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Re: European Medicines Agency Validates Bristol Myers Squibb’s Applications for Idecabtagene Vicleucel (Ide-cel, bb2121) and CC-486 Dana Farber's Nikhil Munshi will be presenting the pivotal Ide-cel KarMMa results at ASCO2020. In conversation at ASCO2019, Dana Farber had a backlog of over 100 patients interested in Ide-cel as First-in-Class (F-I-C) BCMA Car-T therapy. ASCO2020 Ide-cel AbstractsIdecabtagene vicleucel (ide-cel; bb2121), a BCMA-targeted CAR T-cell therapy, in patients with relapsed and refractory multiple myeloma (RRMM): Initial KarMMa results.Add to Collection Authors:Nikhil C. Munshi, Larry D. Anderson, Jr, Nina Shah, Sundar Jagannath, Jesus G. Berdeja, Sagar Lonial, Noopur S. Raje, David Samuel DiCapua Siegel, Yi Lin, Albert Oriol, Philippe Moreau, Ibrahim Yakoub-Agha, Michel Delforge, Fabio Petrocca, Jamie Connarn, Payal Patel, Liping Huang, Timothy Brandon Campbell, Kristen Hege, Jesus San Miguel, on behalf of the KarMMa Study Investigators; Dana-Farber...Research Funding:Bristol-Myers Squibb and bluebird bioBackground:Outcomes are poor in triple-class exposed RRMM patients (pts) who progress on immunomodulatory agents (IMiDs), proteasome inhibitors (PIs), and CD38 antibodies (mAbs). Ide-cel, a BCMA targeted CAR T cell therapy, showed promising tolerability and efficacy in RRMM pts in the phase I CRB-401 study (NEJM2019;380:1726). We present primary efficacy and safety data from the pivotal phase II KarMMa trial of ide-cel in RRMM (NCT03361748).Methods:Enrolled pts had ≥3 prior regimens (including IMiD, PI, and CD38 mAb) and were refractory to their last regimen per IMWG criteria. After lymphodepletion (cyclophosphamide 300 mg/m2+ fludarabine 30 mg/m2 x 3), pts received 150─450 × 106 CAR+ T cells (target dose range). Endpoints included overall response rate (ORR; primary), complete response (CR) rate, duration of response (DoR), and PFS.Results:Of 140 pts enrolled, 128 received ide-cel. Median age was 61 y; median no. of prior regimens was 6; 84% were triple- and 26% were penta-refractory. Most pts (88%) had bridging therapy. At data cutoff (16 Oct 2019), median follow up was 11.3 mo. ORR was 73% and median PFS was 8.6 mo; both increased with higher dose (Table). All subgroups had an ORR ≥50%, including older and high-risk pts. Most common any-grade (Gr) toxicities were cytopenias (97%) and cytokine release syndrome (CRS; 84%). CRS was mainly Gr 1/2; 5 pts (5%) had Gr 3, 1 had Gr 4, and 1 had Gr 5 (at 300 × 106). Neurotoxicity developed in 23 pts (18%); 4 (3%) Gr 3 and 0 Gr ≥4. Median peak CAR+ T cell expansion occurred at 11 d. Expansion was higher in responders and parameters (AUC0−28d, Cmax) increased with higher dose, with exposure overlap across doses. Persistence was durable, with CAR+ T cells detected in 29/49 (59%) and 4/11 pts (36%) at 6 and 12 mo.Conclusions:Ide-cel demonstrated deep, durable responses in heavily pretreated RRMM pts. Efficacy and safety reflected prior reports and support a favorable ide-cel clinical benefit-risk profile across the target dose range. Clinical trial information: NCT03361748.
NT, investigator identified neurotoxicity; sCR, stringent CR. *Kaplan-Meier estimate. †Not reported due to small n. KarMMa-RW: A study of real-world treatment patterns in heavily pretreated patients with relapsed and refractory multiple myeloma (RRMM) and comparison of outcomes to KarMMa.Add to Collection Authors:Sundar Jagannath, Yi Lin, Hartmut Goldschmidt, Donna Ellen Reece, Ajay K. Nooka, Paula Rodríguez Otero, Kosei Matsue, Nina Shah, Larry D. Anderson, Jr, Kimberly Wilson, Arlene S. Swern, Faiza Zafar, Amit Balkrishna Agarwal, David Samuel DiCapua Siegel; Mount Sinai Medical Center, New York, NY; Mayo Clinic, Rochester, MN; University Hospital Heidelberg, Internal Medicine V and National Center...Research Funding:Bristol-Myers Squibb and bluebird bioBackground:RRMM patients (pts) triple-class exposed (to immunomodulatory drugs [IMiDs], proteasome inhibitors [PIs] and anti-CD38 monoclonal antibodies [mAbs]) have limited treatment (tx) options. The ongoing phase II KarMMa study (NCT03361748) is examining idecabtagene vicleucel (ide-cel; bb2121), a BCMA targeted CAR T cell therapy, in RRMM pts with ≥3 prior regimens (IMiD, PI and CD38 mAb inclusive) who are refractory to their last tx per IMWG criteria. This study aimed to 1) assess tx patterns and outcomes in real world (RW) RRMM pts similar to the KarMMa population and; 2) compare outcomes with SoC in a synthetic cohort vs ide-cel in KarMMa.Methods:In this global, noninterventional, retrospective study (KarMMa-RW), pt-level data from clinical sites, registries and databases were collated into a single data model. RW pts meeting KarMMa eligibility criteria (eligible cohort; EC) were compared with KarMMa (N = 128) using trimmed stabilized inverse probability of tx weighted propensity scores (IPTW PS) for pts in both studies with Poisson regression for ORR and ≥VGPR, and Cox models with study as a term for PFS. All models were adjusted for unbalanced covariates.Results:Of 1949 RW pts, 1171 were refractory to last regimen (median age, 68 y; median no. of prior regimens, 5; triple-class refractory, 41%). Further selection for subsequent tx, organ function and no comorbidities yielded 190 EC pts who had > 90 distinct tx regimens. With a median follow-up of 11.3 mo (KarMMa) and 10.2 mo (EC) at data cutoff (Oct 30, 2019), ORR, ≥VGPR and PFS were significantly improved in KarMMa vs EC (Table).Conclusions:Results from the KarMMa-RW study confirm that there is no clear SoC for heavily pretreated RW RRMM pts and responses are suboptimal with currently available therapies. Ide-cel showed deep, durable responses and significantly improved PFS in RRMM pts, representing a potential new tx option in RRMM. Clinical trial information: tbd.
HR, hazard ratio; RR, risk ratio *Across all target doses †Derived for both studies using trimmed stabilized IPTW PS ‡CR not reported due to missing biopsy data in EC to confirm CR |
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Msg # | Subject | Author | Recs | Date Posted |
2847 | Re: European Medicines Agency Validates Bristol Myers Squibb’s Applications for Idecabtagene Vicleucel (Ide-cel, bb2121) and CC-486 | Biotech2050 | 3 | 5/23/2020 11:39:06 AM |