Cilta-cel is a CAR-T cell therapy that expresses 2 BCMA-targeting single-domain antibodies, designed to confer avidity. In the multicohort, phase 2 CARTITUDE-2 study (NCT04133636), the safety and efficacy of cilta-cel in various clinical settings and suitability of outpatient administration was explored in patients with multiple myeloma.

Patients enrolled in 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 were naïve to 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). The primary outcome was minimal residual disease (MRD) 10-5 negativity. Secondary outcomes were response rates (per IMWG criteria) and safety (per CTCAE; CRS and ICANS by ASTCT).

As of the February 2021 data cutoff (median follow-up: 5.8 months [2.5–9.8]), 20 patients (65% male; median age 60 years [38–75]) received cilta-cel; 1 patient was treated in an outpatient setting. Patients (n = 12: <3 prior LOT; n = 8: 3 prior LOT) received a median of 2 (1–3) prior LOT. All patients 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-class 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 month (0.7–3.3); median time to best response was 1.9 month (0.9–5.1). Median duration of response was not reached. All patients (n = 4) with MRD-evaluable samples at 10-5 at data cutoff were MRD-negative. Hematologic AEs ≥20% were neutropenia (95%; grade 3/4: 90%), thrombocytopenia (80%; grade 3/4: 35%), anemia (65%; grade 3/4: 40%), lymphopenia (60%; grade 3/4: 55%), and leukopenia (55%; all grade 3/4). 85% of patients had CRS; 10% were grade 3/4. 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 patients (all grade 1/2). Three patients had ICANS (n = 1: grade 1; n = 2: grade 2); median time to onset was 8 days (7–11) and median duration was 2 days (1–2). One patient had grade 2 facial paralysis; time to onset was 29 days with a duration of 51 days. One death occurred due to Covid-19 (assessed as treatment-related by investigator). The safety profile was manageable in the patient who was treated in an outpatient setting.

Updated efficacy and safety findings will inform suitability of outpatient treatment in this and other cohorts of CARTITUDE-2 as well as the CARTITUDE-4 study.

A single cilta-cel infusion at the recommended phase 2 dose led to early and deep responses with a manageable safety profile in patients with MM who had 1–3 prior LOT.