The primary and prespecified updated analyses of ICARIA-MM (clinicaltrial gov. Identifier: NCT02990338) demonstrated improved progression-free survival (PFS) and a benefit in overall survival (OS) was reported with the addition of isatuximab, an anti-CD38 monoclonal antibody, to pomalidomide-dexamethasone (Pd) in patients with relapsed/refractory multiple myeloma. Here, we report the final OS analysis. This multicenter, randomized, open-label, phase III study included patients who had received and failed ≥2 previous therapies, including lenalidomide and a proteasome inhibitor. Between January 10, 2017, and February 2, 2018, 307 patients were randomized (1:1) to isatuximab-pomalidomide-dexamethasone (Isa-Pd; N=154) or Pd (N=153), stratified based on age (<75 vs. ≥75 years) and number of previous lines of therapy (2-3 vs. >3). At data cutoff for the final OS analysis after 220 OS events (January 27, 2022), median follow-up duration was 52.4 months. Median OS was 24.6 months (95% confidence interval [CI]: 20.3-31.3) with Isa-Pd and 17.7 months (95% CI: 14.4- 26.2) with Pd (hazard ratio=0.78; 95% CI: 0.59-1.02; 1-sided P=0.0319). Despite subsequent daratumumab use in the Pd group and its potential benefit on PFS in the first subsequent therapy line, median PFS2 was significantly longer with Isa-Pd versus Pd (17.5 vs. 12.9 months; log-rank 1-sided P=0.0091). In this analysis, Isa-Pd continued to be efficacious and well tolerated after follow-up of approximately 52 months, contributing to a clinically meaningful, 6.9-month improvement in median OS in patients with relapsed/refractory multiple myeloma.

CHU de Toulouse IUCT O Université de Toulouse UPS Service d'Hématologie Toulouse

Clínica Universidad de Navarra Navarra CCUN CIMA IDISNA CIBER ONC Pamplona

Department of Clinical Therapeutics School of Medicine National and Kapodistrian University of Athens School of Medicine Athens Greece

Department of Hemato Oncology Faculty of Medicine and Dentistry Palacky University and University Hospital Olomouc Olomouc Czech Republic

Department of Hematology Ankara University Ankara Turkey

Department of Hematology National Taiwan University Hospital Taipei Taiwan

General Faculty Hospital Prague Czech Republic; 1st Faculty of Medicine Charles University Prague Czech Republic

Hematology Department CHU Nantes Nantes

Immunology and Molecular Oncology Epworth Healthcare University of Melbourne Melbourne VIC Australia

IRCCS Azienda Ospedaliero Universitaria di Bologna Seràgnoli Institute of Hematology and the Department of Medical and Surgical Sciences Bologna University School of Medicine Bologna Italy

Jerome Lipper Multiple Myeloma Center Department of Medical Oncology Dana Farber Cancer Institute Harvard Medical School Boston MA

Oslo Myeloma Center Department of Haematology Oslo University Hospital Oslo Norway; KG Jebsen Center for B Cell Malignancies University of Oslo Oslo Norway

Sanofi Cambridge MA

Sanofi Vitry sur Seine

Service d'Hématologie et Thérapie Cellulaire CHU and CIC Inserm 1402 Poitiers Cedex

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NCT02990338