Trial Outcomes & Findings for Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients (NCT NCT02990338)

Last Updated: 2025-01-17

Results Overview

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

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

307 participants

Primary outcome timeframe

From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks)

Results posted on

2025-01-17

Participant Flow

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

Randomization was stratified by age (less than \[\<\] 75 years versus greater than and equal to \[\>=\] 75 years) and number of previous lines of therapy (2 or 3 versus more than 3). "Reason for not completed" = "Reason for definitive treatment discontinuation."

Participant milestones

Participant milestones
Measure	Pd (Pomalidomide + Dexamethasone) Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 306.6 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 311.0 weeks).
Overall Study STARTED	153	154
Overall Study Treated	149	152
Overall Study COMPLETED	0	0
Overall Study NOT COMPLETED	153	154

Reasons for withdrawal

Reasons for withdrawal
Measure	Pd (Pomalidomide + Dexamethasone) Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 306.6 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 311.0 weeks).
Overall Study Randomized and not treated	4	2
Overall Study Adverse Event	23	22
Overall Study Progressive disease	118	107
Overall Study Poor compliance to protocol	0	1
Overall Study Withdrawal by Subject	6	8
Overall Study Physician's decision	2	6
Overall Study Treatment extension study	0	6
Overall Study Unconfirmed disease progression per investigator	0	1
Overall Study Continue with therapy available commercially	0	1

Baseline Characteristics

Multinational Clinical Study Comparing Isatuximab, Pomalidomide, and Dexamethasone to Pomalidomide and Dexamethasone in Refractory or Relapsed and Refractory Multiple Myeloma Patients

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 306.6 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 311.0 weeks).	Total n=307 Participants Total of all reporting groups
Age, Continuous	65.2 years STANDARD_DEVIATION 9.5 • n=5 Participants	66.6 years STANDARD_DEVIATION 9.1 • n=7 Participants	65.9 years STANDARD_DEVIATION 9.3 • n=5 Participants
Sex: Female, Male Female	83 Participants n=5 Participants	65 Participants n=7 Participants	148 Participants n=5 Participants
Sex: Female, Male Male	70 Participants n=5 Participants	89 Participants n=7 Participants	159 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	15 Participants n=5 Participants	21 Participants n=7 Participants	36 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	1 Participants n=5 Participants	2 Participants n=7 Participants	3 Participants n=5 Participants
Race (NIH/OMB) Black or African American	3 Participants n=5 Participants	1 Participants n=7 Participants	4 Participants n=5 Participants
Race (NIH/OMB) White	126 Participants n=5 Participants	118 Participants n=7 Participants	244 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	8 Participants n=5 Participants	12 Participants n=7 Participants	20 Participants n=5 Participants

PRIMARY outcome

Timeframe: From the date of randomization to the date of first documentation of progression, or the date of death from any cause, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration: 76.7 weeks)

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

Outcome measures

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

SECONDARY outcome

Timeframe: From the date of randomization to the date of first documentation of progression or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

ORR (IMWG criteria): percentage of participants with stringent complete response(sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) as best overall response, assessed by IRC. sCR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,\<5% plasma cells in bone marrow aspirates plus normal free light chain(FLC)ratio(0.26-1.65), absence of clonal cells in bone marrow biopsy.CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,\<5% plasma cells in bone marrow aspirates.VGPR: serum and urine M-protein detectable by immunofixation, not on electrophoresis/,\>=90% reduction in serum M-protein plus urine M-protein level \<100mg/24h/,\>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: \>=50% reduction of serum M-protein and reduction in 24h urinary M-protein by \>=90%/\<200mg/24h,if present at baseline,\>=50% reduction in the size (SPD) of soft tissue plasmacytomas.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC)	35.3 percentage of participants	60.4 percentage of participants

SECONDARY outcome

Timeframe: From the date of randomization until disease progression, or death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

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

Outcome measures

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

SECONDARY outcome

Timeframe: From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment, or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

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

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee	8.5 percentage of participants	31.8 percentage of participants

SECONDARY outcome

Timeframe: From the date of randomization to the date of first documentation of progression, death, initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

CBR was defined as the percentage of participants achieving a MR or better as BOR. MR was defined as \>= 25% but \<= 49% reduction in serum M-protein and reduction in 24h urine M-protein by 50-89%, which still exceed 200 mg/24h; if present at baseline, \>=50% reduction in size (SPD) of soft tissue plasmacytomas was also required. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee	46.4 percentage of participants	66.9 percentage of participants

SECONDARY outcome

Timeframe: From the date of randomization to date of death from any cause or data cut-off date, whichever was earlier (maximum duration 245.6 weeks)

Population: Analysis was performed on ITT population.

OS was defined as the time from the date of randomization to death from any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive or at the cut-off date, whichever comes first. This pre-specified final analysis was performed when the 220 OS events were met.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Overall Survival (OS): Final Analysis	17.71 months Interval 14.39 to 26.218	24.57 months Interval 20.304 to 31.31

SECONDARY outcome

Timeframe: From the date of randomization to the date of first documentation of progression, or initiation of further anti-myeloma treatment or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

TTP was defined as time from randomization to the date of first documentation of PD, as determined by the IRC. As per IMWG criteria, PD was defined for participants with increase of \>= 25% from lowest confirmed value in any one of the following criteria: serum M-protein (the absolute increase must be \>= 0.5 g/dL), serum M-protein increase \>=1 g/dL if the lowest M component was \>=5 g/dL; urine M-component (the absolute increase must be \>=200 mg/24hour), appearance of new lesion(s), \>=50% increase from nadir in SPD of \>1 lesion, or \>=50% increase in the longest diameter of a previous lesion \>1 centimeter in short axis.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Time to Progression (TTP) as Per Independent Response Committee	7.75 months Interval 5.027 to 9.758	12.71 months Interval 11.203 to 15.211

SECONDARY outcome

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

PFS in high risk cytogenetic population was defined as PFS in subgroup of participants carrying high risk cytogenetic changes including del(17p), translocation (t)(4;14) or translocation t(14;16) assessed by fluorescence in situ hybridization (FISH). PFS was defined as the time from date of randomization to date of first documentation of PD (determined by IRC) or date of death from any cause, whichever comes first. PD defined as per IMWG criteria as: increase of \>=25% from lowest confirmed value in any one of following criteria: serum M-protein (absolute increase must be \>=0.5 g/dL), serum M-protein increase \>=1 g/dL if lowest M component was \>=5 g/dL; urine M-component (absolute increase must be \>=200 mg/24hour), appearance of new lesion(s), \>=50% increase from nadir in SPD of \>1 lesion, or \>=50% increase in the longest diameter of previous lesion \>1 centimeter (cm) in short axis.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=36 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=25 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Progression Free Survival in High Risk Cytogenetic Population	3.745 months Interval 2.793 to 7.885	7.491 months Interval 2.628 to Due to smaller number of participants with an event, 95% CI could not be calculated.

SECONDARY outcome

Timeframe: From the date of the first IRC determined response to the date of first IRC progression or death, whichever occurred first (maximum duration 76.7 weeks)

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

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

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=54 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=93 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Duration of Response (DOR) as Per Independent Response Committee	11.07 months Interval 8.542 to Due to smaller number of participants with an event, 95% CI could not be calculated.	13.27 months Interval 10.612 to Due to smaller number of participants with an event, 95% CI could not be calculated.

SECONDARY outcome

Timeframe: From the date of randomization to the date of first IRC determined response, or death or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

TT1R was defined as the time from randomization to the date of first IRC determined response (PR or better) that is subsequently confirmed. PR was defined as \>=50% reduction of serum M-protein and reduction in 24 hours urinary M-protein by \>=90% or to \<200 mg/24 h. In addition to the above listed criteria, if present at baseline, a \>=50% reduction in the size (SPD) of soft tissue plasmacytomas was also required.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Time to First Response (TT1R) as Per Independent Response Committee	3.02 months Interval 2.825 to 5.06	1.94 months Interval 1.314 to 2.004

SECONDARY outcome

Timeframe: From the date of randomization to date of first occurrence of IRC determined best overall response or data cut-off whichever comes first (maximum duration 76.7 weeks)

Population: Analysis was performed on ITT population.

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

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=153 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=154 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Time to Best Response (TTBR) as Per Independent Response Committee	5.06 months Interval 3.778 to 7.885	4.30 months Interval 2.891 to 5.125

SECONDARY outcome

Timeframe: Up to 76.7 weeks

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

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

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=2 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=14 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Number of Participants With Minimal Residual Disease (MRD) MRD positive:1 in 10^4	2 Participants	4 Participants
Number of Participants With Minimal Residual Disease (MRD) MRD positive:1 in 10^6	2 Participants	9 Participants
Number of Participants With Minimal Residual Disease (MRD) MRD negative:1 in 10^4	0 Participants	10 Participants
Number of Participants With Minimal Residual Disease (MRD) MRD negative:1 in 10^5	0 Participants	8 Participants
Number of Participants With Minimal Residual Disease (MRD) MRD negative:1 in 10^6	0 Participants	2 Participants
Number of Participants With Minimal Residual Disease (MRD) MRD positive:1 in 10^5	2 Participants	6 Participants

SECONDARY outcome

Timeframe: From randomization up to 30 days after last dose of study drug (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)

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

Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). An SAE is any untoward medical occurrence that at any dose: results in death, is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability/incapacity, is a congenital anomaly/birth defect, is a medically important event.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=149 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=152 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE	146 Participants	151 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any treatment emergent SAE	91 Participants	112 Participants
Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) Any TEAE leading to treatment discontinuation	22 Participants	19 Participants

SECONDARY outcome

Timeframe: End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1

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

CEOI was defined as the plasma concentration at end of infusion.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=149 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) End of infusion: C1D1	163.05 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 34.528	—
Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) End of infusion: C1D15	269.20 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 32.622	—
Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) End of infusion: C2D1	299.85 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 35.921	—
Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) End of infusion: C4D1	279.31 microgram per milliliter (mcg/mL) Geometric Coefficient of Variation 47.555	—

SECONDARY outcome

Timeframe: End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1

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

Accumulation Ratio was defined as the ratio of CEOI of Cycle 2 Day 1 versus Cycle 1 Day 1 and Cycle 4 Day 1 versus Cycle 1 Day 1, where CEOI was the plasma concentration at the end of infusion.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=149 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI) C2D1 versus C1D1	1.860 ratio Geometric Coefficient of Variation 170.9185	—
Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI) C4D1 versus C1D1	1.777 ratio Geometric Coefficient of Variation 224.2542	—

SECONDARY outcome

Timeframe: Cycle 1:1 hour after End of Infusion on Day 1; Cycle 4:1 hour after End of Infusion on Day 1

CEOI+1 hour was defined as the plasma concentration of isatuximab at 1 hour after end of infusion.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=149 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour) C1D1	171.55 mcg/mL Geometric Coefficient of Variation 38.299	—
Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour) C4D1	294.96 mcg/mL Geometric Coefficient of Variation 57.331	—

SECONDARY outcome

Timeframe: Pre-infusion on C1D1, C1D8, C1D15, C1D22, C2D1, C2D15, C3D1, C3D15, C4D1, C4D15, C5D1, C6D1, C7D1, C8D1, C9D1, C10D1, C11D1, C12D1, C13D1, C14D1, C15D1, C16D1, C17D1, C18D1, C19D1, C20D1; End of treatment (EOT [30 days after last drug administration])

Trough Concentration (Ctrough) is the concentration prior to study drug administration.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=149 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
PK Parameter: Plasma Concentration of Isatuximab at Ctrough EOT	9.51 mcg/mL Geometric Coefficient of Variation 136.883	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C1D1	0.00 mcg/mL Geometric Coefficient of Variation 1194.973	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C1D8	31.49 mcg/mL Geometric Coefficient of Variation 53.602	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C1D15	57.89 mcg/mL Geometric Coefficient of Variation 54.764	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C1D22	84.82 mcg/mL Geometric Coefficient of Variation 57.666	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C2D1	89.09 mcg/mL Geometric Coefficient of Variation 60.155	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C2D15	89.35 mcg/mL Geometric Coefficient of Variation 61.167	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C3D1	64.15 mcg/mL Geometric Coefficient of Variation 76.469	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C3D15	91.73 mcg/mL Geometric Coefficient of Variation 78.406	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C4D1	86.05 mcg/mL Geometric Coefficient of Variation 70.062	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C4D15	105.42 mcg/mL Geometric Coefficient of Variation 68.035	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C5D1	106.08 mcg/mL Geometric Coefficient of Variation 65.275	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C6D1	111.33 mcg/mL Geometric Coefficient of Variation 64.985	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C7D1	134.14 mcg/mL Geometric Coefficient of Variation 60.017	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C8D1	146.15 mcg/mL Geometric Coefficient of Variation 55.946	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C9D1	162.84 mcg/mL Geometric Coefficient of Variation 65.193	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C10D1	145.86 mcg/mL Geometric Coefficient of Variation 60.719	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C11D1	169.39 mcg/mL Geometric Coefficient of Variation 56.078	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C12D1	182.32 mcg/mL Geometric Coefficient of Variation 56.814	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C13D1	215.85 mcg/mL Geometric Coefficient of Variation 54.667	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C14D1	214.88 mcg/mL Geometric Coefficient of Variation 55.172	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C15D1	253.61 mcg/mL Geometric Coefficient of Variation 58.885	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C16D1	206.60 mcg/mL Geometric Coefficient of Variation 50.965	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C17D1	242.79 mcg/mL Geometric Coefficient of Variation 45.364	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C18D1	216.70 mcg/mL Geometric Coefficient of Variation 58.273	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C19D1	240.36 mcg/mL Geometric Coefficient of Variation 42.099	—
PK Parameter: Plasma Concentration of Isatuximab at Ctrough C20D1	164.07 mcg/mL	—

SECONDARY outcome

Timeframe: Pre-infusion on Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 4 Day 1

Accumulation Ratio was defined as the ratio of Ctrough of Cycle 2 Day 1 versus Cycle 1 Day 8 and Cycle 4 Day 1 versus Cycle 1 Day 8, where Ctrough is the concentration prior to study drug administration.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=149 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough) C2D1 versus C1D8	2.689 ratio Geometric Coefficient of Variation 734.5547	—
PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough) C4D1 versus C1D8	2.620 ratio Geometric Coefficient of Variation 645.4171	—

SECONDARY outcome

Timeframe: From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)

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

ADA were categorized as: pre-existing, treatment induced and treatment boosted response. Pre-existing ADA was defined as ADA that were present in samples drawn during the pretreatment period (i.e., before the first isatuximab administration). Treatment-induced ADA was defined as ADA that developed at any time during the ADA on-study observation period in participants without preexisting ADA, including participants without pretreatment samples. Treatment boosted ADA was defined as pre-existing ADA that increased at least 2 titer steps between pre-treatment and post-treatment.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=151 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Number of Participants With Anti-drug Antibodies (ADA) Pre-existing ADA	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Treatment induced ADA	0 Participants	—
Number of Participants With Anti-drug Antibodies (ADA) Treatment boosted ADA	0 Participants	—

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

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

EORTC-Quality of Life Questionnaire (QLQ)-C30 is a cancer-specific instrument with 30 questions for evaluation of new chemotherapy and provides an assessment of participant reported outcome dimensions. EORTC QLQ-C30 included GHS/ QOL, functional scales (physical, role, cognitive, emotional, social), symptom scales (fatigue, pain, nausea/vomiting), and 6 single items (dyspnea, appetite loss, insomnia, constipation, diarrhea, financial difficulties). Most questions from QLQ-C30 were a 4-point scale (1/Not at All to 4/Very Much), except Items 29-30, which comprise GHS scale and were a 7-point scale (1/Very Poor to 7/Excellent). Answers were converted into grading scale, with values between 0 and 100. A high score represented a favorable outcome with a best quality of life for participant.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=134 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=139 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score Day 1: Cycle 3	-1.45 score on a scale Standard Deviation 21.03	-1.22 score on a scale Standard Deviation 22.42
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score Baseline	61.19 score on a scale Standard Deviation 20.64	60.10 score on a scale Standard Deviation 20.02
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score Day 1: Cycle 6	-0.12 score on a scale Standard Deviation 22.26	-0.16 score on a scale Standard Deviation 18.28
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score Day 1: Cycle 9	1.06 score on a scale Standard Deviation 19.97	0.41 score on a scale Standard Deviation 20.99
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Cancer Specific Questionnaire With 30 Items (EORTC QLQ-C30): Global Health Status (GHS)/Quality of Life (QOL) Score Day 1: Cycle 17	-9.17 score on a scale Standard Deviation 24.36	-1.92 score on a scale Standard Deviation 19.29

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

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

EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Disease symptoms domain is one of the four domain scores. Disease symptoms domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0 -100 scale, where higher scores = more symptoms and lower health-related quality of life (HRQL) and lower score = less symptoms and more HRQL

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=130 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=137 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score Day 1: Cycle 3	-3.79 score on a scale Standard Deviation 16.09	-2.07 score on a scale Standard Deviation 17.51
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score Day 1: Cycle 9	-2.83 score on a scale Standard Deviation 15.04	-4.66 score on a scale Standard Deviation 13.73
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score Day 1: Cycle 17	-3.33 score on a scale Standard Deviation 15.54	0.00 score on a scale Standard Deviation 21.40
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score Baseline	24.91 score on a scale Standard Deviation 20.67	24.12 score on a scale Standard Deviation 20.54
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Disease Symptoms Domain Score Day 1: Cycle 6	-4.08 score on a scale Standard Deviation 17.95	-3.30 score on a scale Standard Deviation 16.01

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

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

EORTC QLQ-MY20 is a validated questionnaire to assess the overall quality of life in participants with multiple myeloma. Side effects of treatment domain is one of the four domain scores. Side effects of treatment domain score used 4-point scale (1 'Not at All' to 4 'Very Much'). Scores are averaged, and transformed to 0-100 scale, where higher scores = more side effects and lower HRQL and lower scores = less side effects and better HRQL.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=130 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=137 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score Baseline	17.49 score on a scale Standard Deviation 15.25	15.60 score on a scale Standard Deviation 11.63
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score Day 1: Cycle 3	1.69 score on a scale Standard Deviation 11.54	2.61 score on a scale Standard Deviation 13.39
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score Day 1: Cycle 6	-0.13 score on a scale Standard Deviation 15.10	2.11 score on a scale Standard Deviation 11.78
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score Day 1: Cycle 9	1.43 score on a scale Standard Deviation 14.66	3.14 score on a scale Standard Deviation 11.88
Change From Baseline in European Organization for Research and Treatment of Cancer Quality of Life Multiple Myeloma Specific Module With 20 Items (EORTC QLQ-MY20): Side Effects of Treatment Domain Score Day 1: Cycle 17	-2.93 score on a scale Standard Deviation 15.94	3.02 score on a scale Standard Deviation 15.72

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

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

The EQ-5D-5L is a standardized measure of health status that provides a general assessment of health and wellbeing. The EQ-5D descriptive system comprises 5 dimensions: mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each dimension has a 5-level response: no problems, slight problems, moderate problems, severe problems, and extreme problems. Response options are measured with a 5-point Likert scale (for the 5L version). The 5D-5L systems are converted into a single index utility score between 0 to 1, where higher score indicates a better health state and lower score indicate worse health state.

Outcome measures

Outcome measures
Measure	Pd (Pomalidomide + Dexamethasone) n=134 Participants Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	IPd (Isatuximab + Pomalidomide + Dexamethasone) n=140 Participants Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants \>= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value Baseline	0.70 score on a scale Standard Deviation 0.24	0.71 score on a scale Standard Deviation 0.21
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value Day 1: Cycle 3	-0.01 score on a scale Standard Deviation 0.22	-0.01 score on a scale Standard Deviation 0.22
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value Day 1: Cycle 6	0.02 score on a scale Standard Deviation 0.22	-0.00 score on a scale Standard Deviation 0.20
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value Day 1: Cycle 9	-0.03 score on a scale Standard Deviation 0.27	-0.01 score on a scale Standard Deviation 0.15
Change From Baseline in European Quality of Life Working Group Health Status Measure 5 Dimensions (5D), 5 Levels (5L) (EQ-5D-5L) Score: Health State Utility Index Value Day 1: Cycle 17	-0.02 score on a scale Standard Deviation 0.19	-0.01 score on a scale Standard Deviation 0.23

SECONDARY outcome

Timeframe: Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)

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

EQ-5D-5L is a standardized, participant-rated questionnaire to assess health-related quality of life. The EQ-5D-5L includes 2 components: the EQ-5D-5L health state utility index (descriptive system) and the EQ-5D-5L Visual Analog Scale. The Visual Analogue Scale is designed to rate the participant's current health state on a scale from 0 to 100, where 0 represents the worst imaginable health state and 100 represents the best imaginable health state.

Outcome measures

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

Adverse Events

Pd (Pomalidomide + Dexamethasone)

Serious events: 91 serious events

Other events: 139 other events

Deaths: 115 deaths

IPd (Isatuximab + Pomalidomide + Dexamethasone)

Serious events: 112 serious events

Other events: 145 other events

Deaths: 110 deaths

Serious adverse events

Other adverse events

Additional Information

Trial Transparency Team

Sanofi aventis recherche & développement

Phone: 800-633-1610

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee 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.
Publication restrictions are in place

Restriction type: OTHER