P08.11.A MANAGEMENT OF IMMUNE EFFECTOR CELL-ASSOCIATED NEUROTOXICITY SYNDROME FOLLOWING CAR-T CELL THERAPY IN CLINICAL PRACTICE: A MULTICENTRIC, RETROSPECTIVE, REAL-WORLD ANALYSIS OF TREATMENT APPROACHES AND OUTCOMES

Abstract BACKGROUND Immune effector cell-associated neurotoxicity syndrome (ICANS) is a frequent and potentially severe adverse event following chimeric antigen receptor (CAR) T-cell therapy. Although early intervention is essential, real-world data on ICANS management are still scarce. This study investigated treatment approaches and outcomes in patients with ICANS across six CAR T-certified centers in Germany. METHODS This retrospective, multicenter study evaluated treatment initiation and sequencing strategies in 165 patients with confirmed ICANS following CD19- or BCMA-directed CAR T-cell therapy. Among them, 155 (93.9%) had relapsed/refractory B-cell lymphoma, 8 (4.8%) had multiple myeloma, and 2 (1.2%) had acute lymphoblastic leukemia. The CAR T-cell products used were Axi-cel in 105 patients (63.6%), Brexu-cel in 25 (15.15%), Tisa-cel in 19 (11.5%), Liso-cel in 8 (4.8%), Ide-cel in 7 (4.2%), and Cilta-cel in 1 (0.6%). Data were collected via standardized questionnaires and medical chart reviews, focusing on the timing and therapeutic sequence of corticosteroids, IL-1 receptor antagonists, and anti-seizure therapies. RESULTS Median patient age was 64 years (19-85), and median ECOG performance status before CAR T-cell transfusion was 1 (0-3). The median duration of ICANS was 4 days (1-155), with a median ASTCT grade of 2 (1-5). Preceding or concomitant cytokine release syndrome (CRS) occurred in 163/165 patients (98.7%) with a median ASTCT grade of 2 (1-4). CNS involvement was present in 26/165 patients (15.7%). Seizure prophylaxis varied across centers: one center administered it to all 11 of its patients (11/11, 100%), two centers decided treatment in a fraction of their patients (6/17, 35.2% and 2/50, 4%), while the remaining two centers did not provide prophylaxis to any of their patients (0/87). Corticosteroids were administered in 135/165 patients (81.8%), with a median time interval of 0 days (0-4) from ICANS onset. Anakinra was used in 25/165 patients (15.2%) across five centers, with initiation at a median of 1 day (0-41) after ICANS onset. Of these, 17/25 patients (68%) received high-dose anakinra (>200mg/d). ICANS duration was significantly extended with treatment delay of anakinra (p<0.0035). Prolonged ICANS duration (>7d) was associated with inferior progression-free survival (PFS) and overall survival (p<0.068, p<0.015). In multivariate analysis, CNS involvement was an independent predictor of inferior PFS (p<0.043, HR 1.07-5.48). CONCLUSION Our study reveals discrepancies in ICANS management across treatment centers in Germany. Delayed anakinra administration was linked to prolonged ICANS duration, indicating that timely treatment may help limit the extent of neurotoxicity. Prolonged neurotoxicity was associated with inferior PFS. Future prospective studies are needed to determine the optimal timing and combination of treatment in ICANS.