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MAY 13, 2020: “Bristol Myers Squibb and bluebird bio announced updated results from the pivotal, Phase 2 KarMMa study evaluating the efficacy and safety of the companies’ investigational B-cell maturation antigen (BCMA)-directed chimeric antigen receptor (CAR) T cell immunotherapy, idecabtagene vicleucel (ide-cel; bb2121), in patients with relapsed and refractory multiple myeloma.
These data will be shared in an oral presentation at the American Society of Clinical Oncology 2020 (ASCO20) Virtual Scientific Program on May 29 at 8:00 AM ET.
In the study, 128 patients with heavily pretreated relapsed and refractory multiple myeloma who were exposed to at least three prior therapies and were refractory to their last regimen per the International Myeloma Working Group (IMWG) definition (no response to therapy or disease progressed within 60 days) were treated with ide-cel across target dose levels of 150-450 x 106 CAR+ T cells.
Patients had a median of six prior regimens; 84% were refractory to all three classes of commonly used treatments including an immunomodulatory (IMiD) agent, a proteasome inhibitor (PI) and an anti-CD38 antibody, and 94% were refractory to anti-CD38 antibodies.
Median duration of follow-up was 13.3 months.
The overall response rate (ORR) was 73% across all dose levels, including 33% of patients who had a complete response (CR) or stringent CR (sCR).
Median duration of response (DoR) was 10.7 months, with 19.0 month median DoR for patients who had a CR or sCR.
Median progression-free survival (PFS) was 8.8 months, with 20.2 month median PFS for patients who had a CR or sCR.
All patients who had CR or sCR and were evaluable for minimal residual disease (MRD), were MRD-negative. Clinically meaningful benefit was consistently observed across subgroups, and nearly all subgroups had an ORR of 50% or greater, including older and high-risk patients.
The overall survival (OS) data continue to mature, with an estimated median OS of 19.4 months across all dose levels and 78% of patients alive at 12 months. Results support a favorable benefit-risk profile for ide-cel across the target dose levels of 150 to 450 × 106 CAR+ T cells.
The most frequently reported adverse events (AEs) were cytopenia and cytokine release syndrome (CRS). Cytopenias were common and not dose related.
Overall, CRS of any grade was reported in 84% (107/128) of patients. Grade 3 or higher CRS occurred in <6% (7/128) of patients, with one fatal CRS event. Investigator identified neurotoxicity events (iiNT) were reported in 18% (23/128) of patients, including Grade 3 iiNT reported in 3% (4/128) of patients. There were no Grade 4 or Grade 5 iiNT events reported.
“We are very encouraged and excited by the depth and durability of responses seen with ide-cel in this first pivotal study of a CAR T cell therapy in multiple myeloma.
Patients with relapsed and refractory multiple myeloma have decreased life expectancy, with no clear standard of care and limited responses to currently available treatment options, leaving them in critical need of new therapies,” said Nikhil C. Munshi, M.D., presenting author, Associate Director, The Jerome Lipper Multiple Myeloma Center at the Dana-Farber Cancer Institute, Boston, Massachusetts.
“The hematology and oncology community looks forward to the potential application of ide-cel in future clinical practice.”
“These longer-term results from the KarMMa study further demonstrate the clinical benefit of ide-cel and support its role as a potentially important therapeutic option for patients with triple-class exposed, relapsed and refractory multiple myeloma,” said Kristen Hege, M.D., senior vice president, Hematology/Oncology and Cell Therapy, Early Clinical Development, Bristol Myers Squibb.
“BMS and bluebird bio remain focused on improving outcomes in this population and bringing ide-cel to patients as quickly as possible.”
“Patients in the KarMMa study reflect a very advanced and highly refractory population, so it is particularly gratifying that the results announced today from the pivotal KarMMa study, demonstrating deep and durable responses, underscore the potential of ide-cel as a meaningful new treatment option for these patients,” said David Davidson, M.D., Chief Medical Officer, bluebird bio.
“bluebird bio, together with our partners at Bristol Myers Squibb, understands the urgency to deliver new therapeutic options for patients living with relapsed and refractory multiple myeloma, and we are committed to bringing this potentially first-in-class BCMA-directed CAR T cell therapy to patients in need.”
Ide-cel is not approved for any indication in any geography.
Ide-cel
Ide-cel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T cell immunotherapy.
The ide-cel CAR is comprised of a murine extracellular single-chain variable fragment (scFv) specific for recognizing BCMA, attached to a human CD8 α hinge and transmembrane domain fused to the T cell cytoplasmic signaling domains of CD137 4-1BB and CD3-ζ chain, in tandem. Ide-cel recognizes and binds to BCMA on the surface of multiple myeloma cells leading to CAR T cell proliferation, cytokine secretion, and subsequent cytolytic killing of BCMA-expressing cells.
Bristol Myers Squibb and bluebird bio’s broad clinical development program for ide-cel includes clinical studies (KarMMa-2, KarMMa-3, KarMMa-4) in earlier lines of treatment for patients with multiple myeloma, including newly diagnosed multiple myeloma. For more information visit clinicaltrials.gov.
Ide-cel is being developed as part of a Co-Development, Co-Promotion and Profit Share Agreement between Bristol Myers Squibb and bluebird bio.
KarMMa
KarMMa (NCT03361748) is a pivotal, open-label, single-arm, multicenter, multinational, Phase 2 study evaluating the efficacy and safety of ide-cel in adults 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.
The complete response rate is a key secondary endpoint. Other efficacy endpoints include time to response, duration of response, progression-free survival, overall survival, minimal residual disease evaluated by Next-Generation Sequencing (NGS) assay and safety.
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 lympho depleting chemotherapy.
All enrolled patients had received at least three prior treatment regimens, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 antibody, and were refractory to their last regimen, defined as progression during or within 60 days of their last therapy.“
