Results of the 18-month follow-up of the phase 1b/2 CARTITUDE-1 trial indicated that a single infusion of cilta-cel produced early, deep, and durable responses in heavily pretreated patients with RRMM, with manageable toxicity.
The phase 1b/2 CARTITUDE-1 study is evaluating the B-cell maturation antigen–directed chimeric antigen receptor (CAR) T-cell therapy ciltacabtagene autoleucel (cilta-cel) in patients with relapsed/refractory multiple myeloma (RRMM). Updated results from an 18-month follow-up were presented at the 2021 International Myeloma Workshop and summarized here.
The study enrolled patients with multiple myeloma, who had received ≥3 previous regimens (or were double-refractory to a proteasome inhibitor and immunomodulatory drug) and who had received an anti-CD38 antibody. Eligible patients received a single infusion of cilta-cel (target dose: 0.75 × 106 CAR-positive viable T-cells/kg), administered 5 to 7 days after lymphodepletion (300 mg/m2 cyclophosphamide and 30 mg/m2 fludarabine daily for 3 days). The primary objectives of phase 1b were to assess safety and establish the recommended phase 2 dose, whereas that of phase 2 was to evaluate antitumor activity. The data cutoff date was February 11, 2021.
At data cutoff, a total of 97 patients received cilta-cel infusion. Patients had received a median of 6 previous lines of therapy. An overall response rate of 97.9% was achieved, with stringent complete response of 80.4% and very good partial response or better of 94.8%. Median time to first response was 1 month (range, 0.9-10.7 months); median time to complete response or better was 2.6 months (range, 0.9-15.2 months). Median duration of response was 21.8 months. In minimal residual disease–evaluable patients (N = 61), 91.8% were minimal residual disease-negative at 10–5. The 18-month progression-free survival rate was 66% and the 18-month overall survival rate was 80.9%. Median progression-free survival was 22.8 months for all patients and was not reached for patients with stringent complete response.
Grade 3/4 adverse events (AEs) were predominantly hematologic toxicities; hematologic AEs that occurred in ≥20% of patients included neutropenia (95%), anemia (68%), leukopenia (61%), thrombocytopenia (60%), and lymphopenia (50%). Cytokine release syndrome (CRS) occurred in 95% of patients; 4% of these were grade 3/4 severity. The median time to onset of CRS was 7 days, and median duration was 4 days (range, 1-14 days, except 1 patient with 97 days of duration). CRS resolved in all cases except 1; there was 1 report of grade 5 CRS/hemophagocytic lymphohistiocytosis. CAR T-cell neurotoxicity occurred in 21% of patients; grade ≥3 neurotoxicity occurred in 10% of patients. A total of 21 deaths were reported, the majority (N = 19) of which occurred after 100 days of cilta-cel infusion and 2 within 100 days. Of the 21 deaths, 6 were treatment-related, and 5 were caused by AEs unrelated to treatment.
Results of the 18-month follow-up of the CARTITUDE-1 trial indicated that a single infusion of cilta-cel produced early, deep, and durable responses in heavily pretreated patients with RRMM, with manageable toxicity.
Source: Jagannath S, Berdeja JG, Jakubowiak A, et al. Updated results from CARTITUDE-1: ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T (CAR-T) cell therapy, in relapsed/refractory multiple myeloma (RRMM). Clin Lymphoma Myeloma Leuk. 2021;21(suppl 2):S15-S16.