NEW YORK (Reuters Health) – Researchers at Mount Sinai in New York have reported a previously unknown neurological side effect in a patient with multiple myeloma who received CAR-T cell therapy in a clinical trial.
The 58-year-old patient developed a progressive movement disorder with features of parkinsonism roughly three months after finishing a course of anti-B cell maturation antigen (BCMA) CAR-T therapy. His symptoms included tremors and handwriting and gait changes.
The patient later died of an infection. Postmortem analysis revealed BCMA expression on neurons and astrocytes in the patient’s basal ganglia and scarring in that area.
“This case shows the potential of BCMA-targeted CAR-T cells to cross the blood-brain barrier in a subset of patients and cause a progressive neurocognitive and movement disorder, possibly through targeting of BCMA-expressing cells of the basal ganglia,” the researchers write in a brief communication in Nature Medicine.
“Our findings suggest that anti-BCMA CAR-T cell therapies, although effective in multiple myeloma, warrant close monitoring for neurotoxicity, especially as such treatments acquire more widespread implementation,” they add.
“Our findings will impact the risk-benefit assessment of BCMA-targeted CAR-T therapy for multiple myeloma and have already led to improved monitoring and pro-active management of neurologic adverse events across clinical trials of BCMA-targeted therapy,” first author Dr. Oliver Van Oekelen said in a Mount Sinai news release.
“These patients should be monitored for neurological changes even after the acute period of cytokine release syndrome as several patients including ours developed neurocognitive changes weeks to months after CAR-T administration,” corresponding author Dr. Samir Parekh told Reuters Health by email.
“The patient had high CAR-T levels and persistence; this should also be monitored and is not currently done routinely. There is ongoing work to address this question by improving patient selection,” Dr. Parekh added.
“The benefits and risks should be evaluated for each patient and overall CAR-T remains a promising treatment. Besides monitoring, this could be addressed by improving CAR-T design to make them more specific for myeloma cells or preventing them from crossing the blood-brain barrier,” Dr. Parekh told Reuters Health.
SOURCE: https://go.nature.com/31W2auz Nature Medicine, online December 10, 2021.
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