Intrathecal Chemotherapy as a Potential Treatment for Steroid-refractory Immune Effector Cell-associated Neurotoxicity Syndrome.

BACKGROUND/AIM:Chimeric antigen receptor (CAR) T-cell therapy has revolutionized the treatment of various B-cell malignancies. However, it can cause serious adverse effects like immune effector cell-associated neurotoxicity syndrome (ICANS). ICANS is attributed to disruption of the blood-brain barrier due to inflammatory cytokines and increased levels of immune effector cells (IECs) in the cerebrospinal fluid (CSF). Corticosteroids and supportive management are the mainstays of ICANS treatment. However, no guidelines exist for the treatment of steroid-refractory ICANS. Some reports have shown favorable outcomes with no long-term complications in patients with steroid-refractory ICANS treated with intrathecal (IT) chemotherapy. CASE REPORT:We describe the outcomes of two patients with steroid-refractory ICANS treated with IT chemotherapy. Both patients had refractory large B-cell lymphoma and were not candidates for autologous transplant. They developed steroid-refractory ICANS after CAR T-cell infusion. IT chemotherapy with 12 mg methotrexate and 50 mg hydrocortisone resulted in prompt neurological improvement in both patients. One of them passed away due to multiple other comorbidities, and the other patient continues to do well without any complications. CONCLUSION:IT chemotherapy could be considered as a potential approach for the management of steroid-refractory ICANS based on our experience. Prospective studies are needed to validate this approach.