FDA Approves First Cell-Based Gene Therapy for Adult Patients with Multiple Myeloma

Rare Daily Staff

The U.S. Food and Drug Administration approved Bristol Myers Squibb’s Abecma, a cell-based gene therapy to treat adult patients with multiple myeloma who have not responded to, or whose disease has returned after, at least four prior lines of therapy.

Abecma is the first cell-based gene therapy approved by the FDA for the treatment of multiple myeloma. It was originally developed by Bluebird Bio in partnership with Celgene.

“The FDA remains committed to advancing novel treatment options for areas of unmet patient need,” said Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research. “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. Today’s approval provides a new treatment option for patients who have this uncommon type of cancer.”

Multiple myeloma is rare blood cancer in which abnormal plasma cells build up in the bone marrow and form tumors in many bones of the body. This disease keeps the bone marrow from making enough healthy blood cells, which can result in low blood counts.

Myeloma can also damage the bones and the kidneys and weaken the immune system. The exact cause of multiple myeloma is unknown. According to the National Cancer Institute, myeloma accounted for approximately 32,000 new cancer cases in the United States in 2020.

Abecma is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose of Abecma is a customized treatment created by using a patient’s own T-cells, which are a type of white blood cell, to help fight the myeloma. The patient’s T-cells are collected and genetically modified to include a new gene that facilitates targeting and killing myeloma cells. Once the cells are modified, they are infused back into the patient.

The safety and efficacy of Abecma were established in a multicenter study of 127 patients with relapsed myeloma (myeloma that returns after completion of treatment) and refractory myeloma (myeloma that does not respond to treatment) who received at least three prior anti-myeloma lines of therapy. About 88 percent of patients in the study group had received four or more prior lines of anti-myeloma therapy. Overall, 72 percent of patients partially or completely responded to the treatment. Of those studied, 28 percent of patients showed complete response—or disappearance of all signs of multiple myeloma—to Abecma, and 65 percent of this group remained in complete response to the treatment for at least 12 months.

Treatment with Abecma has the potential to cause severe side effects. The label carries a boxed warning for, cytokine release syndrome (CRS), hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), neurologic toxicity, and prolonged cytopenia, all of which can be fatal or life-threatening. CRS and HLH/MAS are systemic responses to the activation and proliferation of CAR-T cells causing high fever and flu-like symptoms, and prolonged cytopenia is a drop in the number of a certain blood cell type for an extended period of time.

The most common side effects of Abecma include CRS, infections, fatigue, musculoskeletal pain, and a weakened immune system. Side effects from treatment usually appear within the first one to two weeks after treatment, but some side effects may occur later. Patients with multiple myeloma should consult with their health care professionals to determine whether Abecma is an appropriate treatment for them.

Because of the risk of CRS and neurologic toxicities, Abecma is being approved with a risk evaluation and mitigation strategy, requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Abecma.

The FDA is also requiring that hospitals and their associated clinics that dispense Abecma be specially certified, and staff involved in the prescribing, dispensing or administering of Abecma are trained to recognize and manage CRS and nervous system toxicities and other side effects of Abecma. Also, patients must be informed of the potential serious side effects and of the importance of promptly returning to the treatment site if side effects develop after receiving Abecma.

Abecma was granted Orphan Drug and Breakthrough Therapy designations by the FDA.

Photo: Peter Marks, director of the FDA’s Center for Biologics Evaluation and Research