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

News
Article

Data from the phase 3 KarMMa-3 trial support the approval of idecabtagene vicleucel for relapsed/refractory multiple myeloma in the European Union.

“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.

“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
Related Videos
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
A panel of 3 experts on multiple myeloma
Ursula Linne-McLaren, RN, an expert on multiple myeloma
Related Content