The first cell-based gene therapy for multiple myeloma has been approved by the US Food and Drug Administration. Approval of the Idecabtagene vicleucel pertains to those patients who progressed on or could not respond to minimum four before lines of the therapy, including a kind of immunomodulator, a PI, and an anti CD38 antibody.
A form of chimeric antigen receptor (CAR) T-cell therapy, Idecabtagene vicleucel is the first agent in the group to target B cell maturation antigen (BCMA).
According to Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, “The cure for multiple myeloma is minimal, the long-term outlook can vary based on the person’s age as well as the stage of the condition during the time of diagnosis.”
“The approval offers a new treatment option for those patients who have this uncommon sort of cancer,” Peter Marks added.
B cell maturation antigen is expressed by almost all the cells of myeloma. Ide-cel basically binds to B cell maturation antigen expressing cells, responsible for the cells of death.
Major supporting findings for the approval noted from the phase-II KarMMa carried out a trial involving a total of 127-patients with r/r myeloma, 100 of whom could be assessed for the response.
The findings demonstrated an ORR of 72% and stringent complete responses (sCR) in 28% of the patients. The median time to response was noted as 30-days, and, median duration of the response was noted as 11-months, increasing to 19-months for those patients who have touched the sCR.
Decreased-grade cytokine release syndrome (CRS) noted in 85 percent of patients, and the grade ≥3 cytokine release syndrome noed in 9 percent of patients. Neurotoxicity reported in 28 percent of patients, reaching grade ≥3 severity in 4-percent of patients.
Hemophagocytic lymphohistiocytosis or macrophage activation syndrome (HLH/MAS) noted in 4 percent of patients, 1 of whom died of multiorgan Hemophagocytic lymphohistiocytosis or macrophage activation syndrome with cytokine release syndrome. A 2’nd patient died of bronchopulmonary aspergillosis with Hemophagocytic lymphohistiocytosis or macrophage activation syndrome as the contributing factor.
According to principal investigator Nikhil C. Munshi, MD, of Dana-Farber Cancer Institute, “On behalf of KarMMa carried out study, ide-cel elicited quick responses in the almost maximum of patients, and these deep as well as durable responses were noted in patients with the triple class exposed and refractory MM.”
“As a treating healthcare professional, I often work together with patients with RRMM who are in the critical requirement of the new therapies.
With this approval of the first anti BCMA CAR T cell therapy, we are curious to finally be able in order to provide patients a new, impactful personalized treatment option which is primarily delivered with the help of a single infusion,” Munshi stated.
Due to the risk of cytokine release syndrome, neurotoxicity, and hemophagocytic lymphohistiocytosis or macrophage activation syndrome, approval of the ide-cel includes a few of boxed warnings regarding adverse reactions and needs a risk evaluation as well as mitigation strategy.