In heavily pretreated patients with relapsed/refractory multiple myeloma (RRMM), preliminary results from the phase 1b/2 CARTITUDE-1 study show early, deep, and durable responses with a single low-dose infusion of ciltacabtagene autoleucel (cilta-cel) and a safety profile consistent with prior studies.
Previously shown in a phase 1 study to induce deep, durable responses with manageable toxicity in patients with RRMM was cilta-cel, a chimeric antigen receptor (CAR) T-cell therapy directed against 2 discrete B-cell maturation antigen (BCMA) epitopes to increase binding strength. Updated data from the phase 1b portion of CARTITUDE-1, evaluating cilta-cel in this 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 for use in phase 2 investigation. The primary objective of the phase 2 portion was to evaluate efficacy.
Eligible adults 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, and received an anti-CD38 antibody. After apheresis, bridging therapy was allowed, and 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 after lymphodepletion with cyclophosphamide and fludarabine daily for 3 days followed by 2 to 4 days of rest.
Through May 20, 2020, 97 patients received cilta-cel (phase 1b: 29; phase 2: 68); 59% were male; median age was 61 years. Patients received a median of 6 prior lines of therapy; 83.5% of patients were penta-exposed, 87.6% triple refractory, 41.2% penta refractory, and 97.9% refractory to their last line of therapy. Median follow-up duration was 8.8 months.
The observed overall response rate was 94.8% consisting of a stringent complete response rate of 55.7%, a very good partial response rate of 32.0%, and a partial response rate of 7.2%. In all patients, a reduction in M-protein was achieved. Median time to first response was 1.0 month, and median time to complete response or better was 1.8 months, whereas deepening of responses over time was observed. Median duration of response was not reached by data cutoff time. Of 52 patients evaluable for minimal residual disease (MRD), 94.2% were MRD-negative at 10-6. The 6-month progression-free survival (PFS) rate (landmark) and median PFS were 87.4%, and not reached, respectively. The 6-month overall survival (OS) rate and median OS were 93.8% and not reached.
In the study, 10 deaths were reported, 8 of which were caused by adverse events (n = 1 for all of the following: cytokine release syndrome [CRS]/hemophagocytic lymphohistiocytosis, neurotoxicity, respiratory failure, sepsis, septic shock, pneumonia, lung abscess, and acute myelogenous leukemia), and 2 of which were caused by progressive disease. CRS was experienced by a total of 94.8% of patients (grade 3/4: 4.1%), 90.7% experienced neutropenia (all grade 3/4), 81.4% experienced anemia (grade 3/4: 68.0%), and 79.4% experienced thrombocytopenia (grade 3/4: 59.8%). Median time to onset of CRS and duration were 7.0 days and 4.0 days, respectively. A total of 20.6% of patients experienced neurotoxicity due to CAR T-cell therapy (grade 3/4: 10.3%). At 14 days, maximum peripheral expansion of cilta-cel CAR+ T-cells was observed; 67% of patients with individual follow-up at 6 months had cilta-cel CAR+ T-cells below the level of quantification (2 cells/µL) in peripheral blood.
The phase 1b/2 CARTITUDE-1 preliminary study results show early, deep, and durable responses with a single low-dose infusion of cilta-cel in patients heavily pretreated with RRMM and a safety profile 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.