OAB-023: Efficacy and safety of ciltacabtagene autoleucel, a BCMA-directed CAR-T cell therapy, in patients with progressive multiple myeloma after 1–3 prior lines of therapy: Initial results from CARTITUDE-2

Abstract

<h3>Background</h3> Ciltacabtagene autoleucel (cilta-cel) is a CAR-T cell therapy expressing two B-cell maturation antigen (BCMA)-targeting, single-domain antibodies. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating the safety and efficacy of cilta-cel in various clinical settings for patients (pts) with multiple myeloma (MM) and exploring suitability of outpatient administration. Initial results from Cohort A are presented here. <h3>Methods</h3> Pts from Cohort A had progressive MM after 1–3 prior lines of therapy (LOT), including a proteasome inhibitor (PI) and immunomodulatory drug (IMiD), were lenalidomide refractory, and had not received BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×10⁶ CAR+ viable T cells/kg) was given 5–7 days after start of lymphodepletion (daily cyclophosphamide [300 mg/m²] and fludarabine [30 mg/m²] for 3 days). Minimal residual disease (MRD) negativity at 10^-5 was the primary objective, and response rates (per IMWG) and safety (per CTCAE; CRS and ICANS by ASTCT) were secondary outcomes. <h3>Results</h3> At data cutoff (Feb 2021), the median follow-up was 5.8 months (2.5–9.8). Twenty pts (65% male; median age 60 years [38–75]) had received cilta-cel, with 1 pt treated in an outpatient setting. The median number of prior LOT was 2 (1–3): <3 prior LOT (n=12) and 3 prior LOT (n=8). All pts were exposed to PI, IMiD, and dexamethasone, 95% had received alkylating agents, and 65% had received daratumumab. 95% were refractory to the last LOT, and 40% were triple-class refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved sCR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 month (0.7–3.3), and median time to best response was 1.9 months (0.9–5.1). Median duration of response was not reached. All 4 pts with MRD-evaluable samples at 10^-5 at the time of data cutoff were MRD-negative. Hematologic adverse events (≥20%) were neutropenia (95%; grade [gr] 3/4: 90%), thrombocytopenia (80%; gr 3/4: 35%), anemia (65%; gr 3/4: 40%), lymphopenia (60%; gr 3/4: 55%), and leukopenia (55%; all gr 3/4). 85% of pts had CRS (gr 3/4: 10%). Median time to CRS onset was 7 days (5–9), with a median duration of 3.5 days (2–11). CAR-T cell neurotoxicity occurred in 20% of pts (all gr 1/2). ICANS was reported in 3 pts (1 gr 1 and 2 gr 2) with median time to onset of 8 days (7–11) and median duration of 2 days (1–2). One pt had gr 2 facial paralysis with onset at 29 days and duration of 51 days. One death from COVID-19 was assessed as treatment-related by investigator. For the pt treated in an outpatient setting, the safety profile was manageable. <h3>Conclusion</h3> Early and deep responses with manageable safety were demonstrated after a single cilta-cel infusion at the recommended phase 2 dose. Updated findings will inform suitability of outpatient treatment for this study and for the CARTITUDE-2 and CARTITUDE-4 studies.