CARTITUDE-2: Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a BCMA-directed CAR T-cell therapy, in patients with progressive multiple myeloma (MM) after one to three prior lines of therapy.

8013 Background: Cilta-cel is a CAR T-cell therapy expressing two BCMA-targeting, single-domain antibodies designed to confer avidity. The multicohort, phase 2 CARTITUDE-2 study (NCT04133636) is evaluating cilta-cel safety and efficacy in various clinical settings for patients (pts) with MM and exploring suitability of outpatient administration. Here, we present initial results from Cohort A. Methods: Cohort A pts 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 no prior exposure to BCMA-targeting agents. A single cilta-cel infusion (target dose: 0.75×10 6 CAR+ viable T cells/kg) was given 5–7 days (d) after start of lymphodepletion (daily cyclophosphamide 300 mg/m 2 and fludarabine 30 mg/m 2 for 3 d). The primary objective was minimal residual disease (MRD) 10 -5 negativity. Secondary outcomes were response rates (IMWG) and safety (per CTCAE; CRS and ICANS by ASTCT). Results: As of Feb 2021 data cutoff (median follow-up: 5.8 months mo; range: 2.5–9.8 mos), 20 pts (65% male; median age 60 years 38–75) received cilta-cel; 1 pt was treated in an outpatient setting. Pts received a median of 2 prior LOT (1–3); 12 pts received < 3 prior lines and 8 received 3 prior LOT. All pts were exposed to PI, IMiD, and dexamethasone, 95% to alkylating agents, and 65% to daratumumab. The majority (95%) were refractory to the last LOT; 40% were triple refractory. Overall response rate was 95% (95% CI: 75–100), 75% (95% CI: 51–91) achieved stringent CR/CR, and 85% (95% CI: 62–97) achieved ≥VGPR. Median time to first response was 1.0 mo (0.7–3.3); median time to best response was 1.9 mo (0.9–5.1). Median duration of response was not reached. All pts (n = 4) with MRD-evaluable samples at 10 -5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%; 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). CRS occurred in 85% of pts; 10% were gr 3/4. Median time to CRS onset was 7 d (5–9), with a median duration of 3.5 d (2–11). CAR T-cell neurotoxicity occurred in 20% of pts (all gr 1/2). Three pts had ICANS (1 gr 1; 2 gr 2); median time to onset was 8 d (7–11) and median duration was 2 d (1–2). One pt had gr 2 facial paralysis; time to onset was 29 d with a duration of 51 d. One death occurred due to COVID-19 (assessed as treatment (tx)-related by investigator). Safety profile was manageable in the pt treated in an outpatient setting. Conclusions: A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in pts with MM who had 1–3 prior LOT. Updated efficacy and safety findings will inform suitability of outpatient tx in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study. Clinical trial information: NCT04133636.