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

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.

Graphical abstract

Figure 1.

Patient disposition. ∗Three were due to Parkinson disease, 2 to acute respiratory failure (COVID-19), 1 to subarachnoid hemorrhage (not treatment related), and 1 to Clostridium difficile colitis (treatment related).

Figure 2.

Response to cilta-cel. Response among responders (A) and in all patients with previous exposure to antibody-drug conjugate (ADC) (B) or BsAb (C). Classification is based on the last anti−B-cell maturation antigen therapy used if patients received >1 therapy. NE, not evaluable; SD, stable disease. ^†Patient was treated with ADC for 1 day. ^‡Patients with extramedullary plasmacytomas. ^§Patient was treated with 2 different ADCs. ^||Patient received BsAb first and ADC later.

Figure 3.

Progression-free survival. Kaplan-Meier curves showing progression-free survival in the overall cohort (A), the antibody-drug conjugate (ADC)-exposed patients (B), and the BsAb-exposed patients (C). ^†Classification is based on the last anti-BCMA therapy used if patients received >1 therapy.