In patients with relapsed/refractory multiple myeloma (RRMM) at target dose levels of ≥150 × 106 chimeric antigen receptor (CAR)+ T-cells, the updated analysis of the phase 1 CRB-401 study supports a favorable clinical benefit–risk profile for the B-cell maturation antigen (BCMA)-directed CAR T-cell therapy, idecabtagene vicleucel.
CRB-401 is a phase 1 study in which the efficacy and tolerability of idecabtagene vicleucel (ide-cel), a BCMA-directed CAR T-cell therapy, is evaluated in patients with RRMM. Primary end point was safety; secondary end points included tumor response based on the International Myeloma Working Group criteria. Exploratory end points included progression-free survival, overall survival (OS), and minimal residual disease (MRD). Although favorable phase 1 and 2 data have been published for 62 patients who continued therapy in this ongoing study, updated efficacy and safety data are now available.
Patients who had received ≥3 prior lines of therapy were enrolled in the expansion phase of this 2-part dose-escalation and dose-expansion study, including a proteasome inhibitor, an immunomodulatory drug, and an anti-CD38 antibody, and who were refractory to their last line of therapy. First, for 3 days, patients completed lymphodepletion with fludarabine and cyclophosphamide and then rested for 2 days. Subsequently, in the dose-escalation phase, ide-cel was administered at target doses of 50, 150, 450, or 800 × 106 CAR+ T-cells. In the dose-expansion phase, ide-cel was administered at target doses of 150 to 450 × 106 CAR+ T-cells.
Through January 14, 2020, the current updated analysis includes 21 and 41 patients who received ide-cel in the dose-escalation and dose-expansion phases, respectively. A total of 45% of patients (28/62) received >6 prior regimens, and 90% and 77% were previously exposed to, or refractory to, daratumumab, respectively. Patient median study age was 61 years and observed in 44% of patients was high tumor burden, defined as ≥50% bone marrow CD138+ plasma cells. At data cutoff, 49 of 62 patients (79%) discontinued the study, primarily because of progressive disease (58%), patient withdrawal (10%), and death (10%).
Regarding adverse events (AEs), 92% of patients experienced neutropenia, 76% developed cytokine release syndrome (CRS), whereas 76% and 74% experienced anemia and thrombocytopenia, respectively. Among grade 3/4 AEs, neutropenia, leukopenia, anemia, and thrombocytopenia were the most common and observed in 89%, 61%, 57%, and 57% of patients, respectively. Most CRS events were grade 1/2, with only 4 (7%) patients experiencing grade 3 CRS, the incidence of which generally increased with higher doses. Twenty-seven (44%) patients experienced neurologic AEs, the majority of which were grade 1 (grade 3 and 4 events were each recorded in 1 patient).
In this updated analysis, overall response rate was 76% (47/62); 39% of patients (24/62) achieved complete response or better and 65% of patients (40/62) achieved a very good partial response or better. Median duration of response was 10.3 months. A total of 30/37 responders evaluable for MRD status were MRD-negative, defined as ≤10 nucleated cells, at ≥1 time points, whereas the remainder of patients were MRD-positive. For all 62 patients, median PFS, median OS, and median follow-up rates were 8.8 months, 34.2 months, and 14.7 months, respectively. Clinical benefit appeared to be dose-dependent; higher response rates and better survival outcomes were observed for patients who received ≥150 × 106 CAR+ T-cells.
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.
The updated analysis results 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.
