycle 3 Day 1	Number Analyzed	101 participants	158 participants
		4.84 (22.08)	9.70 (24.76)
Cycle 4 Day 1	Number Analyzed	101 participants	152 participants
		6.60 (20.44)	8.55 (26.62)
Cycle 5 Day 1	Number Analyzed	97 participants	150 participants
		7.67 (22.64)	7.56 (26.98)
Cycle 6 Day 1	Number Analyzed	91 participants	146 participants
		8.42 (21.81)	9.97 (25.70)
Cycle 7 Day 1	Number Analyzed	87 participants	143 participants
		8.17 (21.93)	8.47 (24.74)
Cycle 8 Day 1	Number Analyzed	84 participants	136 participants
		7.41 (22.51)	10.54 (24.50)
Cycle 9 Day 1	Number Analyzed	78 participants	131 participants
		7.26 (21.10)	8.57 (28.26)
Cycle 10 Day 1	Number Analyzed	74 participants	125 participants
		8.56 (22.79)	11.56 (24.82)
Cycle 11 Day 1	Number Analyzed	72 participants	122 participants
		8.02 (21.69)	12.02 (24.23)
Cycle 12 Day 1	Number Analyzed	65 participants	121 participants
		6.84 (24.51)	11.48 (22.90)
Cycle 13 Day 1	Number Analyzed	60 participants	114 participants
		11.11 (20.04)	10.72 (23.18)
Cycle 14 Day 1	Number Analyzed	59 participants	113 participants
		8.85 (22.86)	11.31 (23.29)
Cycle 15 Day 1	Number Analyzed	57 participants	105 participants
		9.55 (24.16)	12.28 (22.27)
Cycle 16 Day 1	Number Analyzed	51 participants	102 participants
		12.42 (24.51)	11.76 (25.20)
Cycle 17 Day 1	Number Analyzed	47 participants	101 participants
		12.29 (21.64)	10.89 (25.29)
Cycle 18 Day 1	Number Analyzed	45 participants	94 participants
		11.36 (22.41)	7.33 (23.25)
Cycle 19 Day 1	Number Analyzed	41 participants	90 participants
		9.21 (24.96)	8.40 (25.50)
Cycle 20 Day 1	Number Analyzed	34 participants	88 participants
		10.13 (24.67)	9.60 (25.34)
Cycle 21 Day 1	Number Analyzed	28 participants	73 participants
		10.32 (22.41)	10.65 (26.15)
Cycle 22 Day 1	Number Analyzed	19 participants	54 participants
		8.77 (25.28)	12.14 (22.35)
Cycle 23 Day 1	Number Analyzed	15 participants	37 participants
		9.63 (27.81)	12.61 (20.48)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		1.23 (24.50)	16.16 (18.70)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		-4.44 (24.34)	15.28 (16.67)
End of Treatment	Number Analyzed	59 participants	57 participants
		-3.95 (22.86)	-3.70 (31.45)

24. Secondary Outcome

Title	HRQL: Change From Baseline in European Quality of Life Group Questionnaire With 5 Dimensions and 5 Levels Per Dimension (EQ-5D-5L): Health State Utility Index Value at Specified Timepoints: Primary Analysis
Description	The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health utility and consist in 2 sections a descriptive system comprising 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and Visual Analog Scale (VAS). 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. 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 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	99 participants	151 participants
		0.05 (0.17)	0.04 (0.19)
Cycle 3 Day 1	Number Analyzed	98 participants	150 participants
		0.06 (0.21)	0.05 (0.22)
Cycle 4 Day 1	Number Analyzed	99 participants	147 participants
		0.02 (0.21)	0.05 (0.21)
Cycle 5 Day 1	Number Analyzed	95 participants	144 participants
		0.04 (0.20)	0.04 (0.20)
Cycle 6 Day 1	Number Analyzed	88 participants	141 participants
		0.03 (0.19)	0.05 (0.23)
Cycle 7 Day 1	Number Analyzed	85 participants	139 participants
		0.06 (0.19)	0.04 (0.21)
Cycle 8 Day 1	Number Analyzed	81 participants	132 participants
		0.06 (0.19)	0.05 (0.22)
Cycle 9 Day 1	Number Analyzed	77 participants	124 participants
		0.05 (0.20)	0.04 (0.19)
Cycle 10 Day 1	Number Analyzed	71 participants	120 participants
		0.06 (0.22)	0.03 (0.22)
Cycle 11 Day 1	Number Analyzed	69 participants	118 participants
		0.04 (0.23)	0.05 (0.20)
Cycle 12 Day 1	Number Analyzed	63 participants	115 participants
		0.03 (0.16)	0.02 (0.20)
Cycle 13 Day 1	Number Analyzed	59 participants	109 participants
		0.06 (0.16)	0.03 (0.19)
Cycle 14 Day 1	Number Analyzed	58 participants	109 participants
		0.06 (0.24)	0.04 (0.19)
Cycle 15 Day 1	Number Analyzed	57 participants	101 participants
		0.05 (0.18)	0.05 (0.18)
Cycle 16 Day 1	Number Analyzed	50 participants	98 participants
		0.06 (0.16)	0.04 (0.19)
Cycle 17 Day 1	Number Analyzed	46 participants	97 participants
		0.05 (0.15)	0.03 (0.20)
Cycle 18 Day 1	Number Analyzed	45 participants	90 participants
		0.02 (0.15)	0.04 (0.17)
Cycle 19 Day 1	Number Analyzed	41 participants	86 participants
		0.03 (0.20)	0.03 (0.18)
Cycle 20 Day 1	Number Analyzed	34 participants	85 participants
		0.06 (0.17)	0.03 (0.23)
Cycle 21 Day 1	Number Analyzed	28 participants	70 participants
		0.03 (0.15)	0.02 (0.22)
Cycle 22 Day 1	Number Analyzed	19 participants	52 participants
		0.05 (0.19)	0.02 (0.22)
Cycle 23 Day 1	Number Analyzed	15 participants	36 participants
		0.05 (0.18)	0.00 (0.27)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		0.04 (0.24)	0.03 (0.20)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		0.05 (0.38)	0.04 (0.22)
End of Treatment	Number Analyzed	57 participants	56 participants
		-0.03 (0.25)	-0.08 (0.27)

25. Secondary Outcome

Title	HRQL: 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) at Specified Timepoints: Primary Analysis
Description	The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health utility and consist of 2 sections; descriptive system comprises 5 dimensions (mobility, self-care, usual activities, pain/discomfort and anxiety/depression) and a VAS. The VAS records the respondent's self-rated health on a 20 centimeter (cm) vertical VAS; the scale went from 0 (worst imaginable health state) to 100 (best imaginable health state). This information can be used as a quantitative measure of health as judged by the individual respondents.
Time Frame	Baseline, Day 1 of each cycle (Cycle 2 to Cycle 25), at the End of Treatment visit (any day up to 114 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population. Here, 'Number analyzed' signifies participants with available data for each specified category.

Arm/Group Title		Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 114 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		123	179
Mean (Standard Deviation); Unit of Measure: score on a scale
Cycle 2 Day 1	Number Analyzed	99 participants	151 participants
		2.42 (17.04)	0.60 (15.23)
Cycle 3 Day 1	Number Analyzed	98 participants	150 participants
		4.70 (16.13)	3.47 (17.80)
Cycle 4 Day 1	Number Analyzed	99 participants	147 participants
		6.03 (16.73)	2.29 (18.69)
Cycle 5 Day 1	Number Analyzed	94 participants	144 participants
		3.40 (16.89)	2.35 (19.73)
Cycle 6 Day 1	Number Analyzed	88 participants	141 participants
		2.80 (18.56)	1.24 (19.11)
Cycle 7 Day 1	Number Analyzed	84 participants	139 participants
		0.64 (21.69)	2.24 (18.85)
Cycle 8 Day 1	Number Analyzed	81 participants	132 participants
		1.48 (17.11)	2.40 (18.87)
Cycle 9 Day 1	Number Analyzed	77 participants	124 participants
		-0.14 (17.46)	2.93 (19.04)
Cycle 10 Day 1	Number Analyzed	71 participants	120 participants
		2.76 (17.41)	2.82 (18.35)
Cycle 11 Day 1	Number Analyzed	69 participants	118 participants
		3.86 (20.07)	3.77 (18.51)
Cycle 12 Day 1	Number Analyzed	63 participants	115 participants
		5.29 (18.51)	3.63 (19.34)
Cycle 13 Day 1	Number Analyzed	59 participants	109 participants
		6.81 (19.57)	4.94 (18.41)
Cycle 14 Day 1	Number Analyzed	58 participants	109 participants
		7.95 (18.12)	4.72 (17.67)
Cycle 15 Day 1	Number Analyzed	57 participants	101 participants
		4.96 (18.92)	3.23 (18.87)
Cycle 16 Day 1	Number Analyzed	50 participants	98 participants
		3.94 (18.78)	4.56 (18.88)
Cycle 17 Day 1	Number Analyzed	46 participants	97 participants
		5.04 (17.93)	4.97 (18.55)
Cycle 18 Day 1	Number Analyzed	45 participants	90 participants
		3.71 (19.08)	3.83 (18.46)
Cycle 19 Day 1	Number Analyzed	41 participants	86 participants
		7.44 (18.73)	3.69 (18.37)
Cycle 20 Day 1	Number Analyzed	34 participants	85 participants
		6.18 (18.43)	4.20 (17.20)
Cycle 21 Day 1	Number Analyzed	28 participants	70 participants
		7.25 (23.46)	3.26 (18.97)
Cycle 22 Day 1	Number Analyzed	19 participants	52 participants
		5.58 (24.06)	2.35 (18.62)
Cycle 23 Day 1	Number Analyzed	15 participants	36 participants
		6.33 (18.73)	6.44 (18.34)
Cycle 24 Day 1	Number Analyzed	9 participants	22 participants
		5.11 (17.93)	4.50 (18.31)
Cycle 25 Day 1	Number Analyzed	5 participants	16 participants
		9.20 (21.48)	5.00 (18.83)
End of Treatment	Number Analyzed	57 participants	56 participants
		-4.40 (18.66)	-7.80 (21.08)

26. Secondary Outcome

Title	Pharmacokinetics: Plasma Concentration at End of Infusion (Ceoi) of Isatuximab: Primary Analysis
Description	Ceoi is the plasma concentration observed at the end of intravenous infusion.
Time Frame	End of infusion on Cycle 1 Day 1 and Cycle 1 Day 15; Cycle 2 Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		172
Mean (Standard Deviation); Unit of Measure: microgram/milliliter (mcg/mL)
Cycle 1 Day 1	Number Analyzed	169 participants
		274.01 (183.67)
Cycle 1 Day 15	Number Analyzed	27 participants
		380.28 (85.70)
Cycle 2 Day 1	Number Analyzed	161 participants
		522.74 (204.11)

27. Secondary Outcome

Title	Pharmacokinetics: Plasma Concentration of Isatuximab at Ctrough: Primary Analysis
Description	Ctrough was the plasma concentration observed just before treatment administration during repeated dosing.
Time Frame	Pre-infusion on Cycle 1 Day 1, Day 8, Day 15 and Day 22, Cycle 2 Day 1, Cycle 3 Day 1, Cycle 4 Day 1, Cycle 5 Day 1, Cycle 6 Day 1, Cycle 7 Day 1, Cycle 8 Day 1, Cycle 9 Day 1 and Cycle 10 Day 1

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title		Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:		Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed		172
Mean (Standard Deviation); Unit of Measure: mcg/mL
Cycle 1 Day 1	Number Analyzed	166 participants
		3.66 (34.40)
Cycle 1 Day 8	Number Analyzed	152 participants
		82.14 (43.87)
Cycle 1 Day 15	Number Analyzed	144 participants
		180.02 (71.83)
Cycle 1 Day 22	Number Analyzed	147 participants
		252.63 (100.16)
Cycle 2 Day 1	Number Analyzed	130 participants
		324.28 (132.98)
Cycle 3 Day 1	Number Analyzed	145 participants
		295.78 (146.11)
Cycle 4 Day 1	Number Analyzed	137 participants
		342.48 (140.94)
Cycle 5 Day 1	Number Analyzed	135 participants
		389.25 (172.11)
Cycle 6 Day 1	Number Analyzed	130 participants
		427.16 (188.51)
Cycle 7 Day 1	Number Analyzed	123 participants
		433.22 (177.11)
Cycle 8 Day 1	Number Analyzed	118 participants
		490.51 (198.17)
Cycle 9 Day 1	Number Analyzed	113 participants
		486.07 (181.34)
Cycle 10 Day 1	Number Analyzed	100 participants
		490.08 (206.53)

28. Secondary Outcome

Title	Pharmacokinetics: Maximum Observed Concentration (Cmax) of Carfilzomib: Primary Analysis
Description	Cmax was defined as the maximum concentration observed after the first infusion calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 minutes (min), 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: nanogram/milliliter (ng/mL)
	2090 (1360)

29. Secondary Outcome

Title	Pharmacokinetics: Clast of Carfilzomib: Primary Analysis
Description	Clast was defined as the last concentration observed above the lower limit of quantification.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: ng/mL
	3.00 (5.11)

30. Secondary Outcome

Title	Pharmacokinetics: Tmax of Carfilzomib: Primary Analysis
Description	Tmax was defined as the time to reach Cmax, calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Median (Full Range); Unit of Measure: hours
	0.54; (0.35 to 0.75)

31. Secondary Outcome

Title	Pharmacokinetics: Tlast of Carfilzomib: Primary Analysis
Description	Tlast was defined as the time of last concentration observed above the lower limit of quantification, calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Median (Full Range); Unit of Measure: hours
	4.50; (2.52 to 4.75)

32. Secondary Outcome

Title	Pharmacokinetics: Area Under the Plasma Concentration Time Curve (AUC) of Carfilzomib: Primary Analysis
Description	AUC was defined as area under the plasma concentration-time curve extrapolated to infinity according to the equation: AUC= AUClast + Clast/λz. AUC was calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: nanograms*hour/milliliter(ng*h/mL)
	784 (509)

33. Secondary Outcome

Title	Pharmacokinetics: Area Under the Plasma Concentration Time Curve From Time 0 to Last Quantifiable Concentration (AUClast) of Carfilzomib: Primary Analysis
Description	AUClast was defined as area under the plasma concentration versus time curve calculated from time 0 to last quantifiable concentration. AUClast was calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: ng*h/mL
	779 (505)

34. Secondary Outcome

Title	Pharmacokinetics: Percentage of Extrapolation of AUC (AUCext) of Carfilzomib: Primary Analysis
Description	AUCext was defined as the percentage of the extrapolation of AUC, calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Geometric Mean (Geometric Coefficient of Variation); Unit of Measure: percentage of AUC
	0; (172%)

35. Secondary Outcome

Title	Pharmacokinetics: Terminal Half-life (t1/2z) of Carfilzomib: Primary Analysis
Description	T1/2 was defined as the time required for the concentration of the drug to reach half of its original value, calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Median (Full Range); Unit of Measure: hours
	0.860; (0.450 to 1.89)

36. Secondary Outcome

Title	Pharmacokinetics: Clearance at Steady State (CLss) of Carfilzomib: Primary Analysis
Description	CLss was defined as a quantitative measure of the rate at which a drug substance is removed from the body at steady state, calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: Liters/hour (L/h)
	466 (1190)

37. Secondary Outcome

Title	Pharmacokinetics: Volume of Distribution at Steady State (Vss) of Carfilzomib: Primary Analysis
Description	Volume of Distribution was defined as the theoretical volume in which the total amount of drug would need to be uniformly distributed to produce the desired plasma concentration of a drug. Vss is the apparent volume of distribution at steady-state, calculated using the non-compartmental analysis after the intravenous infusion of carfilzomib with isatuximab.
Time Frame	Cycle 1: pre-dose (0 hour), 30 min, 35 min, 45 min, 60 min, 1 hour 30 min, 2 hours 30 min and 4 hours 30 min post-dose on Day 15

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population. Data for this OM was not planned to be collected and analyzed for Kd arm. Here, 'overall number of participants analyzed' = participants with available data for this outcome measure.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	16
Mean (Standard Deviation); Unit of Measure: Liters
	453 (1570)

38. Secondary Outcome

Title	Number of Participants With Anti-Drug Antibodies (ADA): Primary Analysis
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 pre-existing ADA, including participants without pretreatment samples. Treatment boosted ADA was defined as pre-existing ADA with an increase in titer during the ADA on-study observation period.
Time Frame	From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: 111 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 IKd arm with at least one ADA assessment during the ADA on-study observation period with a reportable result. Data for this outcome measure was not planned to be collected and analyzed for Kd arm.

Arm/Group Title	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 111 weeks).
Overall Number of Participants Analyzed	168
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%

39. Secondary Outcome

Title	Number of Participants With Treatment-emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs): Final Analysis
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, 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 was any untoward medical occurrence that at any dose: resulted in death, was life-threatening, required inpatient hospitalization or prolongation of existing hospitalization, resulted in persistent or significant disability / incapacity, was a congenital anomaly/birth defect, was a medically important event.
Time Frame	From first dose of study treatment up to 30 days after last dose of study treatment (maximum duration: up to 265 weeks for Kd arm and 268 weeks for IKd arm)

Outcome Measure Data

Analysis Population Description

Analysis was performed on safety population which included all who gave their informed consent and for whom there was confirmation of successful allocation of a randomization number by the IRT and received at least one dose or a part of a dose of the study treatments.

Arm/Group Title	Carfilzomib + Dexamethasone (Kd)	Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description:	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle along with dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 265 weeks).	Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, and then on Days 1 and Day 15 of each 28-day treatment cycle plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and then on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycle and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycle until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 268 weeks).
Overall Number of Participants Analyzed	122	177
Measure Type: Count of Participants; Unit of Measure: Participants
Any TEAE	119 97.5%	175 98.9%
Any treatment emergent SAE	74 60.7%	126 71.2%

Adverse Events

Time Frame	AE data was collected from the time of first dose of study treatment to 30 days following the last administration of study treatment (up to 265 weeks for Kd arm and 268 weeks for IKd 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 treatment). All-Cause Mortality data collected during the study was assessed for all randomized participants. Serious and Other Adverse Events were collected for safety population only.
Arm/Group Title	Carfilzomib + Dexamethasone (Kd)		Isatuximab + Carfilzomib + Dexamethasone (IKd)
Arm/Group Description	Participants received carfilzomib 20 mg/m^2, IV infusion on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycles plus dexamethasone 20 mg, PO or IV on Days 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycles until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 265 weeks).		Participants received isatuximab 10 mg/kg, IV infusion on Days 1, 8, 15 and 22 in Cycle 1, then on Days 1 and Day 15 of each 28-day treatment cycles plus carfilzomib 20 mg/m^2, IV on Days 1, and 2 in Cycle 1, and then escalated to 56 mg/m^2 on Days 8, 9, 15 and 16 of Cycle 1 and on Days 1, 2, 8, 9, 15 and 16 of each subsequent 28-day treatment cycles and dexamethasone 20 mg, PO or IV on Day 1, 2, 8, 9, 15, 16, 22 and 23 of each 28-day treatment cycles until disease progression or unacceptable adverse event or participant's decision to discontinue the study treatment or any other reason, whichever comes first (maximum exposure: 268 weeks).
All-Cause Mortality
	Carfilzomib + Dexamethasone (Kd)		Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Affected / at Risk (%)		Affected / at Risk (%)
Total	59/123 (47.97%)		79/179 (44.13%)
Serious Adverse Events
	Carfilzomib + Dexamethasone (Kd)		Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	74/122 (60.66%)		126/177 (71.19%)
Blood and lymphatic system disorders
Anaemia † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Febrile Neutropenia † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Normocytic Anaemia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Thrombocytopenia † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Cardiac disorders
Acute Coronary Syndrome † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Acute Myocardial Infarction † 1	2/122 (1.64%)	3	1/177 (0.56%)	1
Angina Pectoris † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Aortic Valve Stenosis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Arteriosclerosis Coronary Artery † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Atrial Fibrillation † 1	0/122 (0.00%)	0	3/177 (1.69%)	3
Cardiac Failure † 1	4/122 (3.28%)	4	4/177 (2.26%)	5
Cardiac Failure Acute † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Cardiac Failure Chronic † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Cardiac Failure Congestive † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Cardiac Hypertrophy † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Coronary Artery Insufficiency † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Coronary Artery Stenosis † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Left Ventricular Failure † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Supraventricular Tachycardia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Tachycardia † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Ear and labyrinth disorders
Deafness Neurosensory † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Vertigo † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Eye disorders
Cataract † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Gastrointestinal disorders
Anal Haemorrhage † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Colitis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Colitis Ischaemic † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Diarrhoea † 1	2/122 (1.64%)	3	2/177 (1.13%)	2
Duodenal Ulcer Haemorrhage † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Gastrointestinal Haemorrhage † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Haemorrhoids † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Ileal Perforation † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Large Intestine Perforation † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Lower Gastrointestinal Haemorrhage † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pancreatitis Acute † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Umbilical Hernia † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Vomiting † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
General disorders
Death † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Disease Progression † 1	2/122 (1.64%)	2	1/177 (0.56%)	1
General Physical Health Deterioration † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Injection Site Extravasation † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Malaise † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Non-Cardiac Chest Pain † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Peripheral Swelling † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pyrexia † 1	3/122 (2.46%)	3	4/177 (2.26%)	4
Hepatobiliary disorders
Cholecystitis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Immune system disorders
Drug Hypersensitivity † 1	2/122 (1.64%)	2	0/177 (0.00%)	0
Infections and infestations
Abdominal Abscess † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Abdominal Sepsis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Appendicitis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Atypical Pneumonia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Bacterial Sepsis † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Bronchitis † 1	1/122 (0.82%)	1	3/177 (1.69%)	3
Bronchitis Pneumococcal † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Covid-19 † 1	1/122 (0.82%)	2	5/177 (2.82%)	5
Covid-19 Pneumonia † 1	2/122 (1.64%)	2	3/177 (1.69%)	3
Campylobacter Gastroenteritis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Cellulitis † 1	2/122 (1.64%)	3	3/177 (1.69%)	3
Clostridium Difficile Colitis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Cytomegalovirus Viraemia † 1	0/122 (0.00%)	0	1/177 (0.56%)	2
Device Related Bacteraemia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Device Related Infection † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Diverticulitis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Erysipelas † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Escherichia Pyelonephritis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Gastroenteritis † 1	2/122 (1.64%)	3	2/177 (1.13%)	2
Gastroenteritis Salmonella † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
H1n1 Influenza † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
H3n2 Influenza † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Haematoma Infection † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Hepatitis B † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Influenza † 1	5/122 (4.10%)	5	2/177 (1.13%)	2
Liver Abscess † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Lower Respiratory Tract Infection † 1	6/122 (4.92%)	12	8/177 (4.52%)	8
Lower Respiratory Tract Infection Viral † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Metapneumovirus Pneumonia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Osteomyelitis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Parainfluenzae Virus Infection † 1	1/122 (0.82%)	1	2/177 (1.13%)	2
Phlebitis Infective † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Pleurisy Bacterial † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pneumocystis Jirovecii Pneumonia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pneumonia † 1	17/122 (13.93%)	19	37/177 (20.90%)	50
Pneumonia Influenzal † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pneumonia Legionella † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pneumonia Pneumococcal † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Pneumonia Respiratory Syncytial Viral † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Pneumonia Streptococcal † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pneumonia Viral † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Pulmonary Sepsis † 1	1/122 (0.82%)	1	2/177 (1.13%)	2
Respiratory Syncytial Virus Bronchitis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Respiratory Syncytial Virus Infection † 1	0/122 (0.00%)	0	3/177 (1.69%)	3
Respiratory Tract Infection † 1	1/122 (0.82%)	1	4/177 (2.26%)	4
Salmonellosis † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Sepsis † 1	1/122 (0.82%)	1	4/177 (2.26%)	4
Septic Shock † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Sinusitis † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Skin Infection † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Tracheobronchitis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Upper Respiratory Tract Infection † 1	2/122 (1.64%)	2	6/177 (3.39%)	6
Urinary Tract Infection † 1	1/122 (0.82%)	1	2/177 (1.13%)	2
Urinary Tract Infection Bacterial † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Vascular Device Infection † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Viral Upper Respiratory Tract Infection † 1	0/122 (0.00%)	0	3/177 (1.69%)	3
Visceral Leishmaniasis † 1	0/122 (0.00%)	0	1/177 (0.56%)	2
Injury, poisoning and procedural complications
Anaemia Postoperative † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Brain Contusion † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Contusion † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Facial Bones Fracture † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Fall † 1	0/122 (0.00%)	0	4/177 (2.26%)	4
Hip Fracture † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Infusion Related Reaction † 1	0/122 (0.00%)	0	3/177 (1.69%)	3
Multiple Injuries † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Road Traffic Accident † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Skin Injury † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Traumatic Fracture † 1	2/122 (1.64%)	2	5/177 (2.82%)	5
Investigations
Blood Creatinine Increased † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Bone Marrow Plasmacyte Count Increased † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Electrocardiogram T Wave Inversion † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Grip Strength Decreased † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Plasma Cells Increased † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Metabolism and nutrition disorders
Diabetes Mellitus † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Hypercalcaemia † 1	1/122 (0.82%)	1	3/177 (1.69%)	3
Hyperglycaemia † 1	1/122 (0.82%)	1	2/177 (1.13%)	2
Mineral Metabolism Disorder † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Tumour Lysis Syndrome † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Type 2 Diabetes Mellitus † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Musculoskeletal and connective tissue disorders
Arthralgia † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Back Pain † 1	1/122 (0.82%)	1	3/177 (1.69%)	3
Chondrocalcinosis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Haemarthrosis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Intervertebral Disc Protrusion † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Musculoskeletal Chest Pain † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Osteoarthritis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Osteonecrosis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Osteonecrosis Of Jaw † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Pain In Extremity † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Pathological Fracture † 1	1/122 (0.82%)	1	5/177 (2.82%)	5
Rheumatoid Arthritis † 1	0/122 (0.00%)	0	1/177 (0.56%)	2
Sympathetic Posterior Cervical Syndrome † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Anal Squamous Cell Carcinoma † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Basal Cell Carcinoma † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Bowen's Disease † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Breast Cancer Female † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Colon Cancer † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Colorectal Cancer Stage I † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Large Cell Lung Cancer † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Lung Neoplasm Malignant † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Lung Squamous Cell Carcinoma Stage Ii † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Pancreatic Carcinoma Metastatic † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Plasma Cell Leukaemia † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Second Primary Malignancy † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Squamous Cell Carcinoma Of Skin † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Uterine Cancer † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Nervous system disorders
Dementia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Embolic Cerebral Infarction † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Encephalopathy † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Hypoaesthesia † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Intracranial Mass † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Ischaemic Stroke † 1	2/122 (1.64%)	2	1/177 (0.56%)	1
Peripheral Nerve Paresis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Presyncope † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Subarachnoid Haemorrhage † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Syncope † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Product Issues
Device Malfunction † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Renal and urinary disorders
Acute Kidney Injury † 1	5/122 (4.10%)	7	3/177 (1.69%)	3
Calculus Urinary † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Nephrotic Syndrome † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Renal Colic † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Renal Failure † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Reproductive system and breast disorders
Acquired Phimosis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Benign Prostatic Hyperplasia † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Respiratory, thoracic and mediastinal disorders
Asthma † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Bronchiectasis † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Chronic Obstructive Pulmonary Disease † 1	2/122 (1.64%)	4	2/177 (1.13%)	2
Dyspnoea † 1	0/122 (0.00%)	0	2/177 (1.13%)	2
Pulmonary Embolism † 1	2/122 (1.64%)	2	3/177 (1.69%)	3
Pulmonary Hypertension † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Pulmonary Oedema † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Skin and subcutaneous tissue disorders
Diabetic Foot † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Drug Eruption † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
Vascular disorders
Deep Vein Thrombosis † 1	4/122 (3.28%)	4	3/177 (1.69%)	3
Extremity Necrosis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Hypertension † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Hypertensive Crisis † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Hypotension † 1	1/122 (0.82%)	1	1/177 (0.56%)	1
Peripheral Arterial Occlusive Disease † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Vasculitis † 1	1/122 (0.82%)	1	0/177 (0.00%)	0
Venous Thrombosis Limb † 1	0/122 (0.00%)	0	1/177 (0.56%)	1
1 Term from vocabulary, MedDra 25.1; † Indicates events were collected by systematic assessment
Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events	5%
	Carfilzomib + Dexamethasone (Kd)		Isatuximab + Carfilzomib + Dexamethasone (IKd)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	113/122 (92.62%)		167/177 (94.35%)
Blood and lymphatic system disorders
Neutropenia † 1	1/122 (0.82%)	1	11/177 (6.21%)	19
Thrombocytopenia † 1	11/122 (9.02%)	13	5/177 (2.82%)	5
Eye disorders
Cataract † 1	11/122 (9.02%)	11	31/177 (17.51%)	37
Gastrointestinal disorders
Abdominal Pain † 1	9/122 (7.38%)	10	8/177 (4.52%)	11
Constipation † 1	13/122 (10.66%)	17	24/177 (13.56%)	32
Diarrhoea † 1	38/122 (31.15%)	55	69/177 (38.98%)	128
Dyspepsia † 1	5/122 (4.10%)	5	17/177 (9.60%)	25
Gastrooesophageal Reflux Disease † 1	5/122 (4.10%)	5	12/177 (6.78%)	12
Nausea † 1	22/122 (18.03%)	35	36/177 (20.34%)	75
Vomiting † 1	13/122 (10.66%)	25	28/177 (15.82%)	43
General disorders
Asthenia † 1	21/122 (17.21%)	30	36/177 (20.34%)	70
Fatigue † 1	25/122 (20.49%)	29	56/177 (31.64%)	80
Influenza Like Illness † 1	5/122 (4.10%)	9	9/177 (5.08%)	11
Non-Cardiac Chest Pain † 1	7/122 (5.74%)	8	12/177 (6.78%)	12
Oedema Peripheral † 1	21/122 (17.21%)	30	29/177 (16.38%)	47
Pyrexia † 1	21/122 (17.21%)	31	21/177 (11.86%)	30
Infections and infestations
Bronchitis † 1	14/122 (11.48%)	22	43/177 (24.29%)	69
Covid-19 † 1	2/122 (1.64%)	2	23/177 (12.99%)	26
Conjunctivitis † 1	9/122 (7.38%)	13	12/177 (6.78%)	13
Gastroenteritis † 1	7/122 (5.74%)	7	19/177 (10.73%)	23
Influenza † 1	13/122 (10.66%)	26	20/177 (11.30%)	27
Lower Respiratory Tract Infection † 1	8/122 (6.56%)	12	11/177 (6.21%)	15
Nasopharyngitis † 1	16/122 (13.11%)	30	36/177 (20.34%)	49
Pneumonia † 1	13/122 (10.66%)	21	15/177 (8.47%)	17
Respiratory Tract Infection † 1	7/122 (5.74%)	10	19/177 (10.73%)	46
Rhinitis † 1	3/122 (2.46%)	4	11/177 (6.21%)	18
Sinusitis † 1	5/122 (4.10%)	8	12/177 (6.78%)	18
Upper Respiratory Tract Infection † 1	32/122 (26.23%)	51	71/177 (40.11%)	166
Urinary Tract Infection † 1	11/122 (9.02%)	21	18/177 (10.17%)	30
Injury, poisoning and procedural complications
Accidental Overdose † 1	7/122 (5.74%)	8	17/177 (9.60%)	41
Contusion † 1	6/122 (4.92%)	13	12/177 (6.78%)	19
Fall † 1	12/122 (9.84%)	23	21/177 (11.86%)	29
Infusion Related Reaction † 1	4/122 (3.28%)	6	80/177 (45.20%)	122
Limb Injury † 1	3/122 (2.46%)	5	11/177 (6.21%)	12
Skin Laceration † 1	3/122 (2.46%)	7	10/177 (5.65%)	32
Traumatic Fracture † 1	4/122 (3.28%)	5	12/177 (6.78%)	13
Investigations
Weight Decreased † 1	1/122 (0.82%)	1	11/177 (6.21%)	11
Metabolism and nutrition disorders
Decreased Appetite † 1	5/122 (4.10%)	5	14/177 (7.91%)	18
Musculoskeletal and connective tissue disorders
Arthralgia † 1	14/122 (11.48%)	20	42/177 (23.73%)	63
Back Pain † 1	25/122 (20.49%)	34	43/177 (24.29%)	60
Bone Pain † 1	9/122 (7.38%)	12	14/177 (7.91%)	17
Muscle Spasms † 1	19/122 (15.57%)	26	28/177 (15.82%)	41
Muscular Weakness † 1	11/122 (9.02%)	14	6/177 (3.39%)	7
Musculoskeletal Chest Pain † 1	8/122 (6.56%)	9	10/177 (5.65%)	11
Myalgia † 1	6/122 (4.92%)	7	11/177 (6.21%)	11
Pain In Extremity † 1	17/122 (13.93%)	20	27/177 (15.25%)	35
Nervous system disorders
Dizziness † 1	7/122 (5.74%)	11	9/177 (5.08%)	13
Headache † 1	22/122 (18.03%)	41	30/177 (16.95%)	43
Peripheral Sensory Neuropathy † 1	16/122 (13.11%)	24	29/177 (16.38%)	35
Psychiatric disorders
Anxiety † 1	4/122 (3.28%)	5	15/177 (8.47%)	18
Insomnia † 1	30/122 (24.59%)	43	45/177 (25.42%)	52
Respiratory, thoracic and mediastinal disorders
Cough † 1	18/122 (14.75%)	27	40/177 (22.60%)	63
Dyspnoea † 1	27/122 (22.13%)	41	54/177 (30.51%)	75
Productive Cough † 1	2/122 (1.64%)	2	9/177 (5.08%)	10
Skin and subcutaneous tissue disorders
Erythema † 1	2/122 (1.64%)	2	9/177 (5.08%)	12
Rash † 1	9/122 (7.38%)	9	13/177 (7.34%)	15
Vascular disorders
Deep Vein Thrombosis † 1	8/122 (6.56%)	9	8/177 (4.52%)	12
Hypertension † 1	42/122 (34.43%)	66	69/177 (38.98%)	107
Superficial Vein Thrombosis † 1	7/122 (5.74%)	12	10/177 (5.65%)	13
1 Term from vocabulary, MedDra 25.1; † 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 of Results:

Moreau P, Dimopoulos MA, Mikhael J, Yong K, Capra M, Facon T, Hajek R, Spicka I, Baker R, Kim K, Martinez G, Min CK, Pour L, Leleu X, Oriol A, Koh Y, Suzuki K, Risse ML, Asset G, Mace S, Martin T; IKEMA study group. Isatuximab, carfilzomib, and dexamethasone in relapsed multiple myeloma (IKEMA): a multicentre, open-label, randomised phase 3 trial. Lancet. 2021 Jun 19;397(10292):2361-2371. doi: 10.1016/S0140-6736(21)00592-4. Epub 2021 Jun 4.

Martin TG, Capra M, Mohty M, Suzuki K, Quach H, Cavo M, Moreau P, Dimopoulos M, Yong K, Tekle C, Foster MC, Barnes Y, Risse ML, Mikhael J. Isatuximab Plus Carfilzomib and Dexamethasone Versus Carfilzomib and Dexamethasone in Patients with Relapsed Multiple Myeloma: IKEMA Subgroup Analysis by Prior Transplantation. Transplant Cell Ther. 2023 Feb;29(2):134.e1-134.e7. doi: 10.1016/j.jtct.2022.11.005. Epub 2022 Nov 11.

Chami B, Okuda M, Moayeri M, Pirenne F, Hidaka Y, Nambiar A, Song Z, Bedel O, Zhang B, Hopke J, Deng G, Zhu C, Mace S, Chiron M, Adrian F, Fukao T, Basile FG, Martin T. Anti-CD38 monoclonal antibody interference with blood compatibility testing: Differentiating isatuximab and daratumumab via functional epitope mapping. Transfusion. 2022 Nov;62(11):2334-2348. doi: 10.1111/trf.17137. Epub 2022 Oct 14.

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

Moreau P, Dimopoulos MA, Yong K, Mikhael J, Risse ML, Asset G, Martin T. Isatuximab plus carfilzomib/dexamethasone versus carfilzomib/dexamethasone in patients with relapsed/refractory multiple myeloma: IKEMA Phase III study design. Future Oncol. 2020 Jan;16(2):4347-4358. doi: 10.2217/fon-2019-0431. Epub 2019 Dec 13.

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT03275285
• Other Study ID Numbers: EFC15246; U1111-1195-5957 ( Registry Identifier: ICTRP ); 2017-001940-37 ( EudraCT Number )
• First Submitted: September 5, 2017
• First Posted: September 7, 2017
• Results First Submitted: January 13, 2023
• Results First Posted: February 13, 2023
• Last Update Posted: February 20, 2024