•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.