Ide-cel vs standard regimens in triple-class–exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses

Sikander Ailawadhi, Bertrand Arnulf, Krina Patel, Michele Cavo, Ajay K. Nooka, Salomon Manier, Natalie Callander, Luciano J. Costa, Ravi Vij, Nizar J. Bahlis, Philippe Moreau, Scott Solomon, Ingerid Weum Abrahamsen, Rachid Baz, Annemiek Broijl, Christine Chen, Sundar Jagannath, Noopur Raje, Christof Scheid, Michel DelforgeReuben Benjamin, Thomas Pabst, Shinsuke Iida, Jesús Berdeja, Sergio Giralt, Anna Truppel-Hartmann, Yanping Chen, Xiaobo Zhong, Fan Wu, Julia Piasecki, Laurie Eliason, Devender Dhanda, Jasper Felten, Andrea Caia, Mark Cook, Mihaela Popa McKiver, Paula Rodríguez-Otero

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Outcomes are poor in triple-class–exposed (TCE) relapsed and refractory multiple myeloma (R/RMM). In the phase 3 KarMMa-3 trial, patients with TCE R/RMM and 2 to 4 prior regimens were randomized 2:1 to idecabtagene vicleucel (ide-cel) or standard regimens (SRs). An interim analysis (IA) demonstrated significantly longer median progression-free survival (PFS; primary end point; 13.3 vs 4.4 months; P <.0001) and higher overall response rate (ORR) with ide-cel vs SRs. At final PFS analysis (median follow-up, 30.9 months), ide-cel further improved median PFS vs SRs (13.8 vs 4.4 months; hazard ratio [HR], 0.49; 95% confidence interval [CI], 0.38-0.63). PFS benefit with ide-cel vs SRs was observed regardless of number of prior lines of therapy, with greatest benefit after 2 prior lines (16.2 vs 4.8 months, respectively). ORR benefit was maintained with ide-cel vs SRs (71% vs 42%; complete response, 44% vs 5%). Patient-centric design allowed crossover from SRs (56%) to ide-cel upon progressive disease, confounding overall survival (OS) interpretation. At IA of OS, median was 41.4 (95% CI, 30.9 to not reached [NR]) vs 37.9 (95% CI, 23.4 to NR) months with ide-cel and SRs, respectively (HR, 1.01; 95% CI, 0.73-1.40); median OS in both arms was longer than historical data (9-22 months). Two prespecified analyses adjusting for crossover showed OS favoring ide-cel. This trial highlighted the importance of individualized bridging therapy to ensure adequate disease control during ide-cel manufacturing. Ide-cel improved patient-reported outcomes vs SRs. No new safety signals were reported. These results demonstrate the continued favorable benefit-risk profile of ide-cel in early-line and TCE R/RMM. This trial was registered at www.ClinicalTrials.gov as #NCT03651128.

Original languageEnglish
Pages (from-to)2389-2401
Number of pages13
JournalBlood
Volume144
Issue number23
DOIs
StatePublished - Dec 5 2024

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