Ide-Cel Earns European Approval in Triple-Class Exposed Multiple Myeloma

“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," according to Paula Rodriguez-Otero, MD, PhD.

The European Commission has granted approval to idecabtagene vicleucel (ide-cel; Abecma) as a treatment for adult patients with relapsed/refractory multiple myeloma, according to a press release from Bristol Myers Squibb, the developers of the agent.¹

Specifically, ide-cel is indicated for patients who have received a minimum of 2 prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 antibody.

Supporting data for the approval in this indication came from the phase 3 KarMMa-3 trial (NCT03651128) assessing ide-cel vs standard of care in those with relapsed/refractory multiple myeloma previously treated with 2 to 4 prior lines of treatment.

With a median follow-up of 18.6 months at the time of the pre-specified interim analysis, the median progression-free survival (PFS) with ide-cel was 13.8 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.8) in those who received standard treatment (HR, 0.49; 95% CI, 0.38-0.63; P <.0001). Additionally, the overall response rate (ORR) with ide-cel was 71.3% (95% CI, 65.7%-76.8%), which included a complete response (CR) or stringent CR in 43.7% of patients. The ORR with standard treatments was 42.4% (95% CI, 34.0%-50.9%), with 5.3% of patients achieving a CR or stringent CR.

Based on a pooled analysis of findings from the KarMMa-3 trial, the KarMMa trial (NCT03361748), and the phase 1 CRB-401 trial (NCT02658929), any-grade and grade 3 or higher cytokine release syndrome (CRS), respectively, affected 84.6% and 5.1% of patients who received ide-cel. In the KarMMa and KarMMa-3 trials, any-grade neurotoxicity was reported in 16.1% of patients who were treated with ide-cel, and grade 3/4 events affected 3.1%.

“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, Clinica Universidad de Navarra, Pamplona, Spain, said in the press release.¹ “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.”

In the KarMMa-3 trial, patients were assigned to receive ide-cel at a dose ranging from 150 to 450 x 10⁶ CAR-positive T cells following lymphodepleting chemotherapy or standard therapy.² Treatment options in the control arm included agents such as daratumumab (Darzalex), pomalidomide (Pomalyst), and dexamethasone.

The trial’s primary end point was PFS. Secondary end points included ORR, event-free survival, and overall survival.

The FDA previously approved ide-cel as a treatment for patients with relapsed/refractory multiple myeloma following 4 or more prior lines of therapy in March 2021.³ Supporting data for this approval came from the KarMMa study.

The FDA accepted a supplemental biologics license application (sBLA) for ide-cel as a treatment for patients with relapsed/refractory multiple myeloma previously treated with an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody in April 2023.⁴ Supporting data for the sBLA came from the KarMMa-3 study. In March 2024, the FDA Oncologic Drugs Advisory Committee (ODAC) cast an 8-to-3 vote in support of the use of ide-cel in this patient population.⁵

“I think the [PFS] is very convincing…Almost all of the progressions and early deaths were related to patients who had rapidly progressive disease and did not get the product [in time]. Overall, I was quite impressed by the PFS curves,” said Ranjana Advani, MD, a Saul A. Rosenberg, MD professor of Lymphoma at Stanford Medicine, said during the ODAC meeting.⁵

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://tinyurl.com/4cmdxxkt
2. Efficacy and safety study of bb2121 versus standard regimens in subjects with relapsed and refractory multiple myeloma (RRMM) (KarMMa-3). ClinicalTrials.gov. Accessed March 21, 2024. https://tinyurl.com/mrthvwk5
3. 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. Inc. March 26, 2021. Accessed March 21, 2024. https://tinyurl.com/9fkjh8u9
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 March 21, 2024. bit.ly/3ULmLZt
5. March 15, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live March 15, 2024. Accessed March 21, 2024. https://shorturl.at/fmxz7