Efficacy and safety of cilta-cel in patients with progressive multiple myeloma after exposure to other BCMA-targeting agents

Adam D. Cohen, María Victoria Mateos, Yael C. Cohen, Paula Rodriguez-Otero, Bruno Paiva, Niels W.C.J. van de Donk, Thomas Martin, Attaya Suvannasankha, Kevin C. De Braganca, Christina Corsale, Jordan M. Schecter, Helen Varsos, William Deraedt, Liwei Wang, Martin Vogel, Tito Roccia, Xiaoying Xu, Pankaj Mistry, Enrique Zudaire, Muhammad AkramTonia Nesheiwat, Lida Pacaud, Irit Avivi, Jesus San-Miguel*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

B-cell maturation antigen (BCMA)–targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADCs), are promising treatments for multiple myeloma (MM), but disease may progress after their use. CARTITUDE-2 is a phase 2, multicohort study evaluating the safety and efficacy of cilta-cel, an anti-BCMA chimeric antigen receptor T therapy, in various myeloma patient populations. Patients in cohort C progressed despite treatment with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and noncellular anti-BCMA immunotherapy. A single cilta-cel infusion was given after lymphodepletion. The primary end point was minimal residual disease (MRD) negativity at 10−5. Overall, 20 patients were treated (13 ADC exposed; 7 BsAb exposed; 1 in the ADC group also had prior BsAb exposure). Sixteen (80%) were refractory to prior anti-BCMA therapy. At a median follow-up of 11.3 months (range, 0.6-16.0), 7 of 20 (35%) patients were MRD negative (7 of 10 [70.0%] in the MRD-evaluable subset). Overall response rate (95% confidence interval [CI]) was 60.0% (36.1-80.9). Median duration of response and progression-free survival (95% CI) were 11.5 (7.9—not estimable) and 9.1 (1.5—not estimable) months, respectively. The most common adverse events were hematologic. Cytokine release syndrome occurred in 12 (60%) patients (all grade 1-2); 4 had immune effector cell-associated neurotoxicity syndrome (2 had grade 3-4); none had parkinsonism. Seven (35%) patients died (3 of progressive disease, 4 of adverse events [1 treatment related, 3 unrelated]). Cilta-cel induced favorable responses in patients with relapsed/refractory MM and prior exposure to anti-BCMA treatment who had exhausted other therapies. This trial was registered at www.clinicaltrials.gov as NCT04133636.

Original languageEnglish
Pages (from-to)219-230
Number of pages12
JournalBlood
Volume141
Issue number3
DOIs
StatePublished - 19 Jan 2023

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