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

• Published in: Blood Vol. 141; no. 3; pp. 219 - 230
• Main Authors: Cohen, Adam D., Mateos, María-Victoria, Cohen, Yael C., Rodriguez-Otero, Paula, Paiva, Bruno, van de Donk, Niels W. C. J., Martin, Thomas, Suvannasankha, Attaya, De Braganca, Kevin C., Corsale, Christina, Schecter, Jordan M., Varsos, Helen, Deraedt, William, Wang, Liwei, Vogel, Martin, Roccia, Tito, Xu, Xiaoying, Mistry, Pankaj, Zudaire, Enrique, Akram, Muhammad, Nesheiwat, Tonia, Pacaud, Lida, Avivi, Irit, San-Miguel, Jesus
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 19.01.2023; The American Society of Hematology
• Subjects: Antibodies - therapeutic use; B-Cell Maturation Antigen; Clinical Trials and Observations; Humans; Immunotherapy; Immunotherapy, Adoptive - adverse effects; Multiple Myeloma - drug therapy; Neurotoxicity Syndromes - etiology; Receptors, Chimeric Antigen - therapeutic use
• ISSN: 0006-4971; 1528-0020
• DOI: 10.1182/blood.2022015526

•Cilta-cel, a BCMA-targeting chimeric antigen receptor−T-cell therapy, induced clinical responses in patients previously exposed to noncellular anti-BCMA therapies.•Results of this study may inform sequencing strategies for anti-BCMA therapies in patients with relapsed/refractory MM. [Display omitted] 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. B-cell maturation antigen (BCMA) is the target for multiple, new therapeutics in relapsed multiple myeloma (MM). Cohen and colleagues begin to address the question of sequencing by reporting a small series of patients treated with anti-BCMA chimeric antigen receptor (CAR) T cells after failure of anti-BCMA antibody-based biologicals. The authors report responses in 60% of patients and highlight the need for larger studies in this setting and a better understanding of the mechanisms of resistance to individual agents.