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247 Isatuximab Plus Pomalidomide/Low-Dose Dexamethasone Versus Pomalidomide/Low-Dose Dexamethasone in Patients with Relapsed/Refractory Multiple Myeloma (ICARIA-MM): Characterization of Subsequent Antimyeloma Therapies

Program: Oral and Poster Abstracts
Type: Oral
Session: 652. Multiple Myeloma and Plasma Cell Dyscrasias: Clinical and Epidemiological: Relapsed and/or Refractory Myeloma (RRMM)
Hematology Disease Topics & Pathways:
Biological therapies, Research, clinical trials, Plasma Cell Disorders, Clinical Research, Diseases, Therapies, Lymphoid Malignancies, Monoclonal Antibody Therapy
Saturday, December 10, 2022: 2:00 PM

Paul G. Richardson, MD1,2, Aurore Perrot, MD, PhD3*, Jesús San-Miguel, MD, PhD4, Meral Beksac, MD5, Ivan Spicka, MD, Prof, PhD6*, Xavier Leleu, MD, PhD7, Fredrik Schjesvold, MD, PhD8, Philippe Moreau, MD9*, Meletios A. Dimopoulos, MD10, Jeffrey SY Huang, M.D., Ph.D.11*, Jiri Minarik, MD12, Michele Cavo, MD13*, H. Miles Prince, MD, FRACP, FRCPA14, Sandrine Macé, PhD15*, Laure Malinge16*, Franck Dubin, PharmD17*, Mony Morisse, MD, MSc18* and Kenneth C. Anderson, MD19

1Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA
2Department of Medical Oncology, Jerome Lipper Multiple Myeloma Center, Dana-Farber Cancer Institute, Boston, MA
3Department of Hematology, Toulouse University Institute of Cancer, Toulouse, France
4Clínica Universidad de Navarra, CIMA, CIBERONC, IDISNA, Pamplona, Spain
5Department of Hematology, Ankara University, Ankara, Turkey
6General Faculty Hospital and First Faculty of Medicine, Charles University, Prague, Czech Republic
7Service d'Hématologie et Thérapie Cellulaire, CHU and CIC Inserm 1402, Poitiers, France
8Oslo Myeloma Center, Department of Hematology, Oslo University Hospital, Oslo, Norway, and KG Jebsen Center for B Cell Malignancies, University of Oslo, Oslo, Norway
9Hematology Department, University Hospital Hôtel-Dieu, Nantes, France
10Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece
11Department of Hematology, National Taiwan University Hospital, Taipei, Taiwan
12Department of Hemato-oncology, Faculty Hospital and Faculty of Medicine and Dentistry, Palacký University, Olomouc, Czech Republic
13Seràgnoli Institute of Hematology, Bologna University School of Medicine, Bologna, Italy
14Immunology and Molecular Oncology, Epworth Healthcare, University of Melbourne, Melbourne, VIC, Australia
15Sanofi, Vitry-Sur-Seine, France
16Sanofi on behalf of Aixial, Boulogne-Billancourt, France
17Sanofi, Vitry-sur-Seine, France
18Sanofi, Cambridge
19Jerome Lipper Multiple Myeloma Center, Department of Medical Oncology, Dana Farber Cancer Institute, Harvard Medical School,, Boston, MA

Introduction: Based on the primary analysis of the Phase 3 ICARIA-MM study (NCT02990338), isatuximab (Isa), an anti-CD38 monoclonal antibody, is approved in combination with pomalidomide and dexamethasone (Pd) in several countries for patients with relapsed and refractory multiple myeloma (RRMM) who have received at least 2 prior treatments, including lenalidomide and a proteasome inhibitor. Here, we describe updated, longer-term efficacy data following subsequent therapy.

Methods: Patients were randomized 1:1 to Isa-Pd (n=154) or Pd (n=153), with stratification by age (<75 vs ≥75) and number of prior lines (2–3 versus more than >3). Isa 10 mg/kg was administered weekly for the first 4-week cycle and every 2 weeks thereafter. In each cycle, both treatment arms received pomalidomide 4 mg (days 1-21) and weekly dexamethasone 40 mg (days 1, 8, 15, and 22). Treatment was given until progressive disease, unacceptable adverse events, or patient choice. The final overall survival analysis was planned when 220 death events occurred.

Results: As of March 14, 2022, 16 (10.4%) patients receiving Isa-Pd and 3 (2.0%) patients receiving Pd were still on treatment; 101 (65.6%) and 117 (76.5%) patients, respectively, discontinued treatment due to progressive disease. Median treatment duration was longer with Isa-Pd vs Pd (47.6 vs 24.0 weeks). After a median 52.4 months of follow-up, a clinically meaningful overall survival (OS) benefit was observed in favor of Isa-Pd vs Pd after 220 events (Jan 27, 2022; median: 24.6 vs 17.7 months; hazard ratio 0.776 [95% CI: 0.594–1.1015]; one-sided P=0.0319; significance level: P=0.02). Further antimyeloma treatment was given to 102 (66.2%) patients receiving Isa-Pd and 119 (77.8%) patients receiving Pd (regardless of the reason for treatment discontinuation in both arms), with a median of 2 and 1 further regimens, respectively. Of the patients receiving subsequent therapy, 22.5% (23/102) in the Isa-Pd arm and 59.7% (71/119) in the Pd arm received daratumumab. The most common further antimyeloma treatments for patients in the Isa-Pd arm were corticosteroids (n=88/102; 86.3%), alkylating agents (n=71/102; 69.6%), and proteasome inhibitors (n=70/102; 68.6%); the most common treatment received in the first subsequent line was a proteasome inhibitor (n=54/102; 52.9%). The most common further antimyeloma treatments for patients in the Pd arm were corticosteroids (n=94/119; 79.0%), monoclonal antibodies (n=75/119; 63.0%), and proteasome inhibitors (n=69/119; 58.0%); the most common treatment received in the first subsequent line was daratumumab (n=52/119; 43.7%). The overall response rate (ORR) for the first subsequent line of therapy was 28.8% (23/80) for the Isa-Pd arm and 35.3% (30/85) for the Pd arm. The ORR for patients receiving daratumumab-based regimens as the first subsequent line was 25.0% (2/8) for the Isa-Pd arm and 40.5% (17/42) for the Pd arm. The ORR for patients receiving daratumumab as monotherapy or with steroids in any subsequent line was 12.5% (1/8) for the Isa-Pd arm and 36.7% (11/30) for the Pd arm. The ORR for patients receiving daratumumab in combination with immunomodulatory agents, alkylating agents, or proteasome inhibitors in any subsequent line was 28.6% (4/14) for the Isa-Pd arm and 44.8% (13/29) for the Pd arm. Progression-free survival (PFS) on first subsequent line for patients receiving daratumumab was 2.2 months for the Isa-Pd arm and 5.7 months for the Pd arm. PFS on first subsequent line for patients receiving treatment excluding daratumumab was 4.6 months for the Isa-Pd arm and 5.2 months for the Pd arm.

Conclusions: This analysis demonstrates that the majority of patients with RRMM require multiple lines of subsequent therapy, even after receiving a triplet combination that includes a monoclonal antibody. The immediate use of an anti-CD38 monoclonal antibody with currently available combinations appears to be less effective in the Isa-Pd arm. The more frequent use of subsequent daratumumab in Pd (59.7%) compared with Isa-Pd (22.5%) may have affected the power to detect statistically significant OS given the sample size, as well as reflecting the efficacy of this approach in the management of RRMM.

Funding: Sanofi.

Disclosures: Richardson: GlaxoSmithKline: Consultancy; Abbvie: Consultancy; Protocol Intelligence: Consultancy; AstraZeneca: Consultancy; Regeneron: Consultancy; Secura Bio: Consultancy; Sanofi: Consultancy; Karyopharm: Consultancy, Research Funding; Takeda: Consultancy, Research Funding; Celgene/BMS: Consultancy, Research Funding; Oncopeptides: Consultancy, Research Funding. Perrot: Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Honoraria; Pfizer: Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria, Membership on an entity's Board of Directors or advisory committees; BMS: Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Abbvie: Honoraria. San-Miguel: Abbvie, Amgen, BMS, Celgene, GSK, Haemalogix, Janssen-Cilag, Karyopharm, MSD, Novartis, Takeda, Regeneron, Roche, Sanofi, and SecuraBio: Consultancy, Other: Advisory Board. Beksac: Sanofi: Research Funding, Speakers Bureau; Celgene: Speakers Bureau; Amgen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Janssen: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Takeda: Membership on an entity's Board of Directors or advisory committees, Speakers Bureau; Oncopeptides: Membership on an entity's Board of Directors or advisory committees. Spicka: Novartis: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding; PharmaMar: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding. Leleu: Takeda: Honoraria; Sanofi: Honoraria; Amgen: Honoraria; Pfizer: Honoraria; Amgen, Merck, BMS, GSK, Janssen, Oncopeptide, Takeda, Roche, Novartis, AbbVie, Sanofi, Gilead, Pfizer, Harpoon Therapeutic, Regeneron, Iteos: Consultancy, Honoraria; BMS: Honoraria; Janssen: Honoraria; Amgen, BMS/Celgene, Janssen, Takeda, Novartis, Sanofi, Merck, Oncopeptide, Karyopharm, Roche, Abbvie, Carsgen, GSK, and Harpoon Therapeutics: Honoraria. Schjesvold: Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen-Cilag: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novartis: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; AbbVie: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Daiichi Sankyo: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Targovax: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Skylite DX: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; GlaxoSmithKline: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Moreau: AbbVie, Amgen, Celgene, Janssen, Oncopeptides, Sanofi: Honoraria. Dimopoulos: Beigene: Honoraria; Takeda: Honoraria; Janssen: Honoraria; Amgen: Honoraria; BMS: Honoraria. Minarik: Abbvie: Consultancy, Honoraria; Amgen: Consultancy, Honoraria; BSM: Consultancy, Honoraria; Celgene: Consultancy, Honoraria; EUSA Pharma: Consultancy, Honoraria; GSK: Consultancy, Honoraria; JANSSEN: Consultancy, Honoraria; SANOFI: Consultancy, Honoraria; TAKEDA: Consultancy, Honoraria. Cavo: AbbVie, Amgen, Bristol Myers Squibb/Celgene, Pfizer, GlaxoSmithKline, Sanofi, Roche, Takeda: Consultancy, Honoraria; Janssen: Honoraria, Speakers Bureau. Macé: Sanofi: Current Employment. Malinge: Sanofi: Current Employment, Current holder of stock options in a privately-held company. Dubin: Sanofi: Current Employment. Morisse: Sanofi: Current Employment. Anderson: Amgen: Membership on an entity's Board of Directors or advisory committees; Starton: Membership on an entity's Board of Directors or advisory committees; Raqia: Other: Scientific founder ; Pfizer: Membership on an entity's Board of Directors or advisory committees; C4 Therapeutics: Other: Scientific founder ; Precision Biosciences: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Window: Membership on an entity's Board of Directors or advisory committees; NextRNA: Other: Scientific founder ; OncoPep: Other: Scientific founder ; AstraZeneca: Membership on an entity's Board of Directors or advisory committees; Dynamic Cell Therapy: Current holder of stock options in a privately-held company, Membership on an entity's Board of Directors or advisory committees; Mana Therapeutics: Membership on an entity's Board of Directors or advisory committees.

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