Ide-Cel Shows Benefit in Earlier Use in R/R Multiple Myeloma

Idecabtagene vicleucel (ide-cel; Abecma; Bristol Myers Squibb; 2seventy bio) significantly improved progression-free survival (PFS) in people with relapsed/refractory multiple myeloma (R/R MM) compared with standard regimens, according to updated data from the phase 3 KarMMa-3 trial (NCT03651128).¹

“Results from the KarMMa-3 study clearly demonstrate the clinical benefit of using a CAR T cell therapy earlier in the multiple myeloma treatment paradigm,” Anne Kerber, senior vice president and head, Cell Therapy Development, Bristol Myers Squibb, said in a statement.¹ “These data reinforce our commitment to unlocking the full potential of cell therapy as we strive to build on the company’s heritage of innovation in blood cancers and transform patients’ lives through science.”

The pivotal, randomized, multicenter, phase 3 KarMMA-3 trial is evaluating ide-cel in adults with MM that have relapsed after 2 to 4 prior lines of therapy and refractory to the last regimen. It is the first randomized clinical trial evaluating a chimeric antigen receptor (CAR) T-cell therapy in MM. Participants in the trial were randomized to treatment with ide-cel or combinations of daratumumab, pomalidomide, dexamethasone, bortezomib, ixazomib, lenalidomide, carfilzomib, or elotuzumab.

These new data, from a prespecified interim analysis, indicate that KarMMA-3 met its primary end point of statistically significantly improving PFS in treated study participants. The data also demonstrate an improvement in the trial's key secondary end point of overall response rate compared with standard regimens. Investigators continue follow-up to assess overall survival, another key secondary end point.

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“We are extremely pleased to have met the KarMMa-3 primary endpoint at an interim analysis. These results help to advance our efforts to make Abecma available for earlier lines of treatment for patients and we look forward to discussing these results with regulatory authorities,” Steve Bernstein, MD, chief medical officer, 2seventy bio, added to the statement.¹ “Today’s results are another important proof point for the transformative potential of autologous cell therapy and underscore the importance of continuing to study Abecma in earlier treatment settings for multiple myeloma.”

Ide-cel is the first BCMA-directed CAR T-cell therapy approved in the US for treating R/R MM after 4 or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The therapy is developed by Bristol Myers Squibb and 2seventy bio and was approved for this indication in March 2021. It is also approved in the European Union, Switzerland, Japan, Canada, and the United Kingdom in patients who have received at least 3 prior lines of therapy.

Safety data from KarMMA-3 were consistent with the safety profile seen in the pivotal KarMMA trial (NCT03361748), with no new safety signals. Further analyses of the data will be presented at an upcoming scientific meeting.

Further supporting ide-cel's efficacy, a recent comparison of health-related quality-of-life (HRQoL) scores presented at the European Hematology Association (EHA) 2022 Congress in June demonstrated that participants in KarMMA had higher HRQoL scores than those treated with belantamab mafodotin in the DREAMM-2 study (NCT03525678).² These data were presented by Nina Shah, MD, professor, Department of Medicine, University of California San Francisco.

REFERENCES

1. Bristol Myers Squibb and 2seventy bio announce topline results from KarMMa-3 Trial showing abecma (idecabtagenevicleucel) significantly improves progression-free survival versus standard regimens in relapsed and refractory multiple myeloma. News release. Bristol Myers Squibb. August 10, 2022. https://news.bms.com/news/corporate-financial/2022/Bristol-Myers-Squibb-and-2seventy-bio-Announce-Topline-Results-from-KarMMa-3-Trial-Showing-Abecma-idecabtagene-vicleucel-Significantly-Improves-Progression-Free-Survival-Versus-Standard-Regimens-in-Relapsed-and-Refractory-Multiple-Myeloma/default.aspx
2. U.S. Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagenevicleucel), the first anti-BCMA CAR T cell therapy for relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb and bluebird bio. March 26, 2021. Accessed March 26, 2021. https://bwnews.pr/39jWjjd
3. Shah N, Ayers D, Cope S, et al. Health-related quality of life in patients with relapsed/refractory multiple myeloma (RRMM) treated with idecabtagenevicleucel vs belantamabmafodotin: A matching-adjusted indirect comparison study. Presented at: EHA 2022 Congress, June 9-12, Vienna, Austria and virtually. Poster #P170