Hypophosphatemia as a Marker for Immune Effector Cell-Associated Neurotoxicity Syndrome in Chimeric Antigen Receptor T Cell Recipients

Background: Hypophosphatemia is a common electrolyte abnormality in patients receiving chimeric antigen receptor T-cell (CAR-T) therapy. Its relationship with immune effector cell-associated neurotoxicity syndrome (ICANS) remains incompletely understood. This study investigates the incidence, timing, and clinical correlates of hypophosphatemia and its relationship with ICANS. Methods: This is a retrospective chart review of patients who received CAR-T therapy at an academic center. Hypophosphatemia was defined as <2.5 mg/dL post-CAR-T infusion. Timing of ICANS and phosphate trends were collected. Cases where hypophosphatemia occured before ICANS were cosindered as exposed. Ordinal logistic regression, linear regression, and time-dependent Cox model evaluated the relationship between ICANS and phosphate trends. Results: Of 186 CAR-T recipients, 75 had non-Hodgkin’s lymphoma (NHL), 103 multiple myeloma (MM), and 8 leukemia. ICANS occurred in 37.1% of patients (95% CI: 30.1%–44.5%). Hypophosphatemia occurred in 71.5% (95% CI: 64.4%-77.8%). Mean nadir phosphate was 1.78 mg/dL (95% CI: 1.7–1.84), occurring at median of 5.94 days post-infusion (95% CI: 5.12–6.7). After adjusting for age and other confounding variables, hypophosphatemia was associated with increased ICANS risk (HR 2.87, P = 0.0001) (Figure 1) and preceded ICANS by a median of 2 days (95% CI: 0.83-3.2, P < 0.001 Wilcoxon). In NHL patients, lower nadir phosphate predicted earlier and higher ICANS grade (β = –1.76, P < 0.001). Conclusion: ICANS is frequently seen after the onset of hypophosphatemia post-CAR-T. It's preceeded and possibly predicted by hypophosphatemia which raises the question: Can hypophosphatemia be used as an early predictive tool for ICANS?Figure 1 Based on time-dependant cox model. Hypophosphatemia was linked to shorter ICANS-free time (HR 2.87, 95% CI 1.63–5.1, P=0.001)