CRB-401 is a phase 1 study evaluating the efficacy and tolerability of idecabtagene vicleucel (ide-cel), a B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T-cell therapy, in patients with relapsed and/or refractory multiple myeloma (RRMM). The primary end point was safety; secondary end points included tumor response based on the International Myeloma Working Group criteria; and exploratory end points included progression-free survival (PFS), overall survival (OS), and minimal residual disease (MRD). Although favorable phase 1 and 2 data have been published, updated efficacy and safety data are now available for 62 patients who continued therapy in this ongoing study.
The expansion phase of this 2-part dose-escalation and dose-expansion study enrolled patients who had received ≥3 prior lines of therapy, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, and who were refractory to their last line of therapy. First, patients completed lymphodepletion with fludarabine and cyclophosphamide for 3 days and then rested for 2 days. Subsequently, ide-cel was administered at target doses of 50, 150, 450, or 800 × 106 CAR+ T-cells in the dose-escalation phase and 150 to 450 × 106 CAR+ T-cells in the dose-expansion phase.
The current updated analysis through January 14, 2020, includes 21 and 41 patients who received ide-cel in the dose-escalation phase and dose-expansion phase, respectively. A total of 45% of patients (28/62) had received >6 prior regimens, and 90% and 77% had been previously exposed to, or were refractory to, daratumumab, respectively. The median age in the study was 61 years, and high tumor burden, defined as ≥50% bone marrow CD138+ plasma cells, was observed in 44% of patients. Six deaths occurred within 6 months, all attributed to myeloma.
Regarding adverse events (AEs), 92% of patients experienced neutropenia, 76% developed cytokine release syndrome (CRS), and 76% and 74% experienced anemia and thrombocytopenia, respectively. Among grade 3/4 AEs, neutropenia, leukopenia, anemia, and thrombocytopenia were the most common, observed in 89%, 61%, 57%, and 57% of patients, respectively. Most CRS was grade 1/2, with only 4 (7%) patients experiencing grade 3 CRS, the incidence of which generally increased with higher doses. Twenty-two (36%) patients experienced neurologic toxicity, the majority of which was grade 1 (1 grade 4 event was recorded).
The overall response rate in this updated analysis was 76%, with 39% of patients achieving complete response or better (≥CR), and 65% of patients achieving a very good partial response or better. Median duration of response was 10.3 months. All patients with ≥CR, with qualified assessment, were MRD negative. Median PFS was 8.8 months and median OS was 34.2 months for all 62 patients. Clinical benefit appeared to be dose-dependent, as higher response rates and better survival outcomes were observed for patients who received ≥150 × 106 CAR+ T-cells.
Results from this updated analysis of the CRB-401 study are consistent with previous reports showing deep and durable responses for heavily pretreated patients with RRMM who received ide-cel. A favorable clinical benefit–risk profile at target doses ≥150 × 106 CAR+ T-cells was observed.
Reference
Abstract 131. ASH 2020. December 5, 2020. Idecabtagene Vicleucel (ide-cel, bb2121), a BCMA-Directed CAR T-Cell Therapy, in Patients with Relapsed and Refractory Multiple Myeloma: Updated Results from Phase 1 CRB-401 Study.