Ciltacabtagene autoleucel (cilta-cel), a chimeric antigen receptor (CAR) T-cell therapy directed against 2 discrete B-cell maturation antigen (BCMA) epitopes to increase binding strength, was previously shown in a phase 1 study to induce deep, durable responses with manageable toxicity in patients with relapsed/refractory multiple myeloma (RRMM). Updated data from the phase 1b portion of CARTITUDE-1, which is 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 to be used in the phase 2 investigation, and the primary objective of the phase 2 portion was to evaluate efficacy.
Eligible adults had measurable disease, Eastern Cooperative Oncology Group performance status ≤1, had received ≥3 prior regimens or were double refractory to a proteasome inhibitor and an immunomodulatory drug, and had received an anti-CD38 antibody. Bridging therapy was allowed following apheresis. 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.
At the time of the latest data cutoff, 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. The median age 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 was 8.8 months.
The observed overall response rate was 96.9%, with a stringent complete response rate of 67%, a very good partial response rate of 25.8%, and a partial response rate of 4.1%. A reduction in M protein was achieved in all patients. The median time to first response was 1.0 month, and the median time to complete response or better was 1.8 months, with responses deepening over time. The median duration of response was not reached by data cutoff. Of 57 patients evaluable for minimal residual disease (MRD), 93% were MRD negative at 10–5. The 12-month progression-free survival (PFS) rate (landmark) was 76.6%, and the median PFS has not been reached. The 12-month overall survival (OS) rate was 88.5%, and the median OS has also not been reached.
Fourteen deaths were reported in the study, 9 of which resulted from adverse events (n = 1 for all the following: cytokine release syndrome [CRS]/hemophagocytic lymphohistiocytosis, neurotoxicity, respiratory failure, pneumonia, and lung abscess; n = 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 cilta-cel CAR+ T-cells was observed at 14 days, and 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.
Preliminary results from the phase 1b/2 CARTITUDE-1 study reveal early, deep, and durable responses, as well as a safety profile consistent with prior studies, with a single low-dose infusion of cilta-cel in heavily pretreated patients with RRMM. 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.