Members of the Oncologic Drugs Advisory Committee (ODAC), an external advisory group to the U.S. Food and Drug Administration (FDA), voted 8-3 and 11-0 in favor of idecabtagene vicleucel (ide-cel) and ciltacabtagene autoleucel (cilta-cel), respectively, as second-line treatments for relapsed or refractory (R/R) multiple myeloma (MM).
Standard treatments for MM include immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies. For those patients with R/R MM who are triple-class exposed (TCE) early in treatment, there remains no effective standard of care. Ide-cel and exa-cel, highly effective B-cell maturation antigen-directed T-cell immunotherapy therapies, offer a treatment option for patients who are TCE in which their own T-cells are genetically modified ex vivo before infusion.
The committee’s endorsement of ide-cel and cilta-cel comes after the submission of indication extensions by Celgene Corporation and Janssen Biotech Inc., respectively. Both drugs were previously approved by the FDA (ide-cel in March 2021; cilta-cel in February 2022) as treatments for adult patients with R/R MM following the results of the respective KarMMa-3 and CARTITUDE-4 trials, in which researchers demonstrated significant delays in disease progression compared with standard therapies. Now, ODAC has endorsed earlier administration of both drugs as treatment for these patients, with ide-cel proposed for those who have received an immunomodulatory agent, proteasome inhibitor, and anti-CD38 monoclonal antibody, and cilta-cel for those who have received at least one prior line of therapy (including a proteasome inhibitor), an immunomodulatory agent, and are refractory to lenalidomide.
Though ODAC ultimately endorsed the two therapies, concerns about treatment-associated risks persist, especially regarding data from both studies that illustrate an increased rate of early death among the ide-cel and cilta-cel arms compared with standard therapy regimens.
“There [are] numerically greater early deaths,” said Daniel Spratt, MD, of Case Western Reserve University, who voted against ide-cel, adding, “I believe there’s still uncertain potential of worse overall survival.”
Other committee members who voted in favor of either drug said the risk profile made it more difficult to come to a decision. Christopher Lieu, MD, of the University of Colorado, said of ide-cel, “The risk-benefit profile is favorable for this population as a whole, but it’s a closer margin than we’d like.” He voted to approve the drug because “the PFS [progression-free survival] is prolonged, significant, and offers our patients a chance of significant time off therapy with associated quality-of-life improvement.”
“The treating oncologist will have to have a serious conversation with the patient when it comes time to choose this option to explore the increased risk of death,” said Mary Kwok, MD, of Fred Hutchinson Cancer Center, in explaining her approval of cilta-cel. “I look forward to future data to help us understand … what we can do to improve.”
Source: FDA, March 15, 2024.
