FDA Approves First Cell-Based Gene Therapy for Multiple Myeloma

Rayne Rouce, M.D. - April 02, 2021

Idecabtagene vicleucel (ide-cel) is the first FDA-approved cell-based gene therapy for adults with relapsed or refractory multiple myeloma, and the first CAR T-cell therapy in the B-cell maturation antigen (BCMA) class.

On March 26, the U.S. FDA approved the use of the chimeric antigen receptor (CAR) T-cell therapy idecabtagene vicleucel (Abecma), to treat adults with multiple myeloma.

Idecabtagene vicleucel (ide-cel) is the first FDA-approved cell-based gene therapy for adults with relapsed or refractory multiple myeloma. Derived from the patient’s own T cells, this autologous cell therapy targets the tumor-associated B-cell maturation antigen (BCMA), selectively expressed on multiple myeloma and plasma cells, and importantly absent on other normal human tissues. It’s the first CAR T-cell therapy in the BCMA class.

Patients are eligible for treatment with Abecma if they have not responded to or their disease has returned after four or more lines of therapy; specifically, they must have been treated prior with a proteosome inhibitor, an anti-CD38 monoclonal antibody, and an immunomodulatory agent.

A multicenter study demonstrated the safety and efficacy of ide-cel in 127 patients with relapsed or refractory disease who had received at least three prior lines of therapy. The majority of enrolled patients (88%) had received four prior lines of therapy, informing the FDA’s decision to approve ide-cel for patients meeting this criterion. This study evaluated the efficacy of ide-cel in 100 treated patients, finding an overall response rate of 72% (95% CI: 62%, 81%). The study found a complete response rate of 28% (95% CI: 19%, 38%), the majority of whom (65%) had complete responses lasting at least 12 months. Overall and complete response rates, as well as the duration of response, were evaluated by an independent response committee using the international myeloma working group uniform response criteria for multiple myeloma.

One caveat to all CAR T-cell treatment is the risk for cytokine release syndrome (CRS) and other toxicities. Indeed, almost all patients receiving ide-cel had grade 3 or 4 toxicities, with the most common being CRS or hematological toxicities, which are manageable with current algorithms and risk mitigation training.

The impact of the FDA’s approval of ide-cel cannot be overstated. Ide-cel becomes the first approved cell-based gene therapy for refractory multiple myeloma, which remains an incurable disease despite treatment advances over the last decade. Specifically, patients with residual disease despite treatment with all three major drug classes are those with the poorest prognosis, hence the ones who stand to gain the most from this groundbreaking approval. Thus, the impact on the field of multiple myeloma will be great. Dr. Premal Lulla, a bone marrow transplant physician scientist at Baylor College of Medicine who is an active researcher in the multiple myeloma field remarks: “The impressive response rates in the refractory multiple myeloma make this therapy a very potent option for these highly refractory patients. In fact, nothing out there comes close. I look forward to the day patients can access this treatment earlier in their course, including as an option in those in whom transplant is being considered.”

The FDA granted approval of Abecma to Celgene Corporation, a Bristol Myers Squibb company.

Dr. Rouce is an assistant professor at Baylor College of Medicine and a member of the ASGCT Communications Committee.

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