On 26 March 2021, the US Food and Drug Administration (FDA) approved idecabtagene vicleucel (Abecma, Bristol Myers Squibb) for the treatment of adult patients with relapsed or refractory multiple myeloma after four or more prior lines of therapy, including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody. This is the first FDA-approved cell-based gene therapy for multiple myeloma.
Idecabtagene vicleucel is a B-cell maturation antigen (BCMA)-directed genetically modified autologous chimeric antigen receptor (CAR) T-cell therapy. Each dose is customised using a patient’s own T-cells, which are collected and genetically modified, and infused back into the patient.
Safety and efficacy were evaluated in a multicentre study of 127 patients with relapsed and refractory multiple myeloma who received at least three prior lines of antimyeloma therapies; 88% had received four or more prior lines of therapies. Efficacy was evaluated in 100 patients who received idecabtagene vicleucel in the dose range of 300 to 460×106 CAR-positive T-cells. Efficacy was established based on overall response rate (ORR), complete response (CR) rate, and duration of response (DoR), as evaluated by an Independent Response committee using the International Myeloma Working Group Uniform Response Criteria for Multiple Myeloma.
The ORR was 72% (95% confidence interval [CI] 62%, 81%) and CR rate was 28% (95% CI 19%, 38%). An estimated 65% of patients who achieved CR remained in CR for at least 12 months.
The idecabtagene vicleucel label carries a boxed warning for cytokine release syndrome (CRS), neurologic toxicities, haemophagocytic lymphohistiocytosis/ macrophage activation syndrome, and prolonged cytopaenias. The most common side effects of idecabtagene vicleucel include CRS, infections, fatigue, musculoskeletal pain, and hypogammaglobulinemia.
Idecabtagene vicleucel is approved with a risk evaluation and mitigation strategy requiring that healthcare facilities that dispense the therapy must be specially certified to recognise and manage CRS and nervous system toxicities. To evaluate long-term safety, the FDA is requiring the manufacturer to conduct a post-marketing observational study involving patients treated with idecabtagene vicleucel.
The recommended dose range for idecabtagene vicleucel is 300 to 460×106 CAR-positive T-cells.
Full prescribing information for Abecma is available here.
This application was granted breakthrough therapy designation and orphan drug designation.
Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System.
For assistance with single-patient INDs for investigational oncology products, healthcare professionals may contact FDA’s Oncology Center of Excellence Project Facilitate.
