FDA/EMA Accept Ide-Cel Applications for Earlier R/R Multiple Myeloma Use

Data from the phase 3 KarMMA-3 trial support several applications for idecabtagene vicleucel in earlier use for triple-class exposed multiple myeloma in the United States, Europe, and Japan.

The FDA has accepted a supplemental biologics license applications for idecabtagene vicleucel (ide-cel; Abecma) for earlier treatment of adult patients with relapsed or refractory multiple myeloma who have previously been exposed to an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody, according to a press release from Bristol Myers Squibb.1

In the phase 3 KarMMa-3 trial, ide-cel produced a median PFS of 13.3 months vs 4.4 months with placebo in patients with relapsed or refractory multiple myeloma.

In the phase 3 KarMMa-3 trial, ide-cel produced a median PFS of 13.3 months vs 4.4 months with placebo in patients with relapsed or refractory multiple myeloma.

The FDA has set a Prescription Drug User Fee Act date of December 16, 2023 for ide-cel in this indication.

The European Medicines Agency has also accepted a type 2 variation application for ide-cel in relapsed or refractory multiple myeloma. Additionally, the Ministry of Health, Labour and Welfare in Japan has accepted a supplemental new drug application for the agent in the same indication.

Supporting data for the regulatory applications came from the phase 3 KarMMa-3 trial (NCT03651128), in which investigators evaluated ide-cel compared with 1 of 5 standard regimens in patients with relapsed or refractory multiple myeloma. With a median follow-up of 18.6 months, findings published in The New England Journal of Medicine highlighted a median progression-free survival (PFS) of 13.3 months with ide-cel vs 4.4 months with standard regimens (HR, 0.49; 95% CI, 0.38-0.65; P <.001).2 Additionally, the overall response rate (ORR) was 71% and 42% in each respective treatment group (P <.001).

Safety results in the KarMMa-3 trial were consistent with previously reported data.

“The KarMMa-3 study has shown the clear clinical benefit of [ide-cel] over existing standard-of-care regimens and, if approved, the potential for this anti-BCMA CAR T-cell therapy to become a standard of care earlier in the treatment course for relapsed and refractory multiple myeloma,” Adam Lenkowsky, senior vice president and head of Major Markets at Bristol Myers Squibb, said in the press release. “These global regulatory acceptances of [the] applications represent important additional progress across 3 regions with significant patient need in triple-class exposed multiple myeloma.”

In the international, open-label, phase 3 KarMMa-3 trial, investigators randomly assigned patients 2:1 to either receive ide-cel at a dose range of 150 x 106 to 450 x 106 CAR T cells) or a standard regimen, which included daratumumab (Darzalex) plus pomalidomide (Pomalyst) and low-dose dexamethasone; daratumumab plus bortezomib (Velcade) and dexamethasone; ixazomib (Ninlaro) plus lenalidomide (Revlimid) and dexamethasone; carfilzomib (Kyprolis) plus dexamethasone; and elotuzumab (Empliciti) plus pomalidomide and dexamethasone.

The primary end point was PFS. Secondary end points included overall survival, event-free survival, ORR, minimal residual disease, duration of response, adverse effects, and pharmacokinetics.

Patients 18 years and older who had a documented diagnosis of multiple myeloma and measurable disease and received at least 2 but no greater than 4 prior lines of therapy were eligible for enrollment on the KarMMa-3 trial. Additional inclusion criteria included having an ECOG performance status of 0 or 1, adequate vascular access for leukapheresis, and recovery from any non-hematologic toxicities to grade 1 or baseline.

Patients who had any significant medical condition preventing them from participating in the study or non-secretory multiple myeloma were not able to enroll on the trial. Patients were also unsuitable for enrollment if they had a history of prior malignancies other than multiple myeloma, active or prior plasma cell leukemia, known central nervous system involvement, or received autologous stem cell transplantation within 12 weeks prior to randomization.


  1. 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
  2. Rodriguez-Otero P, Ailawadhi S, Arnulf B, et al. Ide-cel or standard regimens in relapsed or refractory multiple myeloma. N Engl J Med. 2023;388:1002-1014. doi:10.1056/NEJMoa2213614
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