Study Links Factors to Early Severe Hematotoxicity After CAR-T Infusion

Patients who undergo chimeric antigen receptor (CAR) T-cell therapy infusion may afterward experience immune effector cell associated hematotoxicity (ICAHT). A team of investigators has identified pre- and postinfusion factors associated with severe ICAHT in patients, as defined by the ICAHT grading system from the European Hematology Association (EHA) and European Society for Blood and Marrow Transplantation (EBMT).

Results were presented at the 2024 ASCO® Annual Meeting and the study’s lead author was Emily Liang, MD, of the University of Washington.

The study cohort involved 602 patients with hematologic malignancies who underwent CAR-T therapy at Fred Hutchinson Cancer Center and the investigators graded ICAHT that occurred up to 30 days after infusion.

Incidences of EHA/EBMT grade 1, 2, 3, and 4 ICAHT in the cohort were 53%,16%, 10%, and 6%, respectively. The investigators then used univariate and multivariable logistic regression to evaluate possible associations among these hematotoxicities with 50 patients, disease related, and laboratory factors.

The baseline patient factors linked with grade 3 to 4 ICAHT were having acute lymphoblastic leukemia (ALL), Hispanic or Latino ethnicity, and younger age. The prelymphodepletion (LD) laboratory factors included lower absolute neutrophil count, lactate dehydrogenase (LDH), C-reactive protein (CRP), and ferritin. The postinfusion factors found were peak CRP, peak ferritin, peak cytokine release syndrome (CRS) grade, and peak immune effector cell-associated neurotoxicity syndrome grade.

A multivariable model to predict grade 3 to 4 ICAHT was also constructed by the investigators. The factors it included were disease type, pre-LD absolute neutrophil count, pre-LD LDH, peak CRP, peak ferritin, and CRS grade. This model demonstrated high discrimination (C-index, 0.89) and internal validation found its sensitivity and specificity based on the Youden criteria to be 74% and 90%, respectively. It also found the CAR-HEMATOTOX score’s sensitivity and specificity in prediction of grade 3 to 4 ICAHT to be 93% and 30%, respectively.

Reference

Liang E, Albittar A, Portuguese AJ, et al. Predictors of severe hematotoxicity after CAR T-cell therapy. Abstract #7024. Presented at the 2024 ASCO® Annual Meeting; May 31-June 4, 2024; Chicago, Illinois.