Safety and Efficacy of Standard of Care Ciltacabtagene Autoleucel for Relapsed/Refractory Multiple Myeloma
Menée aux Etats-Unis dans un contexte de vie réelle à partir de données portant sur 236 patients atteints d'un myélome multiple réfractaire ou récidivant, cette étude évalue l'efficacité, du point de vue du taux de réponse et de la survie sans progression, et la toxicité du ciltacabtagène autoleucel
Ciltacabtagene autoleucel (cilta-cel) CAR-T therapy was approved in 2022 for patients with relapsed/refractory multiple myeloma (RRMM). We report outcomes with cilta-cel in the standard-of-care setting. Patients with RRMM who underwent leukapheresis for cilta-cel manufacturing between 3/1/2022-12/31/2022 at 16 US academic medical centers were included. RESULTS: 255 patients underwent leukapheresis and 236 (92.5%) received cilta-cel. Of leukapheresed patients, 56% would not have met CARTITUDE-1 trial eligibility criteria. Manufacturing failure rates at first attempt and overall were 6% and 1%, respectively. Median prior lines of therapy were 6. In treated patients (N=236), cytokine release syndrome was seen in 75% (>= grade 3: 5%), immune effector cell-associated neurotoxicity syndrome in 14% (>= grade 3: 4%), and delayed neurotoxicity in 10%. Best overall and >= CR rates were as follows: infused patients (N=236): 89% and 70%; patients receiving conforming CAR-T product (N=191) 94% and 74%; conforming CAR-T product with fludarabine/cyclophosphamide lymphodepletion (N=152): 95% and 76%, respectively. Non-relapse mortality was 10%, most commonly from infection. After median follow-up of 13 months from CAR-T, median progression-free survival (PFS) was not reached, with 12- month estimate being 68% (95% CI: 62-74%). High ferritin levels, high-risk cytogenetics, and extramedullary disease were independently associated with inferior PFS, with a signal for prior BCMA-TT (p=0.08). Second primary malignancies (SPMs) excluding non-melanoma skin cancers were seen in 5.5% and myeloid malignancies/acute leukemia in 1.7%. We observed a favorable efficacy profile of standard of care cilta-cel in RRMM despite more than half the patients not meeting CARTITUDE-1 eligibility criteria.
Blood 2023