Scientific publications
Efficacy and safety of cilta-cel in patients with progressive MM after exposure to other BCMA-targeting agents
Adam D Cohen 1 , Maria-Victoria Mateos 2 , Yael C Cohen 3 , Paula Rodriguez-Otero 4 , Bruno Paiva 5 , Niels W C J van de Donk 6 , Thomas G Martin 7 , Attaya Suvannasankha 8 , Kevin C De Braganca 9 , Christina Corsale 10 , Jordan M Schecter 11 , Helen Varsos 10 , William Deraedt 12 , Liwei Wang 10 , Martin Vogel 13 , Tito Roccia 14 , Xiaoying Xu 15 , Pankaj Mistry 16 , Enrique Zudaire 17 , Muhammad Akram 18 , Tonia Nesheiwat 18 , Lida Pacaud 19 , Irit Avivi 3 , Jesus San-Miguel 20
Abstract
B-cell maturation antigen (BCMA)-targeting therapies, including bispecific antibodies (BsAbs) and antibody-drug conjugates (ADC), 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 non‑cellular 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); 16 (80%) were refractory to prior anti-BCMA therapy. At a median follow-up of 11.3 months (range, 0.6-16.0), 7/20 (35%) patients were MRD-negative (7/10 [70.0%] in the MRD-evaluable subset).
Overall response rate (95% 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 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 have exhausted other therapies. This trial was registered at www.clinicaltrials.gov as #NCT04133636.
CITATION Blood. 2023 Jan 19;141(3):219-230.
doi: 10.1182/blood.2022015526