Abecma reduced the risk of disease progression or death by 51% versus standard regimens in earlier lines of therapy in KarMMa-3 study for r/r multiple myeloma. BMS.
Bristol Myers Squibb and 2seventy bio, Inc. announced the first publication and presentation of positive results from KarMMa-3, a pivotal Phase III, open-label, global, randomized, controlled study evaluating Abecma (idecabtagene vicleucel) compared with standard combination regimens in adults with relapsed and refractory multiple myeloma after two to four prior lines of therapy , including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, and who were refractory to their last regimen.
Data from KarMMa-3 are being published in The New England Journal of Medicine and simultaneously presented at the EBMT and the European Hematology Association’s (EHA) 5th European CAR T-cell Meeting on Friday, February 10 in an oral presentation during the Best Abstract Session.
At a median follow up of 18.6 months, treatment with Abecma (n=254)demonstrated a clinically meaningful and statistically significant improvement in the primary endpoint of progression-free survival (PFS) compared with standard regimens (n=132), with a median PFS of 13.3 months (95% CI: 11.8-16.1) vs. 4.4 months (95% CI: 3.4-5.9), respectively (HR:0.49; p<0.0001). this represents a 51% reduction in risk of disease progression or death with abecma. based on results from karmma-3, abecma is the first and only chimeric antigen receptor (car) t cell therapy to demonstrate superiority over standard regimens in triple-class exposed relapsed and refractory multiple myeloma in a randomized, controlled phase iii trial.></0.0001).>
“In earlier lines of treatment for multiple myeloma, regimens consisting of immunomodulatory agents, proteasome inhibitors, and anti-CD38 monoclonal antibodies are often used to help manage the disease. This shift in the treatment paradigm leaves many patients who are triple-class exposed with relapsed and refractory disease and in need of new treatment options sooner,” said Paula Rodriguez-Otero, M.D., Ph.D., Department of Hematology, Clinica Universidad de Navarra, Pamplona, Spain. “Results from the KarMMa-3 study with Abecma clearly demonstrate the benefit of earlier use of a CAR T cell therapy in providing the longest progression-free survival for patients with relapsed and refractory multiple myeloma compared to current standard regimens for these patients.”
Results for the key secondary endpoint of overall response rate also met statistical significance with the majority of patients (71%) treated with Abecma achieving a response, and 39% achieving a complete response or stringent complete response. In comparison, less than half of patients (41%) who received standard regimens achieved a response, with 5% experiencing a complete response or stringent complete response (p<0.0001). responses with abecma were durable with a median duration of 14.8 months (95% ci: 12.0-18.6) compared with 9.7 months (95% ci: 5.4-16.3) for standard regimens. clinical benefit with abecma was consistently observed across difficult-to-treat subgroups.></0.0001).>
“For relapsing triple-class exposed multiple myeloma patients, median progression-free survival is just 4.6 months and there is no established standard treatment approach that provides durable responses,” said Sergio Giralt, M.D., Division of Hematologic Malignancies, Memorial Sloan Kettering Cancer Center. “In this study, we are seeing efficacy among a population with historically difficult-to-treat disease, with a significant improvement in progression-free survival and deep and lasting responses. These results from KarMMa-3 introduce the potential for this anti-BCMA CAR T cell therapy to become a standard of care earlier in the treatment course for relapsed and refractory multiple myeloma.”.
Abecma exhibited a consistent and generally predictable safety profile, including no new safety signals, with mostly low-grade occurrences of cytokine release syndrome (CRS) and neurotoxicity. In patients treated with Abecma, 88% experienced any grade CRS, with Grade 3/4 events occurring in 4% of patients. Two patients (1%) experienced a Grade 5 CRS event. Median time to onset of CRS was 1 day (range: 1-14) and median duration of CRS was 3.5 days (range: 1-51). Any grade neurotoxicity occurred in 15% of patients, with Grade 3/4 neurotoxicity occurring in 3% of patients, and no Grade 5 events reported. Median time to onset of neurotoxicity was 3 days (range: 1-317) and median duration of neurotoxicity was 2 days (range: 1-37)..
Bristol Myers Squibb and 2seventy bio intend to include these data in a planned supplemental Biologics License Application submission to the FDA in 2023.
Abecma is the first-in-class B-cell maturation antigen (BCMA)-directed CAR T cell immunotherapy approved by the FDA for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.
"Ide-cel or Standard Regimens in Relapsed and Refractory Multiple Myeloma"; Paula Rodriguez-Otero, M.D., Ph.D., Sikander Ailawadhi, M.D., Bertrand Arnulf, M.D., Ph.D., Krina Patel, M.D., et al.February 10, 2023. DOI: 10.1056/NEJMoa2213614.
Learning Zones
The Learning Zones are an educational resource for healthcare professionals that provide medical information on the epidemiology, pathophysiology and burden of disease, as well as diagnostic techniques and treatment regimens.
1 mins