TY - JOUR
T1 - Ide-cel vs standard regimens in triple-class–exposed relapsed and refractory multiple myeloma
T2 - updated KarMMa-3 analyses
AU - Ailawadhi, Sikander
AU - Arnulf, Bertrand
AU - Patel, Krina
AU - Cavo, Michele
AU - Nooka, Ajay K.
AU - Manier, Salomon
AU - Callander, Natalie
AU - Costa, Luciano J.
AU - Vij, Ravi
AU - Bahlis, Nizar J.
AU - Moreau, Philippe
AU - Solomon, Scott
AU - Abrahamsen, Ingerid Weum
AU - Baz, Rachid
AU - Broijl, Annemiek
AU - Chen, Christine
AU - Jagannath, Sundar
AU - Raje, Noopur
AU - Scheid, Christof
AU - Delforge, Michel
AU - Benjamin, Reuben
AU - Pabst, Thomas
AU - Iida, Shinsuke
AU - Berdeja, Jesús
AU - Giralt, Sergio
AU - Truppel-Hartmann, Anna
AU - Chen, Yanping
AU - Zhong, Xiaobo
AU - Wu, Fan
AU - Piasecki, Julia
AU - Eliason, Laurie
AU - Dhanda, Devender
AU - Felten, Jasper
AU - Caia, Andrea
AU - Cook, Mark
AU - Popa McKiver, Mihaela
AU - Rodríguez-Otero, Paula
N1 - Publisher Copyright:
© 2024 American Society of Hematology
PY - 2024/12/5
Y1 - 2024/12/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85205363169&partnerID=8YFLogxK
U2 - 10.1182/blood.2024024582
DO - 10.1182/blood.2024024582
M3 - Article
C2 - 39197072
AN - SCOPUS:85205363169
SN - 0006-4971
VL - 144
SP - 2389
EP - 2401
JO - Blood
JF - Blood
IS - 23
ER -