Ide-Cel Receives Favorable ODAC Vote for R/R Multiple Myeloma

The ODAC meeting concluded that ide-cel showed a favorable risk/benefit profile for patients with pretreated relapsed/refractory multiple myeloma.

An 8 to 3 vote was cast by the FDA Oncologic Drugs Advisory Committee (ODAC) on the use of intravenous infusion of idecabtagene vicleucel (ide-cel; Abecma) in patients with pretreated relapsed/refractory multiple myeloma.¹

The FDA previously accepted a supplemental biologics license application (sBLA) for ide-cel in relapsed/refractory multiple myeloma in April 2023.² ODAC focused on survival data from the phase 3 KarMMa-3 trial (NCT03651128), which supported the sBLA for ide-cel in this indicaiton.3 Results from the trial found significant survival benefit in the ide-cel arm vs standard care.

“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.

“I voted no. This was a challenging one. Our goal is to help patients experience life better. The benefit is clearly that PFS is improved, but what are the risks? The risks are PFS and the data we have now appears transient and there is no clear benefit that early [treatment] is better than later,” explained Daniel Spratt, MD, professor in the department of Radiation Oncology in the School of Medicine and a member of Developmental Therapeutics Program and Case Comprehensive Cancer Center.

A total of 254 patients were enrolled in the ide-cel group vs 132 in the standard care group. Lymphodepletion occurred with fludarabine given at 30 mg/m2 and cyclophosphamide at 300 mg/m2 for 3 consecutive days followed by 2 days of no treatment and then 1 infusion of ide-cel at 150×106 to 450×106 CAR-positive T cells.

Leukapheresis occurred in 249 patients in the ide-cel group, and 1 patient received bridging therapy without leukapheresis, so the ide-cel group included 250 patients overall. The median ide-cel dose given to 225 patients was 445×106 CAR-positive T cells.

For the interim analysis, the median follow-up was 18.6 months. The median progression-free survival (PFS) was 13.3 months (95% CI, 11.8-16.1) with ide-cel vs 4.4 months (95% CI, 3.4-5.9) in the standard care arm (HR, 0.49; 95% CI, 0.38-0.65; P <.001). At 6 months, the PFS rate was 73% vs 40%, and at 12 months it was 55% vs 30% in the ide-cel and standard care arms, respectively.

A partial response or better occurred in 71% (95% CI, 66%-77%) of patients in the ide-cel group vs 42% (95% CI, 33%-50%) in the standard care arm. Stringent complete responses occurred in 39% of patients in the ide-cel group vs 5% in the standard care group.

The median time to response was 2.9 months vs 2.1 months, and the median duration of response was 14.8 months (95% CI, 12.0-18.6) vs 9.7 months (95% CI, 5.4-16.3) in the ide-cel and standard care groups, respectively. The minimal residual disease negativity status at 3 months was confirmed in 20% of patients in the ide-cel group and 1% in the standard care group.

Grade 3/4 adverse effects (AEs) occurred in 93% of patients in the ide-cel group vs 75% in the standard care group, with grade 5 AEs occurring in 14% vs 6%. The most common AEs in each respective arm included neutropenia (78% vs 44%), anemia (66% vs 36%), and thrombocytopenia (54% vs 29%).

A total of 58% of patients in the ide-cel group developed an infection vs 54% in the standard regimen group. Grade 3/4 events occurred in 24% vs 18%, and grade 5 events affected 4% vs 2%.

Cytokine release syndrome was noted in 88% of patients in the ide-cel arm, with 2 patients having grade 5 events. The median time to onset was 1 day, and the median duration was 3.5 days.

A total of 109 patients died, with the most common cause being disease progression between both arms (17% vs 17%). Death due to infectious disease occurred in 5% vs 5%, respectively.

References

1. March 15, 2024 Meeting of the Oncologic Drugs Advisory Committee (ODAC). Streamed live March 15, 2024. Accessed March 15, 2024. https://shorturl.at/fmxz7
2. 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 April 17, 2023. bit.ly/3ULmLZt
3. 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