The Food and Drug Administration (FDA) has granted approval to idecabtagene vicleucel (ide-cel, Abecma), a CAR T-cell therapy, for the treatment of adult patients with relapsed or refractory multiple myeloma who have received at least four prior lines of therapy, including a proteasome inhibitor, an immunomodulatory agent, and an anti-CD38 monoclonal antibody. This approval marks a significant advancement in the treatment landscape for patients with limited options.
Efficacy in Heavily Pretreated Patients
The approval was primarily based on the results of a clinical trial where a single infusion of ide-cel demonstrated a 72% overall response rate in heavily pretreated multiple myeloma patients. Specifically, 44% of patients experienced a partial reduction in tumor size, while 28% achieved a complete remission. The median duration of remission for all responders was 11 months, and for those achieving complete remission, it was 19 months. These results are particularly noteworthy given that additional therapies for this patient population typically provide only 3 to 4 months of benefit and rarely eliminate the cancer entirely.
Targeting BCMA with CAR T-Cell Technology
Ide-cel is a CAR T-cell therapy that targets B-cell maturation antigen (BCMA), a protein highly expressed on multiple myeloma cells but present in only a small subset of healthy white blood cells. The therapy involves collecting a patient's T cells, genetically engineering them to express a CAR that recognizes BCMA, and then infusing the modified T cells back into the patient. This process enhances the immune system's ability to specifically target and destroy multiple myeloma cells.
James Kochenderfer, M.D., a senior investigator at NCI's Center for Cancer Research, noted, "This work builds on earlier work conducted by my group at NCI that showed CAR T cells could be an effective treatment for multiple myeloma." He also cautioned that further research is needed to improve the treatment and achieve permanent cures.
Safety Considerations and Side Effects
While ide-cel offers a promising treatment option, it is associated with potentially serious side effects. In the clinical trial, nearly all participants (99%) experienced some adverse reaction. Common side effects included fatigue, infections, and cytokine release syndrome (CRS). The FDA approval includes a boxed warning for CRS, hemophagocytic lymphohistiocytosis/macrophage activation syndrome (HLH/MAS), neurotoxicity, and prolonged cytopenia.
Cytokine release syndrome occurred in 85% of patients, with 9% experiencing severe reactions, and HLH/MAS was observed in 4% of patients. Neurological side effects, such as confusion, seizure, and speech impairment, occurred in 28% of patients. Due to these risks, the FDA mandates that healthcare providers prescribing and administering ide-cel be trained to recognize and manage these side effects, and that patients be monitored for at least 4 weeks post-infusion.
Origins and Development
The BCMA-targeted CAR T-cell therapy was initially developed by Dr. Kochenderfer and his colleagues at the NCI in 2013. The technology was subsequently licensed by bluebird bio and further developed under a cooperative research agreement between NCI, bluebird bio, and Bristol Myers Squibb. The first clinical study of ide-cel was led by Dr. Kochenderfer at NCI, with the first five patients being treated at the institute. One patient with advanced multiple myeloma who had not responded to standard therapies experienced a 39-month remission after treatment with ide-cel.
Impact on Patient Care
The approval of ide-cel provides a valuable new treatment option for patients with relapsed or refractory multiple myeloma who have exhausted other available therapies. While the treatment carries significant risks, the potential for durable remissions and improved quality of life makes it an important advancement in the field. As Dr. Kochenderfer stated, "Patients are usually very happy after they get the CAR T-cell therapy because, for the first time in a long time, they have a lot of energy."
