MM-153 Phase 2 CARTITUDE-2 Study (Cohort B): Updated Clinical Data and Biological Correlative Analyses of Ciltacabtagene Autoleucel (cilta-cel), a BCMA-Directed CAR-T Cell Therapy, in Patients With Multiple Myeloma (MM) and Early Relapse After Initial Therapy

Context: CARTITUDE-2 (NCT04133636) Cohort B is evaluating cilta-cel in patients with MM and early relapse after initial therapy. These patients have functionally high-risk disease and unmet medical needs, as early relapse post-ASCT is associated with a poor prognosis. Objective: To present updated results from CARTITUDE-2 Cohort B. Design: Phase 2, multicohort study. Patients: Eligible patients had MM, 1 prior LOT (PI and IMiD required), disease progression per IMWG, and no previous treatment with CAR-T/anti-BCMA therapies. Intervention: Single cilta-cel infusion (target dose 0.75×10⁶ CAR+ viable T-cells/kg) post lymphodepletion. Main Outcome Measures: Safety and efficacy were evaluated. Primary endpoint was MRD negativity at 10^-5. Management strategies were used to reduce the risk of movement/neurocognitive AEs (MNTs). Assessments included pharmacokinetics (PK) (C_max, T_max of CAR+ T-cell transgene levels in blood), CRS-related cytokine (eg, IL-6) levels over time, peak cytokine levels by response and CRS, association of cytokine levels with ICANS, and CAR+ T-cell CD4/CD8 ratio by response, CRS, and ICANS. Results: As of January 2022 (median follow-up 13.4 months), 19 patients (median age 58.0 years; 74% male; 79% with prior ASCT) received cilta-cel. ORR was 100% (90% ≥CR and 95% ≥VGPR). Median time to first response was 0.95 months and median time to best response was 5.1 months. Median DOR was not reached. Of 15 MRD-evaluable patients, 14 (93%) achieved MRD 10^-5 negativity. At 12 months, the event-free rate was 88.9% and PFS rate was 90%. CRS occurred in 16 (84.2%) patients (1 gr 4); median time to onset was 8 days. CRS resolved in all patients. 1 patient had ICANS (gr 1); 1 patient had MNT (gr 3; previously reported). 1 death occurred post-cilta-cel due to progressive disease (day 158). Preliminary PK data showed CAR-T cell peak expansion on day 13.1 and median persistence was 76.9 days. Conclusions: A single cilta-cel infusion resulted in deep and durable responses and manageable safety in functionally high-risk patients with MM and early clinical relapse/treatment failure to initial therapy. We will present updated and detailed PK/cytokine/CAR-T subset analyses and clinical correlations to provide novel insights into biological correlates of efficacy/safety in this population.