FDA Approves First Cell-Based Gene Therapy for Multiple Myeloma

FDA recently approved Abecma, the first cell-based gene therapy to treat adult patients with multiple myeloma who have not responded to or whose disease has returned after previous therapy. 

Bristol Myers Squibb and bluebird bio’s 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 using a patient’s own T-cells. 

The patient’s T-cells are collected and genetically modified to include a new gene that targets and kills myeloma cells. Once the cells are modified, they are infused back into the patient, FDA explained. 

“CAR T cell therapies have shown transformational potential for the treatment of hematologic malignancies, and we, along with our partners at bluebird, are proud to bring the first CAR T cell therapy to appropriate triple-class exposed patients with relapsed or refractory multiple myeloma,” Samit Hirawat, MD, chief medical officer at Bristol Myers Squibb, said in a press release following the authorization. 

FDA based its approval on a multicenter study of 127 patients with relapsed myeloma. In the study, 88 percent of patients had received four or more prior lines of antimyeloma therapy and 72 percent of patients partially or completely responded to the treatment.

Of all patients, 28 percent showed a complete response or disappearance of all signs of multiple myeloma with Abecma, while 65 percent of this group remained in complete response to the treatment for nearly a year after the study ended. 

Researchers found that the most common side effects of Abecma were cytokine release syndrome, infections, fatigue, musculoskeletal pain, and a weakened immune system.

But FDA warned that treatment with Abecma has the potential to cause severe side effects, including hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), neurologic toxicity, and prolonged cytopenia. 

CRS and HLH/MAS are systematic responses to the activation of CAR-T cells causing high fever and flu-like symptoms. Prolonged cytopenia is a drop in the number of certain blood cell type for an extended period of time. 

All of these side effects are life-threatening and can be fatal. 

Because of these risks, FDA approved Abecma with a risk evaluation and mitigation strategy.

Specifically, FDA is requiring that hospitals that dispense Abecma be specially certified. And staff involved in the prescribing, dispensing, or administering of Abecma must be trained to recognize and manage CRS, nervous system toxicities, and other side effects. 

The agency is also requiring the manufacturer to conduct a post-marketing observational study involving patients treated with Abecma. Patients must be informed of the potential serious side effects and of the importance of returning to the treatment side if side effects develop after receiving the drug. 

Despite the side effects, the FDA-approved gene therapy is a step in the right direction for cancer patients, according to Nikhil C. Munshi, MD, associate director of The Jerome Lipper Multiple Myeloma Center at Dana-Farber Cancer Institute.

“Patients with relapsed or refractory multiple myeloma are in critical need of new therapies,” said Munshi, MD, in the release. 

“With the approval of ide-celas the first anti-BCMA CAR T cell therapy, we are excited to finally be able to offer patients a new, effective personalized treatment option that is delivered through a single infusion,” Munshi continued. 

According to the National Cancer Institute, multiple myeloma accounted for nearly 1.8 percent, or 32,000, of all new cancer cases in the US in 2020.

Top pharmaceutical companies, including Sanofi and Pfizer, have reported positive results from studies of their independent antibody myeloma treatments. 

Last June, Sanofi announced that Sarclisa, added to carfilzomib and dexamethasone, reduced the risk of relapsed multiple myeloma progression or death in patients by 47 percent compared to placebo.

And in December, Pfizer stated that 83 percent of patients in its ongoing Phase 1 study of its investigational multiple myeloma antibody drug achieved clinical response at the highest dose level.