FDA’s ODAC to Review Data for Ide-Cel in Triple-Class Exposed R/R Myeloma

FDA

The FDA’s Oncologic Drugs Advisory Committee (ODAC) will meet to review data from the supplemental biologics license application (sBLA) seeking the approval of idecabtagene vicleucel (ide-cel; Abecma) for use in earlier lines of treatment for patients with triple-class exposed relapsed/refractory multiple myeloma.¹

Bristol Myers Squibb and 2seventy bio announced that they anticipate ODAC reviewing findings pertaining to the secondary end point of overall survival (OS) from the pivotal phase 3 KarMMa-3 trial (NCT03651128), which supported the submission of the sBLA.

Notably, the FDA informed the 2 companies that a decision on the sBLA will not be made by December 16, 2023, which was the original target action date under the Prescription Drug User Fee Act. A date for the ODAC meeting has not been confirmed.

The ODAC meeting will not affect the current indication for ide-cel, which was approved by the FDA in March 2021 for the treatment of patients with relapsed/refractory multiple myeloma after 4 or more prior lines of therapy, including an immunomodulatory drug (IMiD), a proteasome inhibitor (PI), and an anti-CD38 monoclonal antibody.²

Findings from KarMMa-3 that supported the current sBLA demonstrated that patients treated with ide-cel (n = 254) experienced a 51% reduction in the risk of disease progression or death vs those given standard-of-care (SOC) treatment (n = 132; HR, 0.49; 95% CI, 0.38-0.65; P < .001). At a median follow-up of 18.6 months (range, 0.4-35.4), ide-cel resulted in a median progression-free survival (PFS) of 13.3 months (95% CI, 11.8-16.1) vs 4.4 months (95% CI, 3.4-5.9) with SOC.³

Notably, at the time of this analysis, OS data remained immature and blinded at data cutoff.

The international, open-label, phase 3 trial enrolled patients at least 18 years of age with relapsed/refractory multiple myeloma who received 2 to 4 prior lines of therapy, including daratumumab (Darzalex), an IMiD, and a PI for at least 2 consecutive cycles and who experienced documented disease progression within 60 days after the last dose of their most recent therapy. Other key inclusion criteria consisted of measurable disease and an ECOG performance status of 0 or 1.

Patients were randomly assigned 2:1 to receive ide-cel or 1 of 5 SOC regimens. In the experimental arm, patients underwent lymphodepletion with fludarabine at 30 mg/m² and cyclophosphamide at 300 mg/m² for 3 consecutive days, followed by 2 days of no treatment before a single infusion of ide-cel at a target dose ranging from 150 × 10⁶ to 450 × 10⁶ CAR+ T cells. Notably, doses of up to 540 × 10⁶ CAR+ T cells were allowed.

The regimens for the control arm included daratumumab, pomalidomide (Pomalyst), and dexamethasone (n = 43); daratumumab, bortezomib (Velcade), and dexamethasone (n = 7); ixazomib (Ninlaro), lenalidomide (Revlimid), and dexamethasone (n = 22); carfilzomib (Kyprolis) and dexamethasone (n = 30); or elotuzumab (Empliciti), pomalidomide, and dexamethasone (n = 30).

PFS served as the trial’s primary end point. Secondary end points were comprised of overall response rate (ORR), OS, and safety.

Additional data showed patients in the ide-cel arm achieved an ORR of 71% (95% CI, 66%-77%) and complete response (CR) rate of 39%. Patients in the SOC arm experienced an ORR of 42% (95% CI, 33%-50%) and a CR rate of 5%.

Regarding safety, at least 1 any-grade adverse effect (AE) was reported in 99% of patients in the ide-cel arm vs 98% in the SOC arm. The rates of grade 3/4 AEs were 93% and 75%, respectively; grade 5 AEs occurred in 14% and 6% of patients, respectively.

The most common any-grade hematologic AEs included neutropenia (78% for ide-cel and 44% for SOC), anemia (66% and 36%), and thrombocytopenia (54% and 29%).

Any-grade infection occurred in 58% of patients treated with ide-cel vs 54% of those given SOC. The rates of grade 3/4 infection were 24% and 18% for the ide-cel and SOC arms, respectively; grade 5 infection occurred in 4% and 2% of patients, respectively.

Any-grade cytokine release syndrome (CRS) was reported in 88% of patients treated with ide-cel. The rate of grade 1/2 CRS was 83%, and 5% of patients had grade 3 or higher CRS, including 2 patients (1%) with grade 5 CRS. The median time to the first onset of CRS was 1 day (range, 1-14), and the median duration was 3.5 days (range, 1-51).

References

1. Bristol Myers Squibb and 2seventy bio provide update on US FDA review of sBLA for Abecma (idecabtagene vicleucel) in earlier lines of therapy for triple-class exposed relapsed or refractory multiple myeloma. News release. Bristol Myers Squibb and 2seventy bio. November 20, 2023. Accessed November 20, 2023. https://news.bms.com/news/details/2023/Bristol-Myers-Squibb-and-2seventy-bio-Provide-Update-on-U.S.-FDA-Review-of-sBLA-for-Abecma-idecabtagene-vicleucel-in-Earlier-Lines-of-Therapy-for-Triple-Class-Exposed-Relapsed-or-Refractory-Multiple-Myeloma/default.aspx
2. FDA approves idecabtagene vicleucel for multiple myeloma. FDA. March 26, 2021. Accessed November 20, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-idecabtagene-vicleucel-multiple-myeloma
3. Rodriguez-Ortero 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