Ide-Cel Receives EU Approval for Triple Class–Exposed R/R Multiple Myeloma

The European Commission has expanded its approval of idecabtagene autoleucel (ide-cel; Abecma) to include the treatment of adult patients with relapsed/refractory multiple myeloma who have received at least 2 prior therapies, including a proteasome inhibitor (PI), an immunomodulatory drug (IMiD), and an anti-CD38 antibody, and who have progressed on their last line of therapy. Ide-cel is the first CAR T-cell therapy to gain approval in the European Union (EU) in earlier lines of therapy for patients with triple class–exposed relapsed/refractory multiple myeloma. Along with this regulatory decision, ide-cel has maintained its orphan drug designation in the EU for patients with multiple myeloma.¹

The regulatory decision was supported by findings from the pivotal, open-label, global, phase 3 KarMMa-3 trial (NCT03651128), which evaluated ide-cel vs standard combination regimens in patients with triple class–exposed relapsed/refractory multiple myeloma, defined as those who had received 2 to 4 prior lines of therapy, including an PI, an IMiD, and an anti-CD38 monoclonal antibody. At a prespecified interim analysis with a median follow-up of 18.6 months, patients who received ide-cel (n = 254) experienced a median progression-free survival of 13.8 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.8) in those who received a standard combination regimen (n = 132; HR, 0.49; 95% CI, 0.38-0.63; P < .0001), which translated to a 51% reduction in the risk of disease progression or death with ide-cel.

“As patients with multiple myeloma become exposed to the 3 main classes of therapy earlier in treatment and still experience relapsed and/or refractory disease, it is critical that we continue to add innovative treatment options to our arsenal that can potentially provide long-term disease control,” Paula Rodriguez-Otero, MD, PhD, of the Department of Hematology at Clinica Universidad de Navarra in Pamplona, Spain, stated in a press release. “This expanded approval of ide-cel represents key progress in bringing a personalized therapy that delivers significantly improved, durable outcomes to patients with triple-class exposed relapsed and refractory multiple myeloma after 2 prior therapies.”

The findings from the interim analysis of KarMMa-3 were consistent with those from the primary analysis, which had the longest median follow-up for a randomized phase 3 CAR T-cell therapy trial in this patient population at 30.9 months. The overall response rate (ORR) with ide-cel was 71.3% (95% CI, 65.7%-76.8%), and the complete response (CR)/stringent CR (sCR) rate was 43.7%. Conversely, in the standard combination arm, the ORR was 42.4% (95% CI, 34%-50.9%), and the CR/sCR rate was 5.3%.

The median overall survival (OS) was 41.4 months (95% CI, 30.9-NR) with ide-cel vs 37.9 months (95% CI, 23.4-NR) with standard regimens (HR, 1.01; 95% CI, 0.73-1.40). Notably, patients on the control arm of KarMMa-3 were allowed to cross over to the ide-cel arm upon confirmed disease progression, and 56% of these patients crossed over to receive the CAR T-cell therapy as a subsequent treatment. Real-world evidence demonstrated that the median OS for patients with triple class–exposed relapsed/refractory multiple myeloma was approximately 13 months, showing that crossover had a confounding effect on the median OS observed with standard regimens in KarMMa-3, according to the news release from Bristol Myers Squibb.

A pooled analysis of the KarMMa-3, phase 2 KarMMa (NCT03361748), and phase 1 CRB-401 (NCT02658929) trials showed that ide-cel had a consistent safety profile and was mostly associated with low-grade and transient instances of cytokine release syndrome (CRS) and neurotoxicity. A total of 84.6% of patients who received ide-cel in these trials experienced any-grade CRS, 5.1% of patients experienced grade 3 or higher CRS, and 0.7% of patients experienced fatal/grade 5 CRS. The median time to CRS onset was 1 day (range, 1-17), and the median duration of CRS was 4 days (range, 1-63).

Among patients who received ide-cel in the KarMMa-3 and KarMMa trials (n = 353), 16.1% experienced any-grade neurotoxicity, 3.1% experienced grade 3/4 neurotoxicity, and no instances of grade 5 neurotoxicity were reported. The median time to neurotoxicity onset was 3 days (range, 1-317), and the median neurotoxicity duration was 3 days (range, 1-252). Notably, no cases of Parkinsonism were reported.

“[This] approval in the EU marks an exciting milestone in our efforts to bring the transformative potential of cell therapies into earlier lines of treatment,” Monica Shaw, MD, senior vice president and head of European Markets at Bristol Myers Squibb, added in the press release. “[ide-cel] is an important treatment option for patients with triple-class–exposed relapsed and refractory multiple myeloma who have received at least 2 prior therapies and is leading the way toward a promising shift in the treatment paradigm.”

In the United States, ide-cel gained FDA approval in 2021 for the treatment of adult patients with triple class–exposed relapsed/refractory multiple myeloma who have received at least 4 prior lines of therapy.² Additionally, a supplemental biologics license application for ide-cel for patients with triple class–exposed relapsed/refractory multiple myeloma has been accepted for FDA review.³ On March 15, 2024, the FDA’s Oncologic Drugs Advisory Committee voted in favor of ide-cel’s risk/benefit profile for patients with triple class–exposed relapsed/refractory multiple myeloma, based on data from KarMMA-3.⁴

Ide-cel was also approved in Great Britain and Israel for the treatment of adult patients with triple class–exposed relapsed/refractory multiple myeloma who have received at least 3 prior lines of therapy.¹ Furthermore, Ide-cel was the first cell therapy to be approved in Switzerland for adult patients with relapsed/refractory multiple myeloma who have received 2 or more prior lines of therapy, and it was the first cell therapy to be approved in Japan for the treatment of adult patients with triple class–exposed relapsed/refractory multiple myeloma who have received 2 prior lines of therapy.

References

1. Bristol Myers Squibb’s Abecma (idecabtagene vicleucel) becomes first CAR T cell therapy approved in the European Union in earlier lines for triple-class exposed relapsed and refractory multiple myeloma. News release. Bristol Myers Squibb. March 20, 2024. Accessed March 21, 2024. https://news.bms.com/news/corporate-financial/2024/Bristol-Myers-Squibbs-Abecma-idecabtagene-vicleucel-Becomes-First-CAR-T-Cell-Therapy-Approved-in-the-European-Union-in-Earlier-Lines-for-Triple-Class-Exposed-Relapsed-and-Refractory-Multiple-Myeloma/default.aspx
2. U.S. Food and Drug Administration approves Bristol Myers Squibb’s and bluebird bio’s Abecma (idecabtagene vicleucel), 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 21, 2024. https://bwnews.pr/39jWjjd
3. 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 March 21, 2024. https://news.bms.com/news/details/2023/
4. March 15, 2024, Meeting of the Oncologic Drugs Advisory Committee (ODAC). FDA. https://www.youtube.com/watch?v=VSjdGeeXb40