Isatuximab-pomalidomide-dexamethasone versus pomalidomide-dexamethasone in patients with relapsed and refractory multiple myeloma: final overall survival analysis
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-dexamet...
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| Published in | Haematologica (Roma) Vol. 109; no. 7; pp. 2239 - 2249 |
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| Main Authors | , , , , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
Italy
Fondazione Ferrata Storti
01.07.2024
Ferrata Storti Foundation |
| Subjects | |
| Online Access | Get full text |
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| Summary: | 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. |
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| Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 ObjectType-Undefined-3 PGR, AP, JS-M, MB, IS, XL, FS, PM, MAD, S-YH, JM, MC, and HMP were investigators in the study and contributed to data acquisition. PGR and AP were co-primary investigators of the ICARIA-MM study. PGR, SM, RZ, FD, and MCM contributed to the analysis, verification, and interpretation of data for the work. KCA was the chairman of the study Steering Committee. All authors revised the work for important intellectual content and assume responsibility for data integrity and the decision to submit this manuscript for publication, had full access to the study data, edited and reviewed manuscript drafts, and approved the final version for submission. Disclosures Contributions PGR reports research funding from Bristol Myers Squibb/Celgene, Karyopharm, Oncopeptides, and Takeda and participation on an entity’s board of directors or advisory committee for AstraZeneca, Bristol Myers Squibb/Celgene, GlaxoSmith-Kline, Karyopharm, Oncopeptides, Protocol Intelligence, Regeneron, Secura Bio, Sanofi, and Takeda. AP reports honoraria from AbbVie, Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, Sanofi, and Takeda. JS-M reports honoraria from AbbVie, Amgen, Bristol Myers Squibb/Cel-gene, GlaxoSmithKline, Haemalogix, Janssen, Karyopharm, Merck Sharp & Dohme, Novartis, Regeneron, Roche, Sanofi, SecuraBio, and Takeda. MB reports honoraria from Amgen, Celgene, Janssen, Sanofi, and Takeda and participation on an entity’s board of directors or advisory committee for Amgen, Janssen, Oncopeptides, and Takeda. IS reports honoraria from Amgen, Bristol Myers Squibb, Celgene, Janssen-Cilag, Novartis, PharmaMar, Sanofi, and Takeda. FS reports research funding from Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, and Targovax; honoraria from AbbVie, Amgen, Bristol Myers Squibb, Daiichi Sankyo, GlaxoSmithKline, Janssen, Novartis, Oncopeptides, Pfizer, Sanofi, SkyliteDX, and Takeda; and participation on an entity’s board of directors or advisory committee for AbbVie, Celgene, GlaxoSmithKline, Janssen, Oncopeptides, Sanofi, and Takeda. PM reports honoraria from AbbVie, Amgen, Celgene, GlaxoSmithKline, Janssen, and Sanofi. MAD reports honoraria from Amgen, BeiGene, Bristol Myers Squibb, Janssen, and Takeda. JM reports honoraria from Amgen, Bristol Myers Squibb/Celgene, Takeda, Janssen, and Sanofi and participation on an entity’s board of directors or advisory committees for Amgen, Bristol Myers Squibb/Celgene, Janssen, Oncopeptides, Sanofi, and Takeda. MC reports consulting fees from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, and Sanofi and honoraria from Amgen, Bristol Myers Squibb/Celgene, GlaxoSmithKline, Janssen, and Sanofi. SM, FD, RZ, and MCM are employees of Sanofi and may hold stock and/or stock options. KCA reports consulting fees from AstraZeneca, Janssen, Pfizer, and Precision Biosciences. XL, S-YH, and HMP have no conflicts of interest to disclose. |
| ISSN: | 0390-6078 1592-8721 1592-8721 |
| DOI: | 10.3324/haematol.2023.284325 |