P-240: Efficacy and Safety of Cilta-Cel and T-Cell Phenotype Analyses in Patients With Relapsed/Refractory Multiple Myeloma and Prior Non-Cellular Anti-BCMA Therapy: Phase 2 CARTITUDE-2 Cohort C

Introduction: B-cell maturation antigen (BCMA)-targeting therapies are promising treatments (tx) for patients (pts) with multiple myeloma (MM), and data are required to understand tx sequencing to optimize pt outcomes. CARTITUDE-2 (NCT04133636) is a phase 2, multicohort study evaluating the efficacy and safety of ciltacabtagene autoleucel (cilta-cel), an approved anti-BCMA chimeric antigen receptor (CAR)-T cell therapy, in several MM pt populations. CARTITUDE-2 Cohort C enrolled pts with heavily pretreated relapsed/refractory MM who were previously exposed to a noncellular anti-BCMA tx. We present efficacy and safety results for cohort C pts with a median follow-up of 18.0 months (mo).

Methods: Cohort C pts had progressive MM after tx with a proteasome inhibitor, immunomodulatory drug, anti-CD38 antibody, and a noncellular BCMA-targeting agent. A single cilta-cel infusion (target dose: 0.75×10⁶ CAR+ viable T cells/kg [range: 0.5–1.0×10⁶ CAR+ viable T cells/kg]) was administered 5–7 days post lymphodepletion. The primary endpoint was minimal residual disease (MRD) negativity at 10⁻⁵ threshold. Secondary endpoints included response rates (per International Myeloma Working Group criteria) and safety.

Results: As of June 1, 2022, 20 pts (13 ADC, 7 BsAb exposed; 1 pt in the ADC group had prior BsAb tx) received cilta-cel. 6 pts (30%) had anti-BCMA tx as their last line of therapy (LOT; n=4 ADC, n=2 BsAb). At baseline, median age was 62.5 years (range, 44–81); 60% were male; 15% had high-risk cytogenetics (all del17p); 25% had extramedullary disease; received a median of 8 (range, 4–13) prior LOT. Median cilta‑cel dose administered was 0.61×10⁶ (range, 0.21×10⁶–0.83×10⁶) CAR+ viable T cells/kg; 1 pt received a below-target dose range. At a median follow-up of 18.0 mo (range, 0.6–22.7), 7 of 10 evaluable pts (70%) in the full cohort were MRD negative at 10⁻⁵ threshold (5 of 7 [71.4%] in the ADC group, and 2 of 3 [66.7%] in the BsAb group). The overall response rate was 60%; ADC, 61.5%; BsAb, 57.1%. Median duration of response was 12.3 mo (95% CI, 7.2–NE); ADC, 13.3 mo (7.2–NE); BsAb, 8.2 mo (4.4–NE). Median progression-free survival was 9.1 mo (95% CI, 1.5–13.8); ADC, 9.5 mo (1.0–15.2); BsAb, 5.3 mo (0.6–NE). The most common adverse events (AEs) were hematologic.12 pts had cytokine release syndrome (6 in ADC, 6 in BsAb, [all grade 1/2]); resolved in all. 4 pts had immune effector cell-associated neurotoxicity syndrome (2 in ADC [grade 3/4]; 2 in BsAb [1 grade 3/4]); resolved in 3. No pt had movement or neurocognitive tx-emergent AE/parkinsonism. Total of 12 deaths occurred (7 in ADC; 5 in BsAb [1 due to tx-related C. difficile colitis]).

Conclusions: These results in the context of published data, including CARTITUDE-1, suggest that cilta-cel in anti-BCMA naive pts offers better outcomes, although this interpretation needs to be cautioned by the small number of pts. Updated results and additional correlative analyses will be presented.