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.