Researchers propose leflunomide to prevent CAR T brain toxicity
Researchers at the University of California, Irvine published a perspective arguing that damaged mitochondria can create a self-sustaining inflammatory feedback loop that helps drive immune effector cell-associated neurotoxicity syndrome (ICANS) after CAR T-cell therapy. They applied a four-part checklist to evaluate candidate drugs and found that leflunomide satisfies cellular relevance, brain penetration, an acceptable safety profile, and supporting evidence from other inflammatory brain conditions; its active metabolite teriflunomide is measurable in cerebrospinal fluid. The authors propose staged laboratory studies and randomized trials to test leflunomide as a steroid-sparing option, but the idea remains untested in patients.
Leflunomide is proposed as a candidate to prevent ICANS.
Context
CAR T-cell therapy can cause a brain complication called ICANS. The paper proposes a mitochondrial mechanism and suggests testing leflunomide next. Researchers call for lab work and clinical trials to follow.
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