Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma
- Author(s)
- San-Miguel, J; Dhakal, B; Yong, K; Spencer, A; Anguille, S; Mateos, MV; Fernandez de Larrea, C; Martinez-Lopez, J; Moreau, P; Touzeau, C; Leleu, X; Avivi, I; Cavo, M; Ishida, T; Kim, SJ; Roeloffzen, W; van de Donk, NWCJ; Dytfeld, D; Sidana, S; Costa, LJ; Oriol, A; Popat, R; Khan, AM; Cohen, YC; Ho, PJ; Griffin, J; Lendvai, N; Lonardi, C; Slaughter, A; Schecter, JM; Jackson, CC; Connors, K; Li, K; Zudaire, E; Chen, D; Gilbert, J; Yeh, TM; Nagle, S; Florendo, E; Pacaud, L; Patel, N; Harrison, SJ; Einsele, H;
- Details
- Publication Year 2023-07-27,Volume 389,Issue #4,Page 335-347
- Journal Title
- New England Journal of Medicine
- Publication Type
- Research article
- Abstract
- BACKGROUND: Ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, is effective in heavily pretreated patients with relapsed or refractory multiple myeloma. We investigated cilta-cel in earlier treatment lines in patients with lenalidomide-refractory disease. METHODS: In this phase 3, randomized, open-label trial, we assigned patients with lenalidomide-refractory multiple myeloma to receive cilta-cel or the physician's choice of effective standard care. All the patients had received one to three previous lines of treatment. The primary outcome was progression-free survival. RESULTS: A total of 419 patients underwent randomization (208 to receive cilta-cel and 211 to receive standard care). At a median follow-up of 15.9 months (range, 0.1 to 27.3), the median progression-free survival was not reached in the cilta-cel group and was 11.8 months in the standard-care group (hazard ratio, 0.26; 95% confidence interval [CI], 0.18 to 0.38; P<0.001). Progression-free survival at 12 months was 75.9% (95% CI, 69.4 to 81.1) in the cilta-cel group and 48.6% (95% CI, 41.5 to 55.3) in the standard-care group. More patients in the cilta-cel group than in the standard-care group had an overall response (84.6% vs. 67.3%), a complete response or better (73.1% vs. 21.8%), and an absence of minimal residual disease (60.6% vs. 15.6%). Death from any cause was reported in 39 patients and 46 patients, respectively (hazard ratio, 0.78; 95% CI, 0.5 to 1.2). Most patients reported grade 3 or 4 adverse events during treatment. Among the 176 patients who received cilta-cel in the as-treated population, 134 (76.1%) had cytokine release syndrome (grade 3 or 4, 1.1%; no grade 5), 8 (4.5%) had immune effector cell-associated neurotoxicity syndrome (all grade 1 or 2), 1 had movement and neurocognitive symptoms (grade 1), 16 (9.1%) had cranial nerve palsy (grade 2, 8.0%; grade 3, 1.1%), and 5 (2.8%) had CAR-T-related peripheral neuropathy (grade 1 or 2, 2.3%; grade 3, 0.6%). CONCLUSIONS: A single cilta-cel infusion resulted in a lower risk of disease progression or death than standard care in lenalidomide-refractory patients with multiple myeloma who had received one to three previous therapies. (Funded by Janssen and Legend Biotech; CARTITUDE-4 ClinicalTrials.gov number, NCT04181827.).
- Publisher
- Massachusetts Medical Society
- Keywords
- Humans; Lenalidomide/adverse effects; *Multiple Myeloma/drug therapy/mortality; Neurotoxicity Syndromes; Progression-Free Survival; *B-Cell Maturation Antigen/immunology; *Immunotherapy, Adoptive/methods; *Antineoplastic Agents, Immunological/therapeutic use; Drug Resistance, Neoplasm
- Department(s)
- Clinical Haematology
- PubMed ID
- 37272512
- Publisher's Version
- https://doi.org/10.1056/NEJMoa2303379
- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2023-10-12 05:13:36
Last Modified: 2024-07-16 04:40:07