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.
By
Andrea Surnit
August 20, 2026
Clinical Scorecard: Leflunomide eyed for steroid-sparing ICANS care
At a Glance
Category Detail
Condition Immune effector cell-associated neurotoxicity syndrome (ICANS) Key Mechanisms Mitochondrial dysfunction and neuroinflammation feedforward loop Target Population Patients undergoing CAR T-cell therapy Care Setting Clinical evaluation of mitochondrial-targeting drugs
Key Highlights
Leflunomide identified as a prototype candidate for ICANS management Mitochondrial dysfunction may amplify neuroinflammation Current treatments include corticosteroids, which may lead to steroid-refractory disease Leflunomide's mechanism involves DHODH inhibition affecting mitochondrial function Proposed evaluation pathway includes preclinical studies and randomized clinical trials Guideline-Based Recommendations
Diagnosis
ICANS is characterized by systemic cytokine elevation followed by CNS inflammatory amplification Management
Corticosteroids are the mainstay treatment but may not be effective for all patients Monitoring & Follow-up
Careful timing of leflunomide initiation relative to CAR T-cell infusion is recommended Risks
Potential impairment of CAR T-cell expansion due to DHODH inhibition Patient & Prescribing Data
Patients with ICANS post-CAR T-cell therapy
Leflunomide's active metabolite, teriflunomide, shows CNS exposure and has been used in other inflammatory conditions
Clinical Best Practices
Consider uridine supplementation to rescue DHODH inhibition effects Evaluate mitochondrial-targeting drugs in a staged approach from preclinical to clinical trials Related Resources & Content
