FDA Approves Ide-Cel in Previously Treated Multiple Myeloma

Findings from the phase 3 KarMMa-3 trial (NCT03651128) supported the FDA approval of idecabtagene vicleucel for patients with relapsed or refractory multiple myeloma.

Idecabtagene vicleucel (Abecma; ide-cel) is now approved by the FDA for the treatment of relapsed/refractory multiple myeloma after at least 2 prior lines of therapy that included an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, according to a press release from developers Bristol Myers Squibb and 2seventy bio, Inc.¹

The approval is based on results from the phase 3 KarMMa-3 trial (NCT03651128), in which ide-cel was compared with standard-of-care (SOC) therapy. At the primary progression-free survival (PFS) analysis with a median follow-up of 15.9 months, the median PFS was 13.3 months (95% CI, 11.8-16.1) in the ide-cel arm vs 4.4 months (95% CI, 3.4-5.9) in the SOC arm (HR, 0.49; 95% CI, 0.38-0.64; P <.0001). Additionally, the 6-month PFS rate was 73% vs 40%, and at 12 months it was 55% vs 30%.²

The press release highlighted the new recommended dose of ide-cel is 300 to 510 x 10⁶ CAR-positive T cells. Toxicity in the boxed warning included cytokine release syndrome, neurologic toxicities, hemophagocytic lymphohistiocytosis/macrophage activation syndrome, prolonged cytopenia, and secondary hematological malignancies.

“[Ide-cel] has demonstrated a [PFS] benefit 3 times that of standard regimens in relapsed or refractory multiple myeloma, and we are now bringing the promise of cell therapy to patients earlier in their treatment journey,” Bryan Campbell, senior vice president, head of Commercial, Cell Therapy, Bristol Myers Squibb, said in the press release.¹ “This approval underpins our commitment to addressing the unmet needs of more patients living with multiple myeloma by improving upon the current treatment paradigm, and we remain steadfast in our pursuit of innovation and advancing cell therapy research to deliver potentially transformative therapies.”

In March 2024, the FDA Oncologic Drugs Advisory Committee (ODAC) held a meeting to discuss if ide-cel showed a favorable risk/benefit ratio to this patient population.³ The committee voted 8 to 3 in favor of ide-cel.

“I think the progression-free survival 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, Saul A. Rosenberg, MD, professor of Lymphoma at Stanford Medicine during the ODAC meeting.³

Additionally, in March 2024, the European Commission approved ide-cel in the aforementioned patient population.⁴

References

1. U.S. FDA approves Bristol Myers Squibb and 2seventy bio’s Abecma for triple-class exposed relapsed or refractory multiple myeloma after two prior lines of therapy. News release. Bristol Myers Squibb. April 5, 2024. Accessed April 5, 2024. https://shorturl.at/abglC
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. March 15, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live March 15, 2024. Accessed April 5, 2024. https://shorturl.at/fmxz7
4. 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 April 5, 2024. https://tinyurl.com/4cmdxxkt