CAR-T cell therapy, a novel type of immunotherapy and new treatment for multiple myeloma can be dangerous. It may cause potentially serious side effect similar to Parkinson’s disease.
Mount Sinai researchers are the first to report a potentially serious unexpected side effect associated with a novel type of immunotherapy called CAR-T cell therapy, which was recently licensed for the treatment of multiple myeloma.
Multiple myeloma is a complicated and incurable form of blood plasma cancer that frequently requires multiple treatments as the disease advances and develops resistance to earlier drugs, frequently resulting in chronic sickness interspersed with episodes of severe illness.
CAR-T cell treatment is a type of immunotherapy that utilizes genetically altered immune cells called chimeric antigen receptor (CAR) T cells. The CAR-T cells were utilized to target a protein called B cell maturation antigen in the particular version at issue (BCMA). BCMA is frequently detected in patients with multiple myeloma, and this therapy has demonstrated outstanding response rates in patients with highly complex, treatment-resistant multiple myeloma.
More than three months after completing a round of BCMA-targeted CAR-T cell therapy, the patient described in the Mount Sinai case study began exhibiting increasing neurological hallmarks of Parkinson’s disease symptoms, including tremors, handwriting, and gait alterations. Researchers discovered signs of BCMA protein in the brain’s basal ganglia and scarring in that location after the patient died from infection complications, suggesting that this major side effect may have been caused by the medication targeting BCMA in the brain.
“Our findings will impact the risk-benefit assessment of BCMA-targeted CAR-T cell therapy for multiple myeloma and have already led to improved monitoring and proactive management of neurologic adverse events across clinical trials of BCMA-targeted therapy,” says Dr. Oliver Van Oekelen, the first author of the study.
“This study showed that BCMA-targeted CAR-T cell therapy can cross the blood-brain barrier at least in a subset of patients to cause a progressive neurocognitive and movement disorder,” says Samir Parekh, MBBS, Professor of Medicine (Hematology and Medical Oncology), and Oncological Sciences at Icahn Mount Sinai and the corresponding author of the case study, adding “this shows that CAR-T cell therapies, although effective in multiple myeloma, warrant close monitoring for neurotoxicity, especially as such treatments acquire more widespread implementation in multiple myeloma patients.”
BCMA-targeted CAR-T treatment and comparable immunotherapies are being adopted or studied in different forms of cancer, emphasizing the significance of the findings of this study.
Clinical data, blood, spinal fluid, and brain samples were evaluated after the CAR-T infusion in this trial. CAR-T cells were discovered in the blood and spinal fluid by Mount Sinai’s Human Immune Monitoring Center, led by Miriam Merad, MD, PhD, leading scientists to conclude that this phenomenon led to CAR-T cells targeting the basal ganglia and entering the brain, causing Parkinson’s-like symptoms.
Despite the fact that this is a case study on a single patient’s reaction, a clinical trial of a BMCA-targeted CAR-T therapy found that 5% of patients in the trial had movement and neurocognitive treatment-related side effects. BCMA expression was also identified in the brains of healthy people, according to the researchers.
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