Scientists from Mount Sinai recently discovered potentially serious side effects associated with a new form of immunotherapy known as CAR-T cell therapy, which was recently approved for the treatment of multiple myeloma. The research has been published in the “Nature Medicine Journal”.
Multiple myeloma is a complex, incurable type of blood plasma cancer that often required multiple treatments as the disease progressed and became resistant to previous treatments, often resulting in chronic disease with periods of acute illness. CAR-T cell therapy used genetically engineered immune system cells known as chimeric antigen receptor (CAR) T cells. In the specific version at issue, CAR-T cells were used to target a protein known as B cell maturation antigen (BCMA). BCMA is commonly found in multiple myeloma, and this therapy has shown impressive response rates in people with particularly complex and treatment-resistant multiple myeloma.
More than three months after completing a course of BCMA-targeted CAR-T cell therapy, the patient described in the Mount Sinai case study began to show progressive neurological features of Parkinson-like symptoms, including tremors as well as changes in handwriting and gait. The patient later died of infection, and researchers found evidence of BCMA protein in the basal ganglia of the brain and scarring in this area, suggesting that this serious side effect could be due to the targeting therapy. BCMA in the brain. “Our results will impact the assessment of the risks and benefits of BCMA-targeted CAR-T cell therapy for multiple myeloma and have already led to better monitoring and proactive management of adverse neurological events in the context of multiple myeloma. BCMA-targeted therapy clinical trials, ”said Oliver Van Oekelen, MD, doctoral student at Icahn School of Medicine at Mount Sinai and first author of the manuscript.
Samir Parekh, MBBS, Professor of Medicine (Hematology and Medical Oncology) and Oncology Sciences at Icahn Mount Sinai and corresponding author of the case study, added: “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 progressive neurocognitive and movement disorder. This shows that CAR-T cell therapies, although effective in multiple myeloma, warrant close monitoring of neurotoxicity, especially as these treatments acquire a more widespread implementation in patients with multiple myeloma. “CAR-T therapy targeted by BCMA and similar immunotherapies are used or tested in other types of cancer, this which underlines the importance of the results of this study.
In this study, researchers analyzed clinical data, blood, cerebrospinal fluid, and brain samples after the CAR-T infusion. The Mount Sinai Human Immunity Monitoring Center, led by Miriam Merad, MD, PhD, found CAR-T cells in blood and cerebrospinal fluid, which has led scientists to believe that this phenomenon led CAR-T cells to target the basal ganglia and infiltrate the brain to cause Parkinson’s-like symptoms. While these results are limited by the inherent fact that this is a single patient response case study, a clinical trial of BMCA-targeted CAR-T therapy also reported that five for One hundred of the patients in the trial underwent neurocognitive and movement therapy. -related side effects. Researchers also found evidence of BCMA expression in the brains of healthy individuals.
The study was the result of a multidisciplinary effort between myeloma physicians, neurologists, radiologists, pathologists and immunologists from Mount Sinai and was funded by National Cancer Institute grants R01 CA244899 and CA252222. (ANI)
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