Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor (CAR) T-cell therapy directed against 2 discrete B-cell maturation antigen (BCMA) epitopes. Updated data from the phase 1b portion of CARTITUDE-1, which is evaluating cilta-cel in a patient population in the United States, along with initial phase 2 data, are presented. The primary objective of the phase 1b portion was to assess safety and determine a dose to be used in the phase 2 investigation. The primary objective of the phase 2 portion was to evaluate efficacy.
Eligible adults in this study had measurable disease, Eastern Cooperative Oncology Group performance status ≤1, received ≥3 prior regimens, or were double-refractory to a proteasome inhibitor and an immunomodulatory drug. Patients also had received an anti-CD38 antibody. After lymphodepletion with cyclophosphamide and fludarabine daily for 3 days followed by 2 to 4 days of rest, a single infusion of cilta-cel at a target dose of 0.75 × 106 (range, 0.5-1.0 × 106) CAR+ viable T-cells/kg was administered.
A total of 97 patients received cilta-cel (phase 1b, 29; phase 2, 68) at a median dose of 0.71 × 106 (range, 0.51-1.95 × 106) CAR+ viable T-cells/kg at the time of the latest data cutoff. The median age of patients in the study was 61 years, and 59% of patients were male. Patients had received a median of 6 prior lines of therapy, with 83.5% of patients being penta-exposed, 87.6% triple-refractory, 42.3% penta-refractory, and 99% refractory to their last line of therapy. The median follow-up duration in this study was 8.8 months.
The observed overall response rate was 96.9%. A complete response rate was observed in 67% of patients, a very good partial response rate in 25.8%, and a partial response rate in 4.1%. M protein was reduced in all patients. The median time to first response was 1.0 month (range, 0.9-5.8; 80.4% ≤1.0 months), and the median time to complete response or better was 1.8 months (range, 0.9-12.5; 74.1% ≤3.0 months), with responses deepening over time. At the time of data cutoff, the median duration of response was not reached. Of 57 patients evaluable for minimal residual disease (MRD), 93% were MRD negative at 10-5. The 12-month progression-free survival (PFS) rate was 76.6%. The median PFS has not yet been reached. The 12-month overall survival (OS) rate was 88.5%, and the median OS has also not been reached.
There were 9 deaths in the study resulting from adverse events (1 for all the following: cytokine release syndrome [CRS]/hemophagocytic lymphohistiocytosis, neurotoxicity, respiratory failure, pneumonia, and lung abscess; 2 for both sepsis and/or septic shock and acute myelogenous leukemia) and 5 of which resulted from progressive disease. A total of 94.8% of patients experienced CRS (grade 3/4, 4.1%), 95.9% of patients experienced neutropenia (all but 1 being grade 3/4), 81.4% of patients experienced anemia (grade 3/4, 68.0%), and 79.4% of patients experienced thrombocytopenia (grade 3/4, 59.8%). Median time to onset and duration of CRS were 7.0 days and 4.0 days, respectively. Neurotoxicity due to CAR T-cell therapy was experienced by 20.6% of patients (grade 3/4, 10.3%). Maximum peripheral expansion of CAR+ T-cells was observed at 14 days, and 67% of patients at 6 months had cilta-cel CAR+ T-cells below the level of quantification (2 cells/μL) in peripheral blood.
The preliminary results from the phase 1b/2 CARTITUDE-1 study revealed early, deep, and durable responses in these heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM). The safety profile was consistent with prior studies. Cilta-cel is currently being evaluated in other multiple myeloma populations.
Abstract 177. ASH 2020. December 5, 2020. CARTITUDE-1: Phase 1b/2 study of ciltacabtagene autoleucel, a B-cell maturation antigen–directed chimeric antigen receptor T cell therapy, in relapsed/refractory multiple myeloma.