Scientific publications
Cilta-cel or Standard Care in Lenalidomide-Refractory Multiple Myeloma. Scientific Publication
Jesús San-Miguel 1 , Binod Dhakal 1 , Kwee Yong 1 , Andrew Spencer 1 , Sébastien Anguille 1 , María-Victoria Mateos 1 , Carlos Fernández de Larrea 1 , Joaquín Martínez-López 1 , Philippe Moreau 1 , Cyrille Touzeau 1 , Xavier Leleu 1 , Irit Avivi 1 , Michele Cavo 1 , Tadao Ishida 1 , Seok Jin Kim 1 , Wilfried Roeloffzen 1 , Niels W C J van de Donk 1 , Dominik Dytfeld 1 , Surbhi Sidana 1 , Luciano J Costa 1 , Albert Oriol 1 , Rakesh Popat 1 , Abdullah M Khan 1 , Yaël C Cohen 1 , P Joy Ho 1 , James Griffin 1 , Nikoletta Lendvai 1 , Carolina Lonardi 1 , Ana Slaughter 1 , Jordan M Schecter 1 , Carolyn C Jackson 1 , Kaitlyn Connors 1 , Katherine Li 1 , Enrique Zudaire 1 , Diana Chen 1 , Jane Gilbert 1 , Tzu-Min Yeh 1 , Sarah Nagle 1 , Erika Florendo 1 , Lida Pacaud 1 , Nitin Patel 1 , Simon J Harrison 1 , Hermann Einsele 1
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.).
CITATION N Engl J Med. 2023 Jul 27;389(4):335-347. doi: 10.1056/NEJMoa2303379. Epub 2023 Jun 5
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