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


Authors: Ailawadhi, S.; Arnulf, B.; Patel, K.; Cavo, M.; Nooka, A. K.; Manier, S.; Callander, N.; Costa, L. J.; Vij, R.; Bahlis, N. J.; Moreau, P.; Solomon, S.; Abrahamsen, I. W.; Baz, R.; Broijl, A.; Chen, C.; Jagannath, S.; Raje, N.; Scheid, C.; Delforge, M.; Benjamin, R.; Pabst, T.; Iida, S.; Berdeja, J.; Giralt, S.; Truppel-Hartmann, A.; Chen, Y.; Zhong, X.; Wu, F.; Piasecki, J.; Eliason, L.; Dhanda, D.; Felten, J.; Caia, A.; Cook, M.; Popa McKiver, M.; Rodríguez-Otero, P.
Article Title: Ide-cel vs standard regimens in triple-class–exposed relapsed and refractory multiple myeloma: Updated KarMMa-3 analyses
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. © 2024 American Society of Hematology
Journal Title: Blood
Volume: 144
Issue: 23
ISSN: 0006-4971
Publisher: American Society of Hematology  
Date Published: 2024-12-05
Start Page: 2389
End Page: 2401
Language: English
DOI: 10.1182/blood.2024024582
PUBMED: 39197072
PROVIDER: scopus
DOI/URL:
Notes: Article -- Source: Scopus
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  1. Sergio Andres Giralt
    1054 Giralt