MM-119: Updated Results of Ciltacabtagene Autoleucel (Cilta-Cel), a B-Cell Maturation Antigen (BCMA)-Directed Chimeric Antigen Receptor T (CAR-T) Cell Therapy in Relapsed/Refractory Multiple Myeloma (RRMM)

Context Cilta-cel, a CAR-T cell therapy containing 2 BCMA-targeting single domain antibodies designed to confer high avidity binding, is being evaluated in the CARTITUDE-1 phase 1b/2 study. Objectives Provide updated results with a longer duration (median 12.4 months) of follow-up. Patients or Other Participants Patients had RRMM, measurable disease, ≥3 prior regimens (or double refractory to proteasome inhibitor and immunomodulatory drug) and received anti-CD38. Interventions A single cilta-cel infusion at the targeted dose of 0.75×106 (0.5–1.0×106) CAR+ viable T cells/kg was infused after cyclophosphamide/fludarabine lymphodepletion. Main Outcomes Measures The primary objectives were characterization of cilta-cel safety and confirmation of recommended phase 2 dose (phase 1b) and evaluation of efficacy (phase 2). Cytokine release syndrome (CRS) was graded by Lee 2014 and neurotoxicity by CTCAE in phase 1b; both were graded by ASTCT criteria in phase 2. Lee 2014 and CTCAE grading were mapped to ASTCT criteria for CRS and ICANS, respectively. Response was assessed per IMWG criteria. Results At 12.4-month median follow-up, 97 patients (median of 6 prior lines) received cilta-cel. Overall response rate was 97% (95% CI, 91–99), and 67% had stringent complete response (sCR). Median time to first response was 1 month (range, 1–9), median time to ≥CR was 2 months (range, 1–15), and median duration of response was not reached. Of 57 minimal residual disease (MRD)-evaluable patients, 93% were MRD-negative at 10–5. The 12-month progression-free survival (PFS) and overall survival rates (95% CI) were 77% (66–84) and 89% (80–94), respectively; median PFS was not reached. Grade 3/4 hematologic AEs included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). CRS occurred in 95% of patients (4% grade 3/4), with median time to onset of 7 days (range, 1–12). CAR-T cell neurotoxicity occurred in 21% patients (10% grade ≥3). Fourteen deaths occurred during the study: 0 ≤30 days, 2 ≤100 days, and 12 >100 days post-infusion, of which 5 were from disease progression and 4 from treatment-related AEs. Conclusions A single cilta-cel dose yielded early, deep, and durable responses with manageable safety in heavily pre-treated patients with RRMM. Acknowledgement The study was funded by Janssen Research & Development, LLC and Legend Biotech, Inc.