FDA approves Abecma, first CAR T-cell therapy for multiple myeloma
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The FDA approved idecabtagene vicleucel, a chimeric antigen receptor T-cell therapy, for treatment of adults with relapsed or refractory multiple myeloma.
The indication applies to patients who received at least four previous lines of therapy, including an immunomodulatory agent, a proteasome inhibitor and an anti-CD38 monoclonal antibody.
Idecabtagene vicleucel (Abecma; Bristol Myers Squibb, bluebird bio), also known as ide-cel, is a genetically modified autologous CAR T-cell therapy that targets the B-cell maturation antigen (BCMA) when it is expressed on the surface of cancer cells.
The agent is the first CAR T-cell therapy to be approved by the FDA for commercial use in patients with multiple myeloma. It also is the first time the FDA has approved a CAR T-cell therapy that targets BCMA; all previously approved CAR T cells have targeted CD19, a protein commonly found on the surface of B-cell malignancies.
The FDA based approval of ide-cel on results of the ongoing pivotal KarMMa trial, a multicenter phase 2 study that to date has enrolled 127 patients with relapsed or refractory multiple myeloma who received at least three previous lines of antimyeloma therapy.
The most recent efficacy results showed 72% (95% CI, 62-81) of patients responded to ide-cel, with 28% (95% CI, 19-38) achieving a stringent complete response, according to a press release from the agent’s manufacturer. Sixty-five percent of patients with a stringent complete response to therapy remained in remission for at least 12 months.
The significance of ide-cel’s approval — including its role as the first cellular therapy approved by the FDA for multiple myeloma — cannot be overstated, according to Nikhil C. Munshi, MD, director of basic and correlative science within Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute and professor of medicine at Harvard Medical School.
“It’s very important because of the incredible effectiveness of this treatment, even in this late disease stage,” Munshi, one of the primary investigators for the KarMMa trial, told Healio. “Its ability to provide total responses and ones that are sustained is so incredible, and none of the current treatments in the field are able to achieve this level of activity.”
There should be tremendous demand for ide-cel among patients who qualify, Munshi said.
“I think there will be great excitement and a rush to start providing patients with this therapy,” he said.
Safety results of the KarMMa trial showed 85% of patients treated with ide-cel experienced some form of cytokine release syndrome (CRS), with 9% having grade 3 or greater CRS. One patient in the study died of complications related to CRS.
Neurotoxicity was reported among 28% of patients who received ide-cel, with 4% experiencing grade 3 or greater neurotoxicity-related adverse events.
Five patients in the KarMMa trial (4%) experienced hemophagocytic lymphohistiocytosis (HLH)/macrophage activation syndrome (MAS), a potential adverse effect of CAR T-cell therapy that is related to excessive immune activation. One patient with HLH/MAS and CRS died of bronchopulmonary aspergillosis, with HLH/MAS determined to be a contributing factor to the death. The other three cases of HLH/MAS in the study were resolved, according to the manufacturer.
Ide-cel will include a boxed warning that outlines risks for CRS, neurotoxicity, HLH/MAS and prolonged cytopenia associated with CAR T-cell therapy. The FDA also has required the manufacturer to conduct a post-marketing observational study of patients treated with ide-cel to comply with its Risk Evaluation and Mitigation Strategy monitoring program.
“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” Peter Marks, MD, PhD, director of the FDA’s Center for Biologics Evaluation and Research, said in an agency-issued press release.
“While there is no cure for multiple myeloma, the long-term outlook can vary based on the individual’s age and the stage of the condition at the time of diagnosis,” Marks added. “[This] approval provides a new treatment option for patients who have this uncommon type of cancer.”
For more information:
Nikhil C. Munshi, MD, can be reached at nikhil_munshi@dfci.harvard.edu.
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