Leflunomide eyed for steroid-sparing ICANS care

Researchers outline a mitochondrial-targeting strategy that could offer a new path toward steroid-sparing management of CAR T-cell neurotoxicity.

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Leflunomide is identified as a prototype candidate for managing immune effector cell-associated neurotoxicity syndrome (ICANS) following CAR T-cell therapy.
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The proposed mechanism involves mitochondrial dysfunction amplifying neuroinflammation, which is not adequately addressed by current steroid-based treatments.
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Leflunomide's active metabolite, teriflunomide, inhibits DHODH, affecting mitochondrial reactive oxygen species and inflammatory pathways.
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The authors suggest a staged evaluation pathway for leflunomide, starting with preclinical studies and leading to randomized clinical trials.
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Current management of ICANS primarily relies on corticosteroids, which may not be effective for all patients and can lead to adverse effects.

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