The Phase 2 CARTITUDE-2 Trial: Updated Efficacy and Safety of Ciltacabtagene Autoleucel in Patients with Multiple Myeloma and 1-3 Prior Lines of Therapy (Cohort A) and with Early Relapse after First Line Treatment (Cohort B)

Introduction CARTITUDE-2 (NCT04133636), a phase 2, multicohort study evaluating safety and efficacy of the anti–B-cell maturation antigen (BCMA) chimeric antigen receptor (CAR)-T cell therapy ciltacabtagene autoleucel (cilta-cel) in patients (pts) with multiple myeloma (MM). We present updated efficacy and safety data from CARTITUDE-2 cohorts A and B with a median follow-up (MFU) of ∼29 mo. Methods Pts in both cohorts A (1–3 prior lines of therapy [LOT] and lenalidomide [len] refractory) and B (early relapse [≤12 mo] after autologous stem cell transplant [ASCT] or start of antimyeloma treatment if no transplant) naive to CAR-T and/or anti-BCMA therapies received cilta-cel infusion (target dose 0.75 × 106 CAR+ viable T cells/kg) 5–7 days after lymphodepletion. The primary endpoint was minimal residual disease (MRD) negativity (10−5 threshold). Management strategies were implemented to reduce risk of movement and neurocognitive treatment-emergent adverse events (MNTs). Results As of April 2023, 20 pts in cohort A received cilta-cel (MFU, 29.9 mo; 35% high-risk cytogenetics; median 2 prior LOT; 95% refractory to last LOT; 40% triple-class refractory [TCE]; 85% prior ASCT). At the same data cut-off, 19 pts in cohort B received cilta-cel (MFU, 27.9 mo; 16% high-risk cytogenetics; 79% refractory to last LOT; 16% TCE; 79% prior ASCT). Most MRD-evaluable pts achieved MRD negativity, and some sustained it (Table 1). Cilta-cel led to overall response rates of 95% (complete response or better [≥CR], 90%) and 100% (≥CR, 90%), in cohort A (n=20) and cohort B (n=19), respectively. Median progression-free survival (PFS) was not reached; 24-mo PFS rates were 75% in cohort A and 73% in cohort B. In cohort A, hematologic treatment-emergent adverse events (TEAEs) (17.1–29.9-mo MFU) included grade (gr) 3/4 leukopenia (n=1), gr 3/4 lymphopenia (n=2), and gr 3/4 thrombocytopenia (n=1); no new pts in cohort A reported CAR-T cell neurotoxicity (Table 2). In cohort B, no new pts had MNTs or hematologic TEAEs, but other neurotoxicity (gr 2 sensory loss) occurred (n=1; all gr, 5 total; 26%) and resolved; second primary malignancy (gr 4 choroid melanoma) occurred (n=1; all gr, 2 total; 11%). One new death (total 5) occurred in cohort A on day 666 (progressive disease), and 1 new death (total 4) occurred in cohort B on day 749 (cardiac arrest; not treatment related). Conclusions Longer-term FU data show that pts treated with cilta-cel in earlier LOT, both with len-refractory MM after 1–3 LOT (cohort A) and early relapse (cohort B), had deep, durable responses. No new CAR-T–related safety signals, except for 1 additional CAR-T cell neurotoxicity in cohort B, were reported. Cohort A provides insight into longer-term survival outcomes that may be expected in the CARTITUDE-4 trial (similar population with shorter FU to date). Cohort B data highlight the durable efficacy of cilta-cel in pts with early relapse where there is unmet need.