In the CARTITUDE-2 cohort A that included patients with MM who had received 1 to 3 previous lines of therapy and were lenalidomide-refractory, a single infusion of cilta-cel CAR T-cell therapy produced early and deep responses, with a manageable safety profile.
The multicohort, open-label, phase 2 CARTITUDE-2 study (NCT04133636) evaluated the safety and efficacy of the B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients with multiple myeloma (MM). Updated results of patients in CARTITUDE-2 cohort A who were lenalidomide-refractory were presented at the 2021 ASH Annual Meeting and summarized here.
The study enrolled patients who had progressive MM after 1 to 3 previous lines of therapy (LOT), including a proteasome inhibitor and immunomodulatory drug, were lenalidomide-refractory, and had no previous exposure to B-cell maturation antigen–targeting agents. A single cilta-cel infusion (target dose, 0.75 × 106 CAR-positive viable T-cells/kg) was given 5 to 7 days after the start of lymphodepletion (daily cyclophosphamide [300 mg/m2] and fludarabine [30 mg/m2] for 3 days). The primary end point was minimal residual disease (MRD) negativity at a sensitivity threshold of 10–5 (as assessed by next-generation sequencing). Secondary end points were overall response rate, duration of response, time and duration of MRD negativity, and incidence and severity of adverse events (AEs). The data cutoff date was October 8, 2021.
A total of 20 patients received cilta-cel infusion, of which 1 patient was treated in an outpatient setting. The median age of the study population was 60 years, and 65% were male. Patients received a median of 2 previous LOT; 60% received 1 or 2 previous LOT, and 40% received 3 previous LOT. All patients were exposed to a proteasome inhibitor, immunomodulatory drug, and dexamethasone; 95% to alkylating agents; and 65% to daratumumab; 95% of patients were refractory to the last LOT, and 40% were triple-class refractory.
At a median follow-up of 14.3 months, an overall response rate of 95% was achieved, with a complete response or better rate of 85% and a very good partial response or better rate of 90%. Median time to first response was 1.0 month, median time to best response was 2.6 months, and median time to complete response or better was 2.6 months. Median duration of response was not reached; 6-month progression-free survival rate was 95%. Among the 13 MRD-evaluable patients, MRD negativity at 10–5 was achieved by 92%.
Treatment-emergent AEs occurring in ≥20% of patients were mostly hematologic toxicities, including neutropenia, thrombocytopenia, anemia, lymphopenia, and leukopenia. Grade 3/4 hematologic AEs were neutropenia (95%), lymphopenia (65%), leukopenia (55%), anemia (45%), and thrombocytopenia (35%). Cytokine release syndrome (CRS) occurred in 95% of patients; the majority were grade 1/2, 10% were grade 3/4. Median time to CRS onset was 7 days, with a median duration of 4 days and the majority of events resolved within 7 days. CAR T-cell neurotoxicity was reported in 4 (20%) patients, which were all grade 1/2. Three (15%) patients had immune effector-cell–associated neurotoxicity syndrome (all grade 1/2); median time to onset was 8 days and median duration was 3 days. One death caused by COVID-19 was reported that was deemed treatment-related. Safety profile in the patient treated in an outpatient setting was manageable.
Based on these results, the investigators concluded that the cohort of patients with MM who had received 1 to 3 previous LOT and were lenalidomide-refractory who received a single cilta-cel infusion achieved early and deep responses with a manageable safety profile.
Source: Cohen YC, Cohen AD, Delforge M, et al. Efficacy and safety of ciltacabtagene autoleucel (cilta-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, in lenalidomide-refractory patients with progressive multiple myeloma after 1-3 prior lines of therapy: updated results from CARTITUDE-2. Blood. 2021;138(suppl 1):3866.