P146 | EARLY INTRATHECAL INFUSION OF METHYLPREDNISOLONE FOR THE MANAGEMENT OF HIGH-GRADE AND STEROID-REFRACTORY ICANS IN PATIENTS WITH NON-HODGKIN LYMPHOMA TREATED WITH ANTI-CD19 CAR T-CELLS.

Immune effector cell-associated neurotoxicity syndrome (ICANS) stands as a significant and potentially life-threatening complication following chimeric antigen receptor (CAR) T-cell therapy. Current management strategies are rapidly evolving based on new research and clinical experience. We reported outcomes of patients treated with early intrathecal (IT) methylprednisolone therapy for high grade and or steroid-refractory ICANS following anti-CD19 CAR T-cell therapy. Between December 2021 and April 2024, 28 patients received CAR-T cells for relapsed/refractory non-Hodgkin lymphoma (17 DLBCL, 6 MCL, and 5 PMBCL). All patients underwent baseline neuroimaging and EEG pre-lymphodepletion and received anti-seizure prophylaxis with levetiracetam. Sixteen patients (57%) developed grade I-IV ICANS, and all of them had a previous cytokine release syndrome (CRS). One patient (6%) debuted at day +4 with grade IV ICANS unresponsive to dexamethasone, methylprednisolone, and anakinra, leading to death within 48 hours. Nine patients (56%) received early intrathecal (IT) infusion of methylprednisolone 20 mg. CAR T cells were detected in all cerebrospinal fluid (CSF) specimens tested by flow cytometry. Of these, 4 had grade III-IV ICANS and 5 had steroid-refractory grade II ICANS. Patients with grade III-IV ICANS were under dexamethasone treatment for CRS. The median day of ICANS onset was 5.5 days (range 5-6) post-infusion. These patients were treated with iv methylprednisolone, anakinra, and IT. All patients recovered from ICANS with a median of 6.5 days (range 3-12). Patients who received IT for steroid-refractory grade II ICANS had a median time of symptom onset of 7.7 days (range 6-10). Three out five were under dexamethasone for previous CRS and were treated with iv methylprednisolone + IT, and only one patient with anakinra. Two patients were initiated on dexamethasone, and due to the persistence of symptoms after 48 h, received IT. All of them recovered from symptoms in a median of 6.5 days (range 3-14). Finally, 6 patients (38%) had low-grade (I-II) ICANS with a median day of onset of 7.5 days (range 1-22) after infusion. The treatment was mainly based on dexamethasone and only 1 patient received anakinra in association. All rapidly resolved symptoms with a median time of 3.5 days (range 3-4). This single-center retrospective study suggests early IT methylprednisolone, combined with other treatments, may be an effective and safe strategy for high-grade/steroid-refractory ICANS. CAR T-cell detection in CSF supports direct central nervous system involvement in ICANS. Despite limited patient numbers, observed neurological recovery and manageable toxicity warrant further prospective studies to validate early IT therapy for improving ICANS outcomes. Early neurological monitoring and a multidisciplinary approach remain crucial.