The decision to vote in favor of idecabtagene vicleucel comes after positive phase 3 trial results demonstrating its efficacy compared with standard regimens.
The FDA has announced that the Oncologic Drugs Advisory Committee (ODAC) voted in favor of idecabtagene vicleucel (ide-cel, Abecma; Bristol Myers Squibb) for patients with triple-class exposed relapsed or refractory multiple myeloma. This decision was based off positive and pivotal results from the phase 3 KarMMa-3 study (NCT03651128) which were presented at the American Society of Hematology (ASH) Annual Meeting and Exposition in December 2023.1
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Ide-cel is a chimeric antigen receptor (CAR) T cell therapy that is able to recognize and bind to the B-cell maturation antigen (BCMA) on the surface of multiple myeloma cells. This leads to CAR T-cell proliferation, cytokine secretion, and the cytolytic killing of BCMA-expressing cells. Ide-cel is the first FDA-approved BCMA-directed CAR T-cell immunotherapy for the treatment of adult patients with relapsed or refractory multiple myeloma who have had 4 or more prior lines of therapy (including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The ODAC noted their recommendation will be considered by the FDA for its ongoing review of the supplemental biologics license application (sBLA) for ide-cel in this patient population.1
“We are extremely pleased with the positive outcome of the ODAC meeting, which recognizes the favorable benefit/risk profile of [ide-cel], and based on results from the KarMMa-3 study, we are confident in the significant clinical benefit that [ide-cel] delivers for patients with triple-class exposed relapsed or refractory multiple myeloma, an incurable disease with no clear effective standard of care in earlier lines of therapy,” said Anne Kerber, senior vice president, head of Late Clinical Development, Hematology, Oncology and Cell Therapy, Bristol Myers Squibb, in a press release. “We look forward to working with the FDA as it completes review of our sBLA in order to bring this potentially transformative therapy to more patients in need.”1
KarMMa-3 is a pivotal, open-label, global, randomized, controlled phase 3 trial that evaluated ide-cel to standard regimens for the treatment of adult patients with relapsed or refractory multiple myeloma who had received 2 to 4 prior lines of treatment and were refractory to the last received treatment regimen. The enrolled patients were randomly assigned to receive either ide-cel or standard regimens of treatment that consisted of combinations that included daratumumab, pomalidomide, and dexamethasone (DPd); daratumumab, bortezomib, and dexamethasone (DVd); ixazomib, lenalidomide, and dexamethasone (IRd); carfilzomib and dexamethasone (Kd); or elotuzumab, pomalidomide, and dexamethasone (EPd), which was chosen for patients based on their most recent treatment regimen.2
The primary end point for the study is progression-free survival (PFS) and secondary end points included overall response rate (ORR) and overall survival (OS). The trial followed results from KarMMa-2 (NCT03601078), a phase 2 study which also assessed the efficacy and safety of ide-cel.2
The study results indicated that at a median follow-up period of 30.9 months (range: 12.7-47.8 months), PFS was significantly approved and maintained after treatment with ide-cel compared with standard regimens (13.8 months vs 4.4 months), with a 51% reduction in the risk of disease progression or death. The investigators note that the follow-up median of 30.9 is the longest for a randomized phase 3 trial that assesses CAR T cell therapy in this patient population.2
The authors also note that ide-cel had also demonstrated higher ORRs, with those treated with ide-cel having an ORR of 71% (95% CI: 66-77) and a complete response (CR) rate of 44% (95% CI: 38-50). In addition, standard regimens demonstrated and ORR of 41% (95% CI: 34-51) and a CR rate of 5% (95% CI: 2-9).2
Trial Name: Efficacy and Safety Study of bb2121 Versus Standard Regimens in Subjects With Relapsed and Refractory Multiple Myeloma (RRMM) (KarMMa-3)
ClinicalTrials.gov ID: NCT03651128
Sponsor: Celgene
Completion Date (Estimated): April 8, 2027
“The favorable and supportive outcome of the ODAC meeting brings us another step closer to expanding the benefits of Abecma to myeloma patients earlier in their treatment course,” said Anna Truppel-Hartmann, senior vice president, Clinical Research and Development, 2seventy bio. “We believe in the strength of the KarMMa-3 data and remain committed to increasing treatment options and improving outcomes for patients living with multiple myeloma.”1
Further, the investigators note that because of the median PFS that was observed with standard regimens, over half of patients (56%) who had received standard regimens had crossed over to receive ide-cel as a following therapy. The median OS for ide-cel was 41.4 months (95% CI: 30.9-NR) and 37.9 months (95% CI: 23.4-NR; 95% CI: 0.73-1.40; HR: 1.01) for the standard treatment regimens; however, the sensitivity analyses which were adjusted for the cross over showed a median OS of 41.4 months for ide-cel (95% CI: 30.9-NR) and 23.4 months for standard regimens (95% CI: 17.9-NR), indicated a positive trend in OS for ide-cel.2
“With patients becoming triple-class exposed earlier in the multiple myeloma treatment paradigm, it is critical that new treatment options with the potential to improve long-term outcomes are available as early as possible,” said Sagar Lonial, MD, FACP, professor and chair, Department of Hematology & Medical Oncology, Emory University School of Medicine, chief medical officer, Winship Cancer Institute of Emory University, in the press release.1
In the study, there were no new safety signals for ide-cel, with primarily low-grade occurrences of cytokine release syndrome (CRS) and neurotoxicity reported by patients. Approximately 88% of patients treated with ide-cel had experienced any grade CRS, and 4% of patients reported experiencing grade 3 or 4 CRS events. Further, 2 patients (1%) reported experiencing a grade 5 event. For neurotoxicity, 15% of patients experienced any grade and 3% reported having grade 3 or 4 occurrences.2
“We are thankful that today’s ODAC vote recognizes this unmet need and helps to advance ide-cel, a novel treatment option with demonstrated clinically meaningful benefit, for patients with triple-class exposed relapsed or refractory multiple myeloma,” said Lonial.1
