Early neurologic response predicts outcomes after anakinra for immune effector cell–associated neurotoxicity syndrome

ABSTRACT: Anakinra is increasingly used for corticosteroid-refractory and/or severe immune effector cell-associated neurotoxicity syndrome (ICANS) following chimeric antigen receptor (CAR) T-cell therapy; however, robust data on its efficacy and predictors of response are lacking. We evaluated the outcomes of 101 patients treated with anakinra for ICANS (corticosteroid-refractory, n = 90) and investigated factors associated with anakinra efficacy. The median time to ICANS resolution from anakinra initiation was 8 days, and the 28-day cumulative incidences of ICANS resolution and treatment-related mortality (TRM) were 86% and 13%, respectively. Anakinra treatment failure occurred in 28%. The day +28 antitumor response rate was 91% (complete response, 47%). Significant neurologic improvement (SNI; ≥2-grade improvement in ICANS) occurred in 43% of patients within 72 hours after anakinra initiation. Achieving 72-hour SNI was associated with faster time to ICANS resolution (median, 3 vs 9 days; P< .001) and hospital discharge (28-day cumulative incidence, 93% vs 53%; P< .001), lower 2-week cumulative exposure to dexamethasone (120 vs 190 mg; P = .029) and anakinra (3650 vs 6600 mg; P = .059), lower TRM (28-day cumulative incidence, 0% vs 21%; P = .011), and a trend toward superior overall survival (28 days, 98% vs 74%; P = .094). In multivariable analysis, older age, CAR T-cell product type, and higher day 0 C-reactive protein were independently associated with lower odds of 72-hour SNI. Our study benchmarks key clinical outcomes after anakinra treatment for ICANS; 72-hour SNI may provide a practical clinical decision point to identify patients who may require additional treatment strategies.