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

• Sponsor: Sanofi (Industry)
• Overall Status: Active, not recruiting
• CT.gov ID: NCT02990338
• Collaborator: (none)
• Enrollment: 307
• Locations: 111
• Arms: 2
• Anticipated Duration (Months): 81.2
• Patients Per Site: 2.8
• Patients Per Site Per Month: 0

Study Details

Study Description

Brief Summary

Primary Objective:

To demonstrate the benefit of isatuximab in combination with pomalidomide and low-dose dexamethasone in the prolongation of Progression Free Survival (PFS) as compared to pomalidomide and low-dose dexamethasone in participants with refractory or relapsed and refractory multiple myeloma (MM).

Secondary Objectives:

• To evaluate the Overall Response Rate (ORR) as per International Myeloma Working Group (IMWG) criteria in each arm.

• To compare the Overall Survival (OS) between the two arms.

• To evaluate the Time To Progression (TTP) in each arm.

• To evaluate the PFS in high risk cytogenetic population in each arm.

• To evaluate the Duration of Response (DOR) in each arm.

• To evaluate the safety in both treatment arms.

• To determine the Pharmacokinetic profile of isatuximab in combination with pomalidomide.

• To evaluate the immunogenicity of isatuximab.

• To assess disease-specific and generic health-related quality of life (HRQL), disease and treatment-related symptoms, health state utility, and health status.

Condition or Disease	Intervention/Treatment	Phase
Plasma Cell Myeloma	Drug: Isatuximab; Drug: Pomalidomide; Drug: Dexamethasone	Phase 3

Detailed Description

The duration of the study for the participants included a period for screening of up to 21 days (or up to 28 days for women who can become pregnant). Participants continued study treatment until disease progression, unacceptable adverse reaction, participants' wish or other reason of discontinuation.

During follow-up, participants who discontinued the study treatment due to progression of the disease were followed every 3 months (12 weeks) for survival (or until cut-off date), and participants who discontinued the study treatment prior to documentation of disease progression were followed-up every 4 weeks until disease progression, and then every 3 months (12 weeks) for survival (or until cut-off date).

Study Design

• Study Type: Interventional
• Actual Enrollment: 307 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: A Phase 3 Randomized, Open-label, Multicenter Study Comparing Isatuximab (SAR650984) in Combination With Pomalidomide and Low-Dose Dexamethasone Versus Pomalidomide and Low-Dose Dexamethasone in Patients With Refractory or Relapsed and Refractory Multiple Myeloma
• Actual Study Start Date: Dec 22, 2016
• Actual Primary Completion Date: Nov 22, 2018
• Anticipated Study Completion Date: Sep 29, 2023

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Pd (pomalidomide + dexamethasone) Participants received pomalidomide 4 milligrams (mg) Per os (PO) on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants greater than or equal to (>=) 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).	Drug: Pomalidomide; Pharmaceutical form:capsule Route of administration: oral; Other Names: POMALYST IMNOVID ; Drug: Dexamethasone; Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous
Experimental: IPd (isatuximab + pomalidomide + dexamethasone) Participants received isatuximab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).	Drug: Isatuximab; Pharmaceutical form:solution for infusion Route of administration: intravenous; Other Names: SAR650984 Sarclisa ; Drug: Pomalidomide; Pharmaceutical form:capsule Route of administration: oral; Other Names: POMALYST IMNOVID ; Drug: Dexamethasone; Pharmaceutical form:tablets or solution for infusion Route of administration: oral or intravenous

Outcome Measures

Primary Outcome Measures

1. Progression Free Survival (PFS) [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)]

   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.

Secondary Outcome Measures

1. Overall Response Rate (ORR): Percentage of Participants With Overall Response [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)]

   ORR: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 using IMWG criteria. 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.

2. Overall Survival (OS) [From the date of randomization to date of death from any cause or study cut-off date, whichever was earlier (maximum duration 76.7 weeks)]

   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.

3. Time to Progression (TTP) [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)]

   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.

4. Progression Free Survival in High Risk Cytogenetic Population [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)]

   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.

5. Duration of Response (DOR) [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)]

   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.

6. Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs) [From randomization up to 30 days after last dose of study drug (maximum duration 76.7 weeks)]

   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.

7. Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI) [End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1]

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

8. Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI) [End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1]

   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.

9. Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour) [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.

10. PK Parameter: Plasma Concentration of Isatuximab at Ctrough [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.

11. PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough) [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.

12. Number of Participants With Anti-drug Antibodies (ADA) [From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)]

    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.

13. 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, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

    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.

14. 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, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

    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

15. 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, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

    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.

16. 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, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

    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.

17. 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, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)]

    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.

18. Percentage of Participants With Best Overall Response (BOR) [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)]

    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.

19. Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit [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)]

    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.

20. Percentage of Participants With Very Good Partial Response (VGPR) [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)]

    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 (CR), 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.

21. Time to First Response (TT1R) [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)]

    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.

22. Time to Best Response (TTBR) [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)]

    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.

23. Number of Participants With Minimal Residual Disease (MRD) [Up to 76.7 weeks]

    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.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion criteria :

• Age superior or equal to 18 years or country's legal age of majority if the legal age was superior to 18 years old.

• Participants had a documented diagnosis of multiple myeloma with evidence of measurable disease i.e. serum M protein superior or equal to 0.5 grams per decilitre (g/dL) measured using serum protein immunoelectrophoresis and or urine M protein superior or equal to 200 mg per 24 hours measured using urine protein immunoelectrophoresis.

• Participants had received at least 2 prior lines of anti-myeloma therapy, which must include at least 2 consecutive cycles of lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib or ixazomib) given alone or in combination.

• Participants had failed treatment with lenalidomide and a proteasome inhibitor (bortezomib, carfilzomib, or ixazomib) alone or in combination (Intolerant, progression within 6 months after reaching Partial Response or better).

• Participants had progressed on or within 60 days after end of previous therapy before to study entry, i.e., refractory to the last line of treatment.

Exclusion criteria:

• Primary refractory multiple myeloma defined as participants who had never achieved at least a minimal response (MR) with any treatment during the disease course.

• Free Light Chain measurable disease only.

• Prior therapy with pomalidomide.

• Any anti-myeloma drug treatment within 14 days before randomization, including dexamethasone.

• Eastern Cooperative Oncology Group performance status superior to 2.

• Platelets inferior to 75 000 cells per microliter (mcL) if inferior to 50% of bone marrow (BM) nucleated cells are plasma cells, and inferior to 30 000 cells per mcL if superior or equal to 50% of BM nucleated cells are plasma cells. Platelet transfusion was not allowed within three days before the screening visit.

• Absolute neutrophil count inferior to 1000 per mcL (1 x 10^9/L).

• Creatinine clearance inferior to 30 mL per minute (Modification of Diet in Renal Disease [MDRD] Formula).

• Total bilirubin superior to 2 x ULN (Upper Limit of Normal).

• Corrected serum calcium superior to 14 milligrams per deciliter (mg/dL) (superior to 3.5 millimoles per liter (mmol/L).

• Aspartate aminotransferase (AST) and/or Alanine Aminotransferase (ALT) superior to 3 x ULN.

• Hypersensitivity to immunomodulatory drugs (IMiDs) (thalidomide or lenalidomide) defined as any hypersensitivity reaction leading to stop IMiDs within the 2 first cycles or toxicity, which does meet intolerance definition.

• Hypersensitivity to dexamethasone, sucrose histidine (as base and hydrochloride salt), and polysorbate 80 or any of the components of study therapy that are not amenable to premedication with steroids, or H2 blockers that would prohibit further treatment with these agents.

• Significant cardiac dysfunction; myocardial infarction within 12 months; unstable, poorly controlled angina pectoris.

• Pregnant or breastfeeding woman or female who intends to become pregnant during the participation in the study.

• Male participants who disagreed to practice true abstinence or disagreed to use a condom during sexual contact with a pregnant female or a female of childbearing potential while participating in the study, during dose interruptions and at least 3 or 5 months following study treatment discontinuation, even if he had undergone a successful vasectomy.

• All participants who disagreed to refrain from donating blood while on study treatment and for 4 weeks after discontinuation from this study treatment.

The above information was not intended to contain all considerations relevant to a participant's potential participation in a clinical trial.

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Investigational Site Number :8400002	Plantation	Florida	United States	33324
2	Investigational Site Number :8400006	Boston	Massachusetts	United States	02215
3	Investigational Site Number :0360004	St Leonards	New South Wales	Australia	2065
4	Investigational Site Number :0360001	Waratah	New South Wales	Australia	2298
5	Investigational Site Number :0360005	Melbourne	Victoria	Australia	3000
6	Investigational Site Number :0360002	Melbourne	Victoria	Australia	3004
7	Investigational Site Number :0360006	Richmond	Victoria	Australia	3121
8	Investigational Site Number :0560003	Antwerpen		Belgium	2060
9	Investigational Site Number :0560002	Brussel		Belgium	1090
10	Investigational Site Number :0560004	Gent		Belgium	9000
11	Investigational Site Number :0560001	Leuven		Belgium	3000
12	Investigational Site Number :1240001	Montreal	Quebec	Canada	H1T 2M4
13	Investigational Site Number :1240004	Montreal	Quebec	Canada	H4A 3J1
14	Investigational Site Number :1240005	Sherbrooke	Quebec	Canada	J1H 5N4
15	Investigational Site Number :2030005	Brno		Czechia	62500
16	Investigational Site Number :2030004	Hradec Kralove		Czechia	50005
17	Investigational Site Number :2030001	Olomouc		Czechia	77900
18	Investigational Site Number :2030002	Ostrava - Poruba		Czechia	70852
19	Investigational Site Number :2030003	Praha 2		Czechia	12808
20	Investigational Site Number :2080002	Ålborg		Denmark	9100
21	Investigational Site Number :2500021	Bayonne		France	64100
22	Investigational Site Number :2500008	Caen		France	14033
23	Investigational Site Number :2500009	Dijon		France	21000
24	Investigational Site Number :2500017	Grenoble		France	38043
25	Investigational Site Number :2500013	La Roche Sur Yon		France	85925
26	Investigational Site Number :2500003	Lille		France	59037
27	Investigational Site Number :2500023	Limoges		France	87042
28	Investigational Site Number :2500019	Montpellier Cedex		France	34295
29	Investigational Site Number :2500002	Nantes		France	44093
30	Investigational Site Number :2500015	Paris		France	75005
31	Investigational Site Number :2500016	Paris		France	75743
32	Investigational Site Number :2500005	Pessac		France	33600
33	Investigational Site Number :2500004	Pierre Benite		France	69495
34	Investigational Site Number :2500007	POITIERS Cedex		France	86021
35	Investigational Site Number :2500025	Reims		France	51092
36	Investigational Site Number :2500014	Rennes		France	35033
37	Investigational Site Number :2500001	TOULOUSE Cedex 9		France	31059
38	Investigational Site Number :2500012	Tours		France	37044
39	Investigational Site Number :2500018	Vandoeuvre-les-nancy		France	54511
40	Investigational Site Number :2760001	Leipzig		Germany	04103
41	Investigational Site Number :3000002	Athens		Greece	106 76
42	Investigational Site Number :3000005	Athens		Greece	11527
43	Investigational Site Number :3000001	Athens		Greece	11528
44	Investigational Site Number :3000004	Patra		Greece	26504
45	Investigational Site Number :3000003	Thessaloniki		Greece	57010
46	Investigational Site Number :3480001	Budapest		Hungary	1083
47	Investigational Site Number :3480003	Budapest		Hungary	1097
48	Investigational Site Number :3480002	Debrecen		Hungary	4032
49	Investigational Site Number :3800001	Bologna		Italy	40138
50	Investigational Site Number :3800010	Catania		Italy	95123
51	Investigational Site Number :3800009	Firenze		Italy	50134
52	Investigational Site Number :3800008	Genova		Italy	16132
53	Investigational Site Number :3800007	Milano		Italy	20132
54	Investigational Site Number :3800002	Milano		Italy	20133
55	Investigational Site Number :3800006	Padova		Italy	35128
56	Investigational Site Number :3800004	Terni		Italy	05100
57	Investigational Site Number :3800003	Torino		Italy	10126
58	Investigational Site Number :3920001	Nagoya-shi	Aichi	Japan	467-8602
59	Investigational Site Number :3920005	Shibukawa-shi	Gunma	Japan	377-0280
60	Investigational Site Number :3920004	Sapporo-shi	Hokkaido	Japan	060-8543
61	Investigational Site Number :3920006	Kyoto-shi	Kyoto	Japan	603-8151
62	Investigational Site Number :3920008	Suwa-shi	Nagano	Japan	392-8510
63	Investigational Site Number :3920003	Okayama-shi	Okayama	Japan	701-1192
64	Investigational Site Number :3920007	Sunto-gun	Shizuoka	Japan	411-8777
65	Investigational Site Number :3920002	Shibuya-ku	Tokyo	Japan	150-8935
66	Investigational Site Number :4100007	Hwasun-gun	Jeollanam-do	Korea, Republic of	58128
67	Investigational Site Number :4100001	Seoul	Seoul-teukbyeolsi	Korea, Republic of	03080
68	Investigational Site Number :4100002	Seoul	Seoul-teukbyeolsi	Korea, Republic of	06351
69	Investigational Site Number :4100006	Incheon		Korea, Republic of	21565
70	Investigational Site Number :4100005	Seoul		Korea, Republic of	06591
71	Investigational Site Number :5540001	Takapuna	Auckland	New Zealand	1309
72	Investigational Site Number :5540004	Dunedin	Otago	New Zealand	9016
73	Investigational Site Number :5540003	Hamilton	Waikato	New Zealand	3204
74	Investigational Site Number :5540002	Auckland		New Zealand	2025
75	Investigational Site Number :5780001	Oslo		Norway	0450
76	Investigational Site Number :6160003	Lublin	Lubuskie	Poland	20-081
77	Investigational Site Number :6160005	Krakow	Malopolskie	Poland	31-501
78	Investigational Site Number :6160001	Warszawa	Mazowieckie	Poland	02-776
79	Investigational Site Number :6160002	Chorzow	Slaskie	Poland	41-500
80	Investigational Site Number :6200004	Coimbra		Portugal	3000-075
81	Investigational Site Number :6200002	Lisboa		Portugal	1070
82	Investigational Site Number :6200001	Porto		Portugal	4200
83	Investigational Site Number :6430004	Moscow		Russian Federation	125167
84	Investigational Site Number :6430001	Moscow		Russian Federation	125284
85	Investigational Site Number :6430002	Moscow		Russian Federation	129301
86	Investigational Site Number :7030001	Bratislava		Slovakia	83310
87	Investigational Site Number :7240005	Santiago de Compostela	A Coruña [La Coruña]	Spain	15706
88	Investigational Site Number :7240001	Barcelona	Barcelona [Barcelona]	Spain	08035
89	Investigational Site Number :7240006	Santander	Cantabria	Spain	39008
90	Investigational Site Number :7240002	Pamplona	Navarra	Spain	31008
91	Investigational Site Number :7240003	Madrid		Spain	28006
92	Investigational Site Number :7240004	Salamanca		Spain	37007
93	Investigational Site Number :7520004	Luleå		Sweden	97180
94	Investigational Site Number :7520005	Uddevalla		Sweden	451 80
95	Investigational Site Number :1580004	Kaohsiung		Taiwan	833
96	Investigational Site Number :1580002	Taichung		Taiwan	40447
97	Investigational Site Number :1580001	Taipei		Taiwan	100
98	Investigational Site Number :1580003	Taoyuan		Taiwan	333
99	Investigational Site Number :7920001	Ankara		Turkey
100	Investigational Site Number :7920002	Antalya		Turkey
101	Investigational Site Number :7920005	Istanbul		Turkey	34010
102	Investigational Site Number :7920006	Istanbul		Turkey	34381
103	Investigational Site Number :7920003	Istanbul		Turkey	34390
104	Investigational Site Number :7920004	Istanbul		Turkey
105	Investigational Site Number :7920008	Izmir		Turkey	35040
106	Investigational Site Number :7920010	Izmir		Turkey	35340
107	Investigational Site Number :7920009	Kayseri		Turkey	38039
108	Investigational Site Number :7920007	Kocaeli		Turkey	41400
109	Investigational Site Number :8260002	London	London, City Of	United Kingdom	EC1A 7BE
110	Investigational Site Number :8260003	London	London, City Of	United Kingdom	SE1 9RT
111	Investigational Site Number :8260001	London	London, City Of	United Kingdom	WC1E6AG

Sponsors and Collaborators

• Sanofi

Investigators

• Study Director: Clinical Sciences & Operations, Sanofi

Study Documents (Full-Text)

• Study Protocol - Jun 11, 2019
• Statistical Analysis Plan - Nov 7, 2018

More Information

Publications

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

• Responsible Party: Sanofi
• ClinicalTrials.gov Identifier: NCT02990338
• Other Study ID Numbers: EFC14335; 2016-003097-41; U1111-1180-6262
• First Posted: Dec 13, 2016
• Last Update Posted: Apr 19, 2022
• Last Verified: Mar 16, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Keywords provided by Sanofi: Anti-CD38 monoclonal antibody
• Additional relevant MeSH terms: Multiple Myeloma; Neoplasms, Plasma Cell; Dexamethasone; Pomalidomide

Study Results

Participant Flow

Recruitment Details	The study was conducted at 102 sites in 24 countries. A total of 387 participants were screened between 22 December 2016 and 01 February 2018. Out of which, 307 participants were randomized in 1:1 ratio to IPd (Isatuximab + Pomalidomide + Dexamethasone) and Pd (Pomalidomide + Dexamethasone) arms using an interactive response technology (IRT).
Pre-assignment Detail	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). Results are reported based on the primary completion date of 22 November 2018.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 milligrams (mg) Per os (PO) on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 milligrams per kilogram (mg/kg) intravenous (IV) infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Period Title: Overall Study
STARTED	153	154
Treated	149	152
Ongoing	35	65
COMPLETED	35	65
NOT COMPLETED	118	89

Baseline Characteristics

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)	Total
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).	Total of all reporting groups
Overall Participants	153	154	307
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	65.2 (9.5)	66.6 (9.1)	65.9 (9.3)
Sex: Female, Male (Count of Participants)
Female	83 54.2%	65 42.2%	148 48.2%
Male	70 45.8%	89 57.8%	159 51.8%
Race (NIH/OMB) (Count of Participants)
American Indian or Alaska Native	0 0%	0 0%	0 0%
Asian	15 9.8%	21 13.6%	36 11.7%
Native Hawaiian or Other Pacific Islander	1 0.7%	2 1.3%	3 1%
Black or African American	3 2%	1 0.6%	4 1.3%
White	126 82.4%	118 76.6%	244 79.5%
More than one race	0 0%	0 0%	0 0%
Unknown or Not Reported	8 5.2%	12 7.8%	20 6.5%

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pd (Pomalidomide + Dexamethasone), IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Comments	Confidence interval (CI) for Kaplan-Meier estimates were calculated with log-log transformation of survival function and methods of Brookmeyer and Crowley.
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the type I error rate meaning no further testing would be performed unless the significance level had been reached on PFS.
Statistical Test of Hypothesis	p-Value	0.0010
	Comments	One-sided p-value based on Stratified log-rank test. Threshold for statistical significance at 0.025.
	Method	Log Rank
	Comments	Stratification was based on age (<75 years versus >=75 years) and number of previous lines of therapy (2 or 3 versus >3) according to IRT.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.596
	Confidence Interval	(2-Sided) 95%; 0.436 to 0.814
	Parameter Dispersion	Type: Value:
	Estimation Comments

2. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Measure Participants	153	154
Number [percentage of participants]	35.3 23.1%	60.4 39.2%

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pd (Pomalidomide + Dexamethasone), IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Comments
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the type I error rate meaning no further testing would be performed unless the significance level had been reached on PFS.
Statistical Test of Hypothesis	p-Value	<0.0001
	Comments	Threshold for statistical significance at 0.025.
	Method	Cochran-Mantel-Haenszel
	Comments	One sided p-value was stratified based on age (<75 years versus >=75 years) and number of previous lines (2 or 3 versus >3) according to IRT.

3. Secondary Outcome

Title	Overall Survival (OS)
Description	OS was defined as the time from the date of randomization to death from any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive or at the cut-off date, whichever comes first.
Time Frame	From the date of randomization to date of death from any cause or study cut-off date, whichever was earlier (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

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

Statistical Analysis 1

Statistical Analysis Overview	Comparison Group Selection	Pd (Pomalidomide + Dexamethasone), IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Comments	CI for Kaplan-Meier estimates are calculated with log-log transformation of survival function and methods of Brookmeyer and Crowley.
	Type of Statistical Test	Superiority
	Comments	A closed test procedure was used to control the type I error rate meaning no further testing would be performed unless the significance level had been reached on PFS.
Statistical Test of Hypothesis	p-Value	0.0631
	Comments	One-sided significance level was 0.0008 using the O'Brien-Fleming alpha spending function.
	Method	Log Rank
	Comments	Stratified on age (<75 years versus >=75 years) and number of previous lines of therapy (2 or 3 versus > 3) according to IRT.
Method of Estimation	Estimation Parameter	Hazard Ratio (HR)
	Estimated Value	0.687
	Confidence Interval	(2-Sided) 95%; 0.461 to 1.023
	Parameter Dispersion	Type: Value:
	Estimation Comments

4. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

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

5. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

6. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

7. Secondary Outcome

Title	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)
Description	Adverse Event (AE) was defined as any untoward medical occurrence in a participant who received study drug and did not necessarily had a causal relationship with the treatment. TEAEs were defined as AEs that developed, worsened (according to the Investigator opinion), or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). An SAE is any untoward medical occurrence that at any dose: results in death, Is life-threatening, requires inpatient hospitalization or prolongation of existing hospitalization, results in persistent or significant disability / incapacity, is a congenital anomaly / birth defect, is a medically important event.
Time Frame	From randomization up to 30 days after last dose of study drug (maximum duration 76.7 weeks)

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Measure Participants	149	152
Any TEAE	146 95.4%	151 98.1%
Any treatment emergent SAE	80 52.3%	94 61%
Any TEAE leading to treatment discontinuation	19 12.4%	11 7.1%

8. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on PK population which included participants who received at least 1 dose of Isatuximab, with data for at least 1 PK parameter available. Here, 'Number analyzed' = participants with available data for each specified category.

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

9. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

10. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

11. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

12. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

13. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ADA evaluable population which included participants who received at least one dose of study drug from the IPd arm with at least one ADA assessment during the ADA on-study observation period with a reportable result.

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

14. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

15. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

16. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

17. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

18. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

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

19. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Measure Participants	153	154
Stringent complete response	0.7 0.5%	0 0%
Complete response	1.3 0.8%	4.5 2.9%
Very good partial response	6.5 4.2%	27.3 17.7%
Partial response	26.8 17.5%	28.6 18.6%
Minimal response	11.1 7.3%	6.5 4.2%
Stable disease	29.4 19.2%	21.4 13.9%
Progressive Disease	9.2 6%	3.9 2.5%
Not evaluable	10.5 6.9%	4.5 2.9%

20. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Measure Participants	153	154
Number [percentage of participants]	46.4 30.3%	66.9 43.4%

21. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Measure Participants	153	154
Number [percentage of participants]	8.5 5.6%	31.8 20.6%

22. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

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

23. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

Analysis was performed on ITT population.

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

24. Secondary Outcome

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

Outcome Measure Data

Analysis Population Description

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

Arm/Group Title	Pd (Pomalidomide + Dexamethasone)	IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).	Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
Measure Participants	2	14
MRD negative:1 in 10^4	0 0%	10 6.5%
MRD negative:1 in 10^5	0 0%	8 5.2%
MRD negative:1 in 10^6	0 0%	2 1.3%
MRD positive:1 in 10^4	2 1.3%	4 2.6%
MRD positive:1 in 10^5	2 1.3%	6 3.9%
MRD positive:1 in 10^6	2 1.3%	9 5.8%

Adverse Events

Time Frame	AE data was collected from the time of signed informed consent to 30 days following the last administration of study treatment (up to 76.7 weeks).
Adverse Event Reporting Description	Reported AEs and deaths are TEAEs that developed, worsened, or became serious during the treatment period (time from the first dose of study treatments up to 30 days after last dose of study treatments). Analysis was performed on safety population.
Arm/Group Title	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
Arm/Group Description	Participants received pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle plus dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone) PO on Days 1, 8, 15 and 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 73.7 weeks).		Participants received isatuximab 10 mg/kg IV infusion on Days 1, 8, 15, and 22 at Cycle 1, and then on Days 1 and 15 of subsequent cycles plus pomalidomide 4 mg PO on Days 1 to 21 of each 28-day treatment cycle and dexamethasone 40 mg (participants >= 75 years of age received 20 mg dexamethasone), PO or IV on Day 1, 8, 15, 22 of each 28-day treatment cycle until disease progression or unacceptable toxicity or participant's wish to discontinue study treatment, or any other reason, whichever comes first (maximum exposure: 76.7 weeks).
All Cause Mortality
	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	13/149 (8.7%)		11/152 (7.2%)
Serious Adverse Events
	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	80/149 (53.7%)		94/152 (61.8%)
Blood and lymphatic system disorders
Anaemia	1/149 (0.7%)	1	3/152 (2%)	4
Febrile Neutropenia	3/149 (2%)	3	10/152 (6.6%)	11
Hyperviscosity Syndrome	2/149 (1.3%)	2	0/152 (0%)	0
Neutropenia	2/149 (1.3%)	2	5/152 (3.3%)	5
Pancytopenia	1/149 (0.7%)	1	1/152 (0.7%)	1
Thrombocytopenia	1/149 (0.7%)	1	3/152 (2%)	3
Cardiac disorders
Acute Coronary Syndrome	0/149 (0%)	0	1/152 (0.7%)	1
Angina Pectoris	1/149 (0.7%)	1	0/152 (0%)	0
Angina Unstable	0/149 (0%)	0	1/152 (0.7%)	1
Arrhythmia Supraventricular	0/149 (0%)	0	1/152 (0.7%)	1
Atrial Fibrillation	1/149 (0.7%)	1	3/152 (2%)	4
Cardiac Failure	1/149 (0.7%)	1	0/152 (0%)	0
Eye disorders
Retinal Detachment	1/149 (0.7%)	1	0/152 (0%)	0
Gastrointestinal disorders
Colitis Ischaemic	0/149 (0%)	0	1/152 (0.7%)	1
Diarrhoea	1/149 (0.7%)	1	1/152 (0.7%)	1
Diverticular Perforation	0/149 (0%)	0	2/152 (1.3%)	3
Oesophagitis	0/149 (0%)	0	1/152 (0.7%)	1
Pancreatitis Acute	1/149 (0.7%)	1	0/152 (0%)	0
General disorders
Asthenia	0/149 (0%)	0	1/152 (0.7%)	1
Death	1/149 (0.7%)	1	2/152 (1.3%)	2
Disease Progression	7/149 (4.7%)	7	7/152 (4.6%)	7
General Physical Health Deterioration	2/149 (1.3%)	2	1/152 (0.7%)	1
Multiple Organ Dysfunction Syndrome	0/149 (0%)	0	1/152 (0.7%)	1
Peripheral Swelling	0/149 (0%)	0	1/152 (0.7%)	1
Pyrexia	2/149 (1.3%)	2	3/152 (2%)	3
Sudden Death	1/149 (0.7%)	1	0/152 (0%)	0
Hepatobiliary disorders
Cholecystitis	0/149 (0%)	0	1/152 (0.7%)	1
Hepatic Failure	0/149 (0%)	0	1/152 (0.7%)	1
Infections and infestations
Acarodermatitis	0/149 (0%)	0	1/152 (0.7%)	1
Atypical Pneumonia	0/149 (0%)	0	2/152 (1.3%)	2
Bronchiolitis	0/149 (0%)	0	2/152 (1.3%)	2
Bronchitis	1/149 (0.7%)	1	3/152 (2%)	3
Candida Pneumonia	1/149 (0.7%)	1	0/152 (0%)	0
Cytomegalovirus Gastrointestinal Infection	1/149 (0.7%)	1	0/152 (0%)	0
Device Related Sepsis	0/149 (0%)	0	1/152 (0.7%)	1
Diverticulitis	1/149 (0.7%)	1	2/152 (1.3%)	2
Escherichia Sepsis	1/149 (0.7%)	1	0/152 (0%)	0
Gastroenteritis	1/149 (0.7%)	1	0/152 (0%)	0
Gastroenteritis Enteroviral	0/149 (0%)	0	1/152 (0.7%)	1
Haemophilus Infection	0/149 (0%)	0	1/152 (0.7%)	1
Herpes Zoster Disseminated	0/149 (0%)	0	1/152 (0.7%)	1
Infection	1/149 (0.7%)	1	0/152 (0%)	0
Influenza	2/149 (1.3%)	2	3/152 (2%)	3
Laryngitis	0/149 (0%)	0	1/152 (0.7%)	1
Lower Respiratory Tract Infection	3/149 (2%)	3	4/152 (2.6%)	4
Lung Infection	3/149 (2%)	3	3/152 (2%)	3
Lymphangitis	0/149 (0%)	0	1/152 (0.7%)	1
Medical Device Site Infection	0/149 (0%)	0	1/152 (0.7%)	1
Orchitis	0/149 (0%)	0	1/152 (0.7%)	1
Pneumocystis Jirovecii Pneumonia	4/149 (2.7%)	4	3/152 (2%)	3
Pneumonia	23/149 (15.4%)	23	23/152 (15.1%)	27
Pneumonia Bacterial	0/149 (0%)	0	2/152 (1.3%)	3
Pneumonia Fungal	0/149 (0%)	0	1/152 (0.7%)	1
Pneumonia Haemophilus	0/149 (0%)	0	2/152 (1.3%)	2
Pneumonia Influenzal	2/149 (1.3%)	2	2/152 (1.3%)	2
Pneumonia Pneumococcal	0/149 (0%)	0	1/152 (0.7%)	1
Pneumonia Streptococcal	1/149 (0.7%)	1	0/152 (0%)	0
Pneumonia Viral	0/149 (0%)	0	3/152 (2%)	3
Postoperative Wound Infection	0/149 (0%)	0	1/152 (0.7%)	1
Pseudomonal Bacteraemia	0/149 (0%)	0	1/152 (0.7%)	1
Pseudomonas Infection	0/149 (0%)	0	1/152 (0.7%)	1
Pyelonephritis	1/149 (0.7%)	1	0/152 (0%)	0
Pyelonephritis Acute	1/149 (0.7%)	1	0/152 (0%)	0
Respiratory Tract Infection	2/149 (1.3%)	2	2/152 (1.3%)	2
Respiratory Tract Infection Viral	0/149 (0%)	0	1/152 (0.7%)	1
Sepsis	2/149 (1.3%)	2	4/152 (2.6%)	4
Septic Shock	3/149 (2%)	3	1/152 (0.7%)	1
Sinusitis	1/149 (0.7%)	1	0/152 (0%)	0
Skin Infection	0/149 (0%)	0	1/152 (0.7%)	1
Soft Tissue Infection	0/149 (0%)	0	1/152 (0.7%)	1
Staphylococcal Bacteraemia	0/149 (0%)	0	1/152 (0.7%)	1
Upper Respiratory Tract Infection	2/149 (1.3%)	2	2/152 (1.3%)	2
Urinary Tract Infection	2/149 (1.3%)	2	6/152 (3.9%)	6
Varicella	0/149 (0%)	0	1/152 (0.7%)	1
Injury, poisoning and procedural complications
Accidental Overdose	1/149 (0.7%)	1	0/152 (0%)	0
Fall	0/149 (0%)	0	1/152 (0.7%)	1
Head Injury	0/149 (0%)	0	1/152 (0.7%)	1
Infusion Related Reaction	1/149 (0.7%)	1	6/152 (3.9%)	6
Traumatic Fracture	0/149 (0%)	0	3/152 (2%)	3
Wound Complication	0/149 (0%)	0	1/152 (0.7%)	1
Investigations
Alanine Aminotransferase Increased	0/149 (0%)	0	1/152 (0.7%)	1
Hepatic Enzyme Increased	0/149 (0%)	0	1/152 (0.7%)	1
Metabolism and nutrition disorders
Decreased Appetite	0/149 (0%)	0	1/152 (0.7%)	1
Dehydration	1/149 (0.7%)	1	1/152 (0.7%)	1
Hypercalcaemia	3/149 (2%)	4	2/152 (1.3%)	2
Hyperglycaemia	0/149 (0%)	0	3/152 (2%)	4
Hyponatraemia	1/149 (0.7%)	1	0/152 (0%)	0
Malnutrition	1/149 (0.7%)	1	0/152 (0%)	0
Tumour Lysis Syndrome	0/149 (0%)	0	1/152 (0.7%)	1
Musculoskeletal and connective tissue disorders
Arthralgia	2/149 (1.3%)	2	4/152 (2.6%)	4
Back Pain	1/149 (0.7%)	1	2/152 (1.3%)	2
Bone Pain	0/149 (0%)	0	2/152 (1.3%)	2
Muscular Weakness	0/149 (0%)	0	1/152 (0.7%)	1
Osteoporotic Fracture	0/149 (0%)	0	1/152 (0.7%)	1
Pathological Fracture	3/149 (2%)	3	5/152 (3.3%)	5
Neoplasms benign, malignant and unspecified (incl cysts and polyps)
Myelodysplastic Syndrome	0/149 (0%)	0	1/152 (0.7%)	1
Squamous Cell Carcinoma Of Skin	0/149 (0%)	0	3/152 (2%)	4
Tumour Associated Fever	1/149 (0.7%)	1	0/152 (0%)	0
Nervous system disorders
Ataxia	1/149 (0.7%)	1	0/152 (0%)	0
Cauda Equina Syndrome	1/149 (0.7%)	1	0/152 (0%)	0
Cerebral Haemorrhage	1/149 (0.7%)	1	0/152 (0%)	0
Haemorrhage Intracranial	1/149 (0.7%)	1	0/152 (0%)	0
Intracranial Aneurysm	0/149 (0%)	0	1/152 (0.7%)	1
Ischaemic Stroke	1/149 (0.7%)	1	0/152 (0%)	0
Presyncope	1/149 (0.7%)	1	0/152 (0%)	0
Spinal Subdural Haematoma	1/149 (0.7%)	1	0/152 (0%)	0
Syncope	1/149 (0.7%)	1	4/152 (2.6%)	4
Transient Ischaemic Attack	0/149 (0%)	0	1/152 (0.7%)	1
Vith Nerve Paresis	0/149 (0%)	0	1/152 (0.7%)	1
Vocal Cord Paralysis	0/149 (0%)	0	1/152 (0.7%)	1
Psychiatric disorders
Acute Psychosis	0/149 (0%)	0	1/152 (0.7%)	1
Confusional State	1/149 (0.7%)	1	1/152 (0.7%)	1
Renal and urinary disorders
Acute Kidney Injury	6/149 (4%)	8	5/152 (3.3%)	5
Hydronephrosis	0/149 (0%)	0	1/152 (0.7%)	1
Renal Aneurysm	1/149 (0.7%)	1	0/152 (0%)	0
Renal Failure	3/149 (2%)	4	1/152 (0.7%)	1
Renal Impairment	0/149 (0%)	0	2/152 (1.3%)	2
Reproductive system and breast disorders
Pelvic Pain	0/149 (0%)	0	2/152 (1.3%)	2
Respiratory, thoracic and mediastinal disorders
Bronchopneumopathy	0/149 (0%)	0	1/152 (0.7%)	1
Chronic Obstructive Pulmonary Disease	0/149 (0%)	0	1/152 (0.7%)	1
Cough	1/149 (0.7%)	1	0/152 (0%)	0
Dyspnoea	2/149 (1.3%)	2	4/152 (2.6%)	4
Haemothorax	0/149 (0%)	0	1/152 (0.7%)	1
Hiccups	0/149 (0%)	0	1/152 (0.7%)	2
Hypoxia	0/149 (0%)	0	1/152 (0.7%)	1
Pleural Effusion	1/149 (0.7%)	1	1/152 (0.7%)	1
Pulmonary Embolism	2/149 (1.3%)	2	3/152 (2%)	3
Pulmonary Oedema	1/149 (0.7%)	1	0/152 (0%)	0
Respiratory Failure	1/149 (0.7%)	1	0/152 (0%)	0
Skin and subcutaneous tissue disorders
Decubitus Ulcer	0/149 (0%)	0	1/152 (0.7%)	1
Vascular disorders
Arteriosclerosis	0/149 (0%)	0	1/152 (0.7%)	1
Deep Vein Thrombosis	1/149 (0.7%)	1	0/152 (0%)	0
Hypertension	1/149 (0.7%)	1	0/152 (0%)	0
Hypotension	0/149 (0%)	0	1/152 (0.7%)	1
Orthostatic Hypotension	1/149 (0.7%)	1	0/152 (0%)	0
Other (Not Including Serious) Adverse Events
	Pd (Pomalidomide + Dexamethasone)		IPd (Isatuximab + Pomalidomide + Dexamethasone)
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	137/149 (91.9%)		142/152 (93.4%)
Blood and lymphatic system disorders
Febrile Neutropenia	0/149 (0%)	0	8/152 (5.3%)	10
Neutropenia	48/149 (32.2%)	76	69/152 (45.4%)	118
Thrombocytopenia	17/149 (11.4%)	18	16/152 (10.5%)	24
Gastrointestinal disorders
Constipation	26/149 (17.4%)	31	24/152 (15.8%)	27
Diarrhoea	28/149 (18.8%)	37	38/152 (25%)	58
Nausea	14/149 (9.4%)	14	23/152 (15.1%)	26
Stomatitis	4/149 (2.7%)	4	10/152 (6.6%)	11
Vomiting	5/149 (3.4%)	5	18/152 (11.8%)	20
General disorders
Asthenia	27/149 (18.1%)	32	22/152 (14.5%)	29
Fatigue	32/149 (21.5%)	33	26/152 (17.1%)	31
Oedema Peripheral	16/149 (10.7%)	19	20/152 (13.2%)	23
Pyrexia	19/149 (12.8%)	21	19/152 (12.5%)	21
Infections and infestations
Bronchitis	12/149 (8.1%)	13	34/152 (22.4%)	51
Nasopharyngitis	7/149 (4.7%)	9	14/152 (9.2%)	19
Pneumonia	5/149 (3.4%)	5	14/152 (9.2%)	14
Upper Respiratory Tract Infection	25/149 (16.8%)	33	41/152 (27%)	66
Urinary Tract Infection	13/149 (8.7%)	15	11/152 (7.2%)	12
Injury, poisoning and procedural complications
Fall	8/149 (5.4%)	10	7/152 (4.6%)	7
Infusion Related Reaction	1/149 (0.7%)	1	51/152 (33.6%)	55
Investigations
Weight Decreased	2/149 (1.3%)	3	10/152 (6.6%)	10
Metabolism and nutrition disorders
Decreased Appetite	7/149 (4.7%)	7	14/152 (9.2%)	18
Musculoskeletal and connective tissue disorders
Arthralgia	11/149 (7.4%)	11	13/152 (8.6%)	14
Back Pain	21/149 (14.1%)	22	24/152 (15.8%)	26
Bone Pain	8/149 (5.4%)	9	10/152 (6.6%)	10
Muscle Spasms	15/149 (10.1%)	17	14/152 (9.2%)	14
Muscular Weakness	7/149 (4.7%)	7	10/152 (6.6%)	10
Musculoskeletal Chest Pain	7/149 (4.7%)	7	13/152 (8.6%)	13
Myalgia	5/149 (3.4%)	5	10/152 (6.6%)	11
Nervous system disorders
Dizziness	4/149 (2.7%)	4	8/152 (5.3%)	9
Headache	8/149 (5.4%)	8	15/152 (9.9%)	16
Peripheral Sensory Neuropathy	9/149 (6%)	9	11/152 (7.2%)	12
Tremor	6/149 (4%)	6	12/152 (7.9%)	13
Psychiatric disorders
Insomnia	12/149 (8.1%)	14	13/152 (8.6%)	14
Respiratory, thoracic and mediastinal disorders
Cough	10/149 (6.7%)	13	14/152 (9.2%)	20
Dyspnoea	13/149 (8.7%)	14	21/152 (13.8%)	24
Oropharyngeal Pain	3/149 (2%)	3	8/152 (5.3%)	11
Skin and subcutaneous tissue disorders
Pruritus	9/149 (6%)	10	5/152 (3.3%)	5
Rash	8/149 (5.4%)	8	5/152 (3.3%)	6

Limitations/Caveats

[Not Specified]

More Information

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

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.