Ide-cel vs standard regimens in triple-class-exposed relapsed and refractory multiple myeloma: updated KarMMa-3 analyses.
Type: article
Abstract: Outcomes are poor in triple-class-exposed (TCE) relapsed/refractory multiple myeloma (RRMM). In the phase 3 KarMMa-3 (clinicaltrials.gov; NCT03651128) trial, patients with TCE RRMM and 2-4 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 endpoint; 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 (95% CI) was 41.4 (30.9-not reached [NR]) vs 37.9 (23.4-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 RRMM. NCT03651128.
DOI: 10.48620/8379
Authors: Ailawadhi, Sikander, Arnulf, Bertrand, Patel, Krina K, Cavo, Michele, Nooka, Ajay K, Manier, Salomon, Callander, Natalie S, Costa, Luciano J, Vij, Ravi, Bahlis, Nizar J, Moreau, Philippe, Solomon, Scott R, Abrahamsen, Ingerid Weum, Baz, Rachid C, Broijl, Annemiek, Chen, Christine, Jagannath, Sundar, Raje, Noopur, Scheid, Christof, Delforge, Michel, Benjamin, Reuben, Pabst, Thomas, Iida, Shinsuke, Berdeja, Jesus G, Giralt, Sergio A, Truppel-Hartmann, Anna, Chen, Yanping, Zhong, Xiaobo, Wu, Fan, Piasecki, Julia, Eliason, Laurie, Dhanda, Devender S, Felten, Jasper, Caia, Andrea, Cook, Mark, Popa-Mckiver, Mihaela, Rodriguez-Otero, Paula
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W6948490113
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