By Blood Cancers Today Staff Writers - Last Updated: March 18, 2024
In considering the supplemental Biologics License Application (sBLA) for idecabtagene vicleucel (ide-cel; ABECMA®), the US Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) voted that the benefits of treatment outweigh the risks for patients with relapsed or refractory multiple myeloma (MM).
The 11-member panel of independent experts voted eight in favor and three against. Prior to the vote, the ODAC panel discussed the supporting overall survival data and risk-benefit analysis from the KarMMa-3 trial.
The original FDA approval for ide-cel granted an indication for adult patients with relapsed or refractory MM after four or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. The sBLA proposes an updated indication that would allow ide-cel to be used in earlier lines of therapy.
The ODAC Chair, Ravi Madan, MD, of the Center for Cancer Research of the National Cancer Institute, voted no, commenting that, “this data at this level of maturity really didn’t provide convincing evidence that ide-cel earlier had a favorable risk-benefit assessment. In the proposed indication as the question asked there are relatively higher grade 3 and 4 toxicities with this treatment. It seems like the bridging therapy strategies really need to be optimized further. And while the [progression-free survival (PFS)] is quite remarkable, the ultimate readouts of similar overall survival, again, question whether earlier is truly better in this setting. I think that at this level of analysis, this data (for me) left a little bit more [to be desired] to provide clarity to answer in the affirmative for this question.”
Voting in favor of ide-cel, Christopher Lieu, MD, of University of Colorado, said, “I struggled with this decision given what I feel are data that are concerning for two reasons. The prolonged trend toward overall survival detriment in those 15 months, as well as a lack of durable PFS tail, suggest a response that’s not quite as durable as one might hope given what we’re asking our patients to go through. Patients have to be aware of the risk associated with the treatment in the early months, whether it’s related to ide-cel or just the risk burden that patients are going to carry with them during the bridging period, which is still part of this overall treatment paradigm. Having said that, the prolonged PFS difference is significant and offers our patients a chance of significant time-off therapy with associated quality of life improvements … I do believe that the risk-benefit profile is favorable for this population as a whole, but it’s a closer margin than I think we would like. Patients will need to have in-depth discussions … with their provider.”
Sagar Lonial, MD, of Winship Cancer Institue of Emory University School of Medicine, who provided background on the disease during the ODAC meeting, said, “moving [chimeric antigen receptor (CAR)] T-cell access to earlier in the treatment course allows patients to be treated with a broader range of more effective bridging therapies, particularly in the context of ‘refractoriness’—and we’ve seen this in the context of real-world data where the frequency of patients going from collection to infusion is a much greater percentage than in most clinical trials.”
Ide-cel was also given a positive recommendation for its Marketing Authorization application in Europe by the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency.
While recommendations from the FDA ODAC are nonbinding, the FDA typically follows positive recommendations from the advisory committee when making regulatory decisions.
Original Source: ODAC Panel Votes in Favor of Supplemental FDA Application for Ide-Cel | Blood Cancers Today