BMS and bluebird bio present data highlighting anti-BCMA CAR T Cell therapy, ide-cel, in relapsed and refractory multiple myeloma at ASH 2020.

Bristol Myers Squibb and bluebird bio, Inc. announced updated data evaluating the companies’ investigational B-cell maturation antigen (BCMA) directed chimeric antigen receptor (CAR) T cell therapy, idecabtagene vicleucel (ide-cel) , were presented at the 62nd American Society of Hematology (ASH) Annual Meeting and Exposition. The data include longer-term updated results from the original Phase 1 CRB-401 study of ide-cel in relapsed and refractory multiple myeloma (RRMM), including the primary endpoint of safety and exploratory endpoints of progression-free survival (PFS) and overall survival (OS). Analyses of the pivotal registrational KarMMa trial will also be presented at the ASH meeting, including an analysis of health-related quality of life in patients with RRMM treated with ide-cel, and a subgroup analysis of outcomes for patients with high-risk RRMM. A subgroup analysis of elderly patients with RRMM treated with ide-cel in the KarMMa study were presented today. In addition, data from the ongoing Phase 1 CRB-402 study of bb21217, an investigational BCMA-directed CAR T cell therapy, were presented at the meeting. Updated Results from CRB-401 Study of Ide-cel: In the Phase 1 CRB-401 study, 62 patients with heavily pretreated relapsed and refractory multiple myeloma were treated with ide-cel across dose levels of 50, 150, 450, or 800 × 106 CAR positive T cells (Presentation #131). The primary endpoint was safety, and secondary and exploratory endpoints included response rates, PFS, OS, and minimal residual disease (MRD). Safety remained consistent with previously reported results from CRB-401. The most frequent adverse events (AEs) were neutropenia (92%), cytokine release syndrome (CRS; 76%), anemia (76%), and thrombocytopenia (74%). The most frequent Grade 3/4 AEs were neutropenia (89%), leukopenia (61%), anemia (57%), and thrombocytopenia (57%). Most CRS events were Grade 1 or 2. Four patients (7%) had Grade 3 CRS; there were no Grade 4 or 5 CRS events reported. Among 62 patients treated with ide-cel in this study, the overall response rate (ORR) was 76%, including 24 patients (39%) who achieved a complete response (CR). The median duration of response (DoR) was 10.3 months. Median PFS was 8.8 months and median OS was 34.2 months, with a median follow-up of 14.7 months. Full results from the CRB-401 study will be presented in an oral presentation (Presentation #131). Analyses of Pivotal KarMMa Study: Subgroup Analyses of Ide-cel Outcomes in High-Risk and Elderly Patients and Health-Related Quality of Life : Ide-cel demonstrated deep and durable responses in the pivotal Phase II KarMMa study of patients with triple-class exposed relapsed and refractory multiple myeloma. A subgroup analysis was conducted to assess outcomes of treatment with ide-cel across target dose levels of 150 to 450 × 106 CAR positive T cells in patients with poor prognosis, including those with extramedullary disease, high-risk cytogenetics, and high tumor burden. In the analysis of 128 patients, ide-cel demonstrated deep and durable responses across the majority of subgroups, including those with the highest risk. The ORR and CR rate were ?65% and ?20%, respectively, for the majority of high-risk subgroups. Additionally, in the majority of the high-risk subgroups, the median DoR was >9.2 months and the median PFS was >7.5 months. Results will be presented in a poster presentation on Monday, December 7 (Presentation #3234). A separate subgroup analysis was conducted to evaluate the outcomes of treatment with ide-cel in elderly patients (Presentation #1367). Multiple myeloma occurs most commonly among the older population, with a median age of 69 at diagnosis. Advanced age has been shown to negatively affect prognosis and limit treatment options. Of the 128 patients treated with ide-cel in the KarMMa study, 45 patients (35%) were aged greater than 65 years and 20 patients (16%) were aged greater than 70 years. Response rates for both age groups were comparable and consistent with the overall ide-cel treated population, across all target dose levels, with ORRs of 84% to 90% and CR rates of 31% to 35%. Likewise, median DoR among responders in both age groups (10.7 months in patients aged greater than 65 years and 11.0 months in patients aged greater than 70 years) was similar to that of the overall ide-cel treated population. Median PFS was 8.6 months (95% CI, 4.9-12.2) in patients aged greater than 65 years and 10.2 months (95% CI, 3.1-12.3) in patients aged greater than 70 years. Additionally, no new safety signals were observed. In an analysis of the impact of ide-cel treatment on health-related quality of life (HRQoL) measures in patients with relapsed and refractory multiple myeloma from the KarMMa study, ide-cel was associated with clinically meaningful QoL benefits without compromising any HRQoL domains (Presentation #437). Patients demonstrated a clinically meaningful improvement in most functioning and symptom scores from baseline to Month 3 through 15, with statistical significance (p<0.05) reached at various time points for different subscales throughout the follow-up period. full results from the hrqol analysis will be presented tomorrow sunday december 6 in an oral presentation presentation 437. phase 1 crb-402 study of bb 21217 :updated safety and efficacy results from the ongoing phase 1 study crb-402 of bb21217 an investigational bcma-directed car t cell therapy being studied in patients with relapsed and refractory multiple myeloma were also presented in an oral presentation presentation 130. bb 21217 uses the ide-cel car molecule and is cultured with the pi3 kinase inhibitor bb007 to enrich for t cells displaying a memory-like phenotype with the intention of increasing the in vivo persistence of car t cells. as of the september 1 2020 cutoff date 69 patients were treated with bb 21217 and updated results include new data following the introduction of a manufacturing process change. the study has completed enrollment and follow-up is ongoing as data continue to mature and the durability of response at the rp2d is assessed.>