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

Plasma Cell Myeloma Clinical Trial

— ICARIA-MM  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02990338
• Other study ID #: EFC14335
• Secondary ID: U1111-1180-62622
• Status: Completed
• Phase: Phase 3
• Start date: December 22, 2016
• Est. completion date: November 1, 2023

Study information

• Verified date: November 2023
• Source: Sanofi
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 307
• Est. completion date: November 1, 2023
• Est. primary completion date: November 22, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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*10^9/L).

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

• Total bilirubin superior to 2*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*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.

Related Conditions & MeSH terms

• Multiple Myeloma
• Neoplasms, Plasma Cell
• Plasma Cell Myeloma

Intervention

Drug:
• Isatuximab
Pharmaceutical form: solution for infusion Route of administration: intravenous
• Pomalidomide
Pharmaceutical form: capsule Route of administration: oral
• Dexamethasone
Pharmaceutical form: tablets or solution for infusion Route of administration: oral or intravenous

Locations

Country	Name	City	State
Australia	Investigational Site Number : 0360002	Melbourne	Victoria
Australia	Investigational Site Number : 0360005	Melbourne	Victoria
Australia	Investigational Site Number : 0360006	Richmond	Victoria
Australia	Investigational Site Number : 0360004	St Leonards	New South Wales
Australia	Investigational Site Number : 0360001	Waratah	New South Wales
Belgium	Investigational Site Number : 0560003	Antwerpen
Belgium	Investigational Site Number : 0560002	Brussel
Belgium	Investigational Site Number : 0560004	Gent
Belgium	Investigational Site Number : 0560001	Leuven
Canada	Investigational Site Number : 1240001	Montreal	Quebec
Canada	Investigational Site Number : 1240004	Montreal	Quebec
Canada	Investigational Site Number : 1240005	Sherbrooke	Quebec
Czechia	Investigational Site Number : 2030005	Brno
Czechia	Investigational Site Number : 2030004	Hradec Kralove
Czechia	Investigational Site Number : 2030001	Olomouc
Czechia	Investigational Site Number : 2030002	Ostrava - Poruba
Czechia	Investigational Site Number : 2030003	Praha 2
Denmark	Investigational Site Number : 2080002	Aalborg
France	Investigational Site Number : 2500021	Bayonne
France	Investigational Site Number : 2500008	Caen
France	Investigational Site Number : 2500009	Dijon
France	Investigational Site Number : 2500017	Grenoble
France	Investigational Site Number : 2500013	La Roche Sur Yon
France	Investigational Site Number : 2500003	Lille
France	Investigational Site Number : 2500023	Limoges
France	Investigational Site Number : 2500019	Montpellier Cedex
France	Investigational Site Number : 2500002	Nantes
France	Investigational Site Number : 2500015	Paris
France	Investigational Site Number : 2500016	Paris
France	Investigational Site Number : 2500005	Pessac
France	Investigational Site Number : 2500004	Pierre Benite
France	Investigational Site Number : 2500007	POITIERS Cedex
France	Investigational Site Number : 2500025	Reims
France	Investigational Site Number : 2500014	Rennes
France	Investigational Site Number : 2500001	TOULOUSE Cedex 9
France	Investigational Site Number : 2500012	Tours
France	Investigational Site Number : 2500018	Vandoeuvre-les-nancy
Germany	Investigational Site Number : 2760001	Leipzig
Greece	Investigational Site Number : 3000001	Athens
Greece	Investigational Site Number : 3000002	Athens
Greece	Investigational Site Number : 3000005	Athens
Greece	Investigational Site Number : 3000004	Patra
Greece	Investigational Site Number : 3000003	Thessaloniki
Hungary	Investigational Site Number : 3480001	Budapest
Hungary	Investigational Site Number : 3480003	Budapest
Hungary	Investigational Site Number : 3480002	Debrecen
Italy	Investigational Site Number : 3800001	Bologna
Italy	Investigational Site Number : 3800010	Catania
Italy	Investigational Site Number : 3800009	Firenze
Italy	Investigational Site Number : 3800008	Genova
Italy	Investigational Site Number : 3800002	Milano
Italy	Investigational Site Number : 3800007	Milano
Italy	Investigational Site Number : 3800006	Padova
Italy	Investigational Site Number : 3800004	Terni
Italy	Investigational Site Number : 3800003	Torino
Japan	Investigational Site Number : 3920006	Kyoto-shi	Kyoto
Japan	Investigational Site Number : 3920001	Nagoya-shi	Aichi
Japan	Investigational Site Number : 3920003	Okayama-shi	Okayama
Japan	Investigational Site Number : 3920004	Sapporo-shi	Hokkaido
Japan	Investigational Site Number : 3920005	Shibukawa-shi	Gunma
Japan	Investigational Site Number : 3920002	Shibuya-ku	Tokyo
Japan	Investigational Site Number : 3920007	Shizuoka	Sunto Gun
Japan	Investigational Site Number : 3920008	Suwa-shi	Nagano
Korea, Republic of	Investigational Site Number : 4100007	Hwasun-gun	Jeollanam-do
Korea, Republic of	Investigational Site Number : 4100006	Incheon
Korea, Republic of	Investigational Site Number : 4100001	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100002	Seoul	Seoul-teukbyeolsi
Korea, Republic of	Investigational Site Number : 4100005	Seoul
New Zealand	Investigational Site Number : 5540002	Auckland
New Zealand	Investigational Site Number : 5540004	Dunedin	Otago
New Zealand	Investigational Site Number : 5540003	Hamilton	Waikato
New Zealand	Investigational Site Number : 5540001	Takapuna	Auckland
Norway	Investigational Site Number : 5780001	Oslo
Poland	Investigational Site Number : 6160002	Chorzow	Slaskie
Poland	Investigational Site Number : 6160005	Krakow	Malopolskie
Poland	Investigational Site Number : 6160003	Lublin	Lubuskie
Poland	Investigational Site Number : 6160001	Warszawa	Mazowieckie
Portugal	Investigational Site Number : 6200004	Coimbra
Portugal	Investigational Site Number : 6200002	Lisboa
Portugal	Investigational Site Number : 6200001	Porto
Russian Federation	Investigational Site Number : 6430001	Moscow
Russian Federation	Investigational Site Number : 6430002	Moscow
Russian Federation	Investigational Site Number : 6430004	Moscow
Slovakia	Investigational Site Number : 7030001	Bratislava
Spain	Investigational Site Number : 7240001	Barcelona	Barcelona [Barcelona]
Spain	Investigational Site Number : 7240003	Madrid
Spain	Investigational Site Number : 7240002	Pamplona	Navarra
Spain	Investigational Site Number : 7240004	Salamanca
Spain	Investigational Site Number : 7240006	Santander	Cantabria
Spain	Investigational Site Number : 7240005	Santiago de Compostela	A Coruña [La Coruña]
Sweden	Investigational Site Number : 7520004	Luleå
Sweden	Investigational Site Number : 7520005	Uddevalla
Taiwan	Investigational Site Number : 1580004	Kaohsiung
Taiwan	Investigational Site Number : 1580002	Taichung
Taiwan	Investigational Site Number : 1580001	Taipei
Taiwan	Investigational Site Number : 1580003	Taoyuan
Turkey	Investigational Site Number : 7920001	Ankara
Turkey	Investigational Site Number : 7920002	Antalya
Turkey	Investigational Site Number : 7920003	Istanbul
Turkey	Investigational Site Number : 7920004	Istanbul
Turkey	Investigational Site Number : 7920005	Istanbul
Turkey	Investigational Site Number : 7920006	Istanbul
Turkey	Investigational Site Number : 7920008	Izmir
Turkey	Investigational Site Number : 7920010	Izmir
Turkey	Investigational Site Number : 7920009	Kayseri
Turkey	Investigational Site Number : 7920007	Kocaeli
United Kingdom	Investigational Site Number : 8260001	London	London, City Of
United Kingdom	Investigational Site Number : 8260002	London	London, City Of
United Kingdom	Investigational Site Number : 8260003	London	London, City Of
United States	Dana Farber Site Number : 8400006	Boston	Massachusetts
United States	BRCR Medical Center Inc. Site Number : 8400002	Plantation	Florida

Sponsors (1)

Lead Sponsor	Collaborator
Sanofi

Countries where clinical trial is conducted

United States,  Australia,  Belgium,  Canada,  Czechia,  Denmark,  France,  Germany,  Greece,  Hungary,  Italy,  Japan,  Korea, Republic of,  New Zealand,  Norway,  Poland,  Portugal,  Russian Federation,  Slovakia,  Spain,  Sweden,  Taiwan,  Turkey,  United Kingdom, 

References & Publications (2)

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

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

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Progression Free Survival (PFS)	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.	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)
Secondary	Overall Response Rate (ORR): Percentage of Participants With Disease Response as Per Independent Response Committee (IRC)	ORR (IMWG criteria): percentage of participants with stringent complete response(sCR), complete response (CR), very good partial response (VGPR), and partial response (PR) as best overall response, assessed by IRC. sCR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates plus normal free light chain(FLC)ratio(0.26-1.65), absence of clonal cells in bone marrow biopsy.CR:negative immunofixation on serum and urine,disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.VGPR: serum and urine M-protein detectable by immunofixation, not on electrophoresis/,>=90% reduction in serum M-protein plus urine M-protein level <100mg/24h/,>=90% decrease in SPD compared to baseline in soft tissue plasmacytoma. PR: >=50% reduction of serum M-protein and reduction in 24h urinary M-protein by >=90%/<200mg/24h,if present at baseline,>=50% reduction in the size (SPD) of soft tissue plasmacytomas.	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)
Secondary	Percentage of Participants With Best Overall Response (BOR) as Per Independent Response Committee	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.	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)
Secondary	Percentage of Participants With Very Good Partial Response (VGPR) or Better as Per Independent Response Committee	VGPR rate was defined as the percentage of participants achieving a VGPR or better as BOR. VGPR was defined as serum and urine M-protein detectable by immunofixation but not on electrophoresis or >=90% reduction in serum M-protein plus urine M-protein level <100 mg/24 h or >=90% decrease in the sum of maximal perpendicular diameter compared to baseline in soft tissue plasmacytoma. BOR was defined as the best sequential response, using the IRC's assessment of response, from the start of treatment until disease progression (provided that the progression is subsequently confirmed in case of progression requiring confirmation), death, initiation of further anti-myeloma treatment, or cut-off date, whichever occurs first. CR: negative immunofixation on serum and urine, disappearance of any soft tissue plasmacytomas,<5% plasma cells in bone marrow aspirates.	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)
Secondary	Clinical Benefit Rate (CBR): Percentage of Participants With Clinical Benefit as Per Independent Response Committee	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.	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)
Secondary	Overall Survival (OS): Final Analysis	OS was defined as the time from the date of randomization to death from any cause. In the absence of confirmation of death, survival time was censored at the last date participant was known to be alive or at the cut-off date, whichever comes first. This pre-specified final analysis was performed when the 220 OS events were met.	From the date of randomization to date of death from any cause or data cut-off date, whichever was earlier (maximum duration 245.6 weeks)
Secondary	Time to Progression (TTP) as Per Independent Response Committee	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.	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)
Secondary	Progression Free Survival in High Risk Cytogenetic Population	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.	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)
Secondary	Duration of Response (DOR) as Per Independent Response Committee	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.	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)
Secondary	Time to First Response (TT1R) as Per Independent Response Committee	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.	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)
Secondary	Time to Best Response (TTBR) as Per Independent Response Committee	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.	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)
Secondary	Number of Participants With Minimal Residual Disease (MRD)	MRD was assessed by next-generation sequencing in bone marrow samples from participants who achieved CR, to determine the depth of response at the molecular level. IMWG criteria for CR: Negative immunofixation on the serum and urine, disappearance of any soft tissue plasmacytomas, and <5% plasma cells in bone marrow aspirates. MRD was classified as positive or negative at the minimum sensitivity of 1 in 10^5 nucleated cells. MRD negativity was defined as the absence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening. MRD positivity was defined as the presence of the dominant clonotype sequence(s) identified in the bone marrow aspirate collected at screening.	Up to 76.7 weeks
Secondary	Number of Participants With Treatment Emergent Adverse Events (TEAEs) and Serious Adverse Events (SAEs)	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.	From randomization up to 30 days after last dose of study drug (maximum duration up to 241.6 weeks for Pd arm and 245.6 weeks for IPd arm)
Secondary	Pharmacokinetics (PK) Parameter: Plasma Concentration of Isatuximab at End of Infusion (CEOI)	CEOI was defined as the plasma concentration at end of infusion.	End of infusion on Cycle(C)1 Day(D)1 and Cycle1 Day 15; Cycle 2 Day 1; and Cycle 4 Day 1
Secondary	Pharmacokinetic Parameter: Accumulation Ratio of Isatuximab at Concentration at the End of Infusion (CEOI)	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.	End of infusion on Cycle 1 Day 1, Cycle 2 Day 1, and Cycle 4 Day 1
Secondary	Pharmacokinetic Parameter: Plasma Concentration of Isatuximab at 1 Hour After End of Infusion (CEOI+1 Hour)	CEOI+1 hour was defined as the plasma concentration of isatuximab at 1 hour after end of infusion.	Cycle 1:1 hour after End of Infusion on Day 1; Cycle 4:1 hour after End of Infusion on Day 1
Secondary	PK Parameter: Plasma Concentration of Isatuximab at Ctrough	Trough Concentration (Ctrough) is the concentration prior to study drug administration.	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])
Secondary	PK Parameter: Accumulation Ratio of Isatuximab at Trough Concentration (Ctrough)	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.	Pre-infusion on Cycle 1 Day 8, Cycle 2 Day 1, and Cycle 4 Day 1
Secondary	Number of Participants With Anti-drug Antibodies (ADA)	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.	From randomization up to 60 days after last dose of study drug (maximum duration 76.7 weeks)
Secondary	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	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.	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary	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	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	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary	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	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.	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary	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	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.	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)
Secondary	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)	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.	Baseline, Day 1 of each cycle (Cycle 3, Cycle 6, Cycle 9, and Cycle 17)