Ide-Cel Wins Japanese Approval in Early Relapsed/Refractory Multiple Myeloma

Makoto Sugita

The BCMA-directed CAR T-cell therapy idecabtagene vicleucel (ide-cel; Abecma) has received marketing and manufacturing approval in Japan for its supplemental new drug application (sBLA) in patients with relapsed/refractory multiple myeloma who have received at least 2 prior lines of therapy, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.¹

The approval is based on findings from the pivotal, phase 3 KarMMA-3 trial (NCT03651128) in which ide-cel led to a median progression-free survival (PFS) of 13.3 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.9) with standard therapy (HR, 0.493; 95% CI, 0.377-0.645; P < .0001). Additionally, ide-cel led to improved objective responses, at 71.3% vs 41.7% with standard therapy (OR, 3.54; 95% CI, 2.26-5.54; P < .0001).^1,2

“Multiple myeloma is an intractable disease with recurrent relapses that are difficult to cure with existing therapies. Treatment options for patients with relapsed/refractory multiple myeloma are limited, and we are pleased that [idecabtagene vicleucel] is the first CAR T-cell therapy to be approved for earlier use as a treatment option to address the unmet needs of these patients. We remain committed to researching and developing innovative therapies to transform patient lives with serious diseases through science,” Makoto Sugita, head of R&D at Bristol Myers Squibb Japan, stated in a news release.

The agent is also approved in Japan for use in patients with relapsed/refractory multiple myeloma who have received at least 3 prior lines of therapy, including an IMiD, PI, and anti-CD38 antibody.³

In April 2023, the FDA accepted a sBLA seeking the approval of ide-cel for the treatment of adult patients with triple-class exposed, relapsed/refractory multiple myeloma based on data from KarMMa-3.⁴ The FDA assigned a target action date of December 16, 2023, under the Prescription Drug User Fee Act.

The global, open-label, randomized, phase 3 KarMMA-3 trial enrolled patients with relapsed/refractory multiple myeloma following treatment with 2 to 4 prior lines of therapy, including an IMiD, PI, and daratumumab (Darzalex). A total of 386 patients including 9 Japanese patients were randomly assigned to receive ide-cel or standard treatment regimens including daratumumab, pomalidomide (Pomalyst), and dexamethasone; daratumumab, bortezomib (Velcade), and dexamethasone; ixazomib (Ninlaro), lenalidomide (Revlimid), and dexamethasone; carfilzomib (Kyprolis) and dexamethasone; or elotuzumab (Empliciti), pomalidomide, and dexamethasone.¹

PFS served as the primary end point of the study, with secondary end points of objective response rate and overall survival.

At the data cutoff of April 18, 2022, with median follow-up of 18.6 months (range, 0.4-35.4), the 6- and 12-month PFS rates with ide-cel were 73% and 55%, respectively, vs 40% and 30% with standard treatment. Moreover, the PFS benefit with ide-cel was seen regardless of age, race, number of previous regimens, or presence or absence of high-risk cytogenetic abnormalities, extramedullary disease, high tumor burden, or triple-class–refractory status.²

At the 2023 ASH Annual Meeting, investigators presented health-related quality of life (HRQoL) data from the trial, indicating that ide-cel also led to a significant and meaningful improvement in multiple myeloma–relevant symptoms, functioning, and overall health status/HRQoL compared with standard treatment reigmens.⁵

References

1. Bristol Myers Squibb’s Abecma becomes first CAR T approved for use in earlier lines of therapy for patients with relapsed or refractory multiple myeloma in Japan. News release. Bristol-Myers Squibb K.K. December 6, 2023. Accessed December 14, 2023. https://news.bms.com/news/details/2023/Bristol-Myers-Squibbs-Abecma-Becomes-First-CAR-T-Approved-for-Use-in-Earlier-Lines-of-Therapy-for-Patients-with-Relapsed-or-Refractory-Multiple-Myeloma-in-Japan/default.aspx
2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed and refractory multiple myeloma. N Engl J Med. 2023;388(11):1002-1014. doi:10.1056/NEJMoa2213614
3. Bristol Myers Squibb receives approval for Abecma (idecabtagene vicleucel), the first CAR T therapy approved for the treatment of multiple myeloma in Japan. News release. Bristol Myers Squibb. January 20, 2022. Accessed December 14, 2023. https://news.bms.com/news/details/2022/Bristol-Myers-Squibb-Receives-Approval-for-Abecma-idecabtagene-vicleucel-the-First-CAR-T-Therapy-Approved-for-the-Treatment-of-Multiple-Myeloma-in-Japan/default.aspx
4. Regulatory applications accepted across three regions globally for Abecma for earlier use in adults with triple-class exposed relapsed and/or refractory multiple myeloma. News release. Bristol Myers Squibb. April 17, 2023. Accessed December 14, 2023. https://news.bms.com/news/details/2023/Regulatory-Applications-Accepted-Across-Three-Regions-Globally-for-Abecma-for-Earlier-Use-in-Adults-with-Triple-Class-Exposed-Relapsed-andor-Refractory-Multiple-Myeloma/default.aspx
5. Delforge M, Patel KK, Eliason L, et al. Effects of idecabtagene vicleucel (ide-cel) versus standard regimens on health-related quality of life (HRQoL) in patients with relapsed/refractory multiple myeloma (RRMM) who had received 2-4 prior regimens: updated results from the phase 3 KarMMA-3 trial. Blood. 2023;142(suppl 1):96. doi:10.1182/blood-2023-179152