Hypophosphatemia and thrombocytopenia: A retrospective chart review to identify markers for prediction of CRS and ICANS in CAR T-cell therapy.

Abstract

e14524 Background: CAR T-cell therapy has transformed the treatment landscape of B cell malignancies. Adverse effects of CAR T include cytokine release syndrome (CRS) and immune effector cell-associated neurotoxicity syndrome (ICANS). We aimed to identify biomarkers predictive of CRS and ICANS post CAR T-cell therapy. Methods: A total of 34 patients (19 male and 15 female) with a median age of 68 years and ranging from 38 to 80 years old treated with CAR T-cells for B-cell malignancies at Banner University Medical Center/University of Arizona Cancer Center were evaluated. Phosphate (Ph), IL-6, ferritin, lactate dehydrogenase (LDH), and platelet count from each patient were recorded through retrospective chart review. A simple two-sample t test and ANOVA T-test were run to determine statistical significances by comparing the values of each parameter of interest between groups. Results: Of the 34 patients, 19 (56%) developed CRS without ICANS, 8 (24%) had both CRS and ICANS, and 7 (20%) developed neither. Of the 19 patients with CRS without ICANS, 13 (68%) had clinical hypophosphatemia compared to 0% of patients without CRS or CRS+ICANS. Average phosphate (Ph) nadir levels in the patients with CRS were significantly lower at 2.08 mg/dL compared to those in patients without CRS at 3.20 mg/dL ( P= .00007). Patients with CRS + ICANS had even lower Ph levels at 1.99 mg/dL when compared to patients without ( P= .004). Thrombocytopenia at time of infusion was significantly associated with the development of CRS with those patients having an average platelet count of 114 x 109/L compared to 184 x 109/L in patients without CRS or CRS+ICANS (P = .037). Interleukin-6 (IL-6) levels were elevated in all of patients who developed CRS with an average peak level of 102 pg/mL, however, an inadequate number of patients without CRS or CRS+ICANS were sampled thus precluding a statistical comparison in peak IL-6 levels between groups. Conclusions: Hypophosphatemia is associated with the development of both CRS alone and CRS+ICANS after CAR T cell therapy. A proposed mechanism is thought to be related to increased phosphate consumption by CAR T cell induced metabolic activity. Thrombocytopenia at the time of infusion was significantly associated with the development of CRS. Hypophosphatemia and thrombocytopenia show promise as markers for the prediction of CRS and ICANS in CAR T-Cell therapy.