BMS and bluebird bio announce positive top-line results from the pivotal phase II KarMMa study of Ide-cel in relapsed and refractory multiple myeloma

Bristol-Myers Squibb Company and bluebird bio, Inc.announced positive top-line results from KarMMa, a pivotal, open-label, single arm, multicenter, Phase II study of idecabtagene vicleucel (ide-cel; bb2121) KarMMa, which evaluated the efficacy and safety of the companies� lead investigational BCMA-targeted chimeric antigen receptor (CAR) T cell therapy candidate for patients with relapsed and refractory multiple myeloma, met its primary endpoint and key secondary endpoint.

KarMMa enrolled 140 patients, of whom 128 patients were treated with ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells. All treated patients were exposed to at least three prior therapies, including an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an anti-CD38 antibody, and all were refractory to their last regimen. Ninety-four percent of patients were refractory to an anti-CD38 antibody and 84% percent were triple refractory (refractory to an IMiD agent, PI and anti-CD38 antibody). The median follow-up duration for all subjects was 11.3 months.

KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multi-center phase II study evaluating the efficacy and safety of ide-cel in adult patients with relapsed and refractory multiple myeloma, in North America and Europe. The primary endpoint of the study is overall response rate as assessed by an independent review committee (IRC) according to the International Myeloma Working Group (IMWG) criteria. Complete response rate is a key secondary endpoint. Other efficacy endpoints include time to response, duration of response, progression-free survival, overall survival and minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay. The study enrolled 140 patients, of whom 128 received ide-cel across the target dose levels of 150-450 x 106 CAR+ T cells after receiving lymphodepleting chemotherapy. All enrolled patients had received at least three prior treatment regimens, including an IMiD agent, a PI and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.

Results: ORR 300 x 10 (n=70)= 48 (68.6).CR/sCR = 20 (28.6).Median DOR months = 9.9.Median PFS months = 5.8. ORR 450 x 10 (n = 54) = 44 (81.5). Cr/sCR = 19 (35.2).Median DOR months = 11.3. Median PFS months = 11.3. ORR 156 - 450 x 10 ( n =128) = 94 (73.4).Cr/sCR = 40 (31.3).Median DOR months = 10.6.Median PFS= 8.6.

Overall, the safety results were consistent with those observed in the phase 1 CRB-401 study, which evaluated the preliminary safety and efficacy of ide-cel. Instances of grade 3 or higher cytokine release syndrome (CRS) occurred in 5.5% (7/128) of patients, including one fatal CRS event. Investigator identified grade 3 or higher neurotoxicity events (iiNT) occurred in 3.1% (4/128) of patients and there were no Grade 4 iiNT events reported. Grade 3 or higher CRS and iiNT events were reported in <6% of subjects at each target dose. crs of any grade occurred in 83.6 107 128 of patients and iint of any grade occurred in 18 23 128 of patients.>