Distinct patient and product-specific phenotypes associated with toxicity and resource utilization after CAR T-cell therapy: A Nationwide Inpatient analysis.

Abstract

11193 Background: Chimeric antigen receptor (CAR) T-cell therapy improves outcomes in relapsed or refractory hematologic malignancies but is associated with significant toxicity and inpatient resource utilization. Nationally representative real-world data remain limited. We evaluated the incidence, phenotype-specific predictors, and inpatient consequences of CAR T-cell–related toxicities in U.S. practice. Methods: We conducted a retrospective cohort study using the 2023 Nationwide Inpatient Sample, identifying adult elective hospitalizations involving CAR T-cell infusion using ICD-10-PCS New Technology Group 7 codes for FDA-approved CAR-T therapies. Interhospital transfers were excluded. Cytokine release syndrome (CRS), immune effector cell–associated neurotoxicity syndrome (ICANS), and cytopenias were identified using ICD-10-CM codes during the index hospitalization; toxicity grade was unavailable. Functional status was assessed using APR-DRG loss of function severity. Primary outcomes were coded in-hospital CRS, ICANS, and cytopenias. Secondary outcomes included transfusion requirement, length of stay (LOS), and total inpatient cost, adjusted to 2023 U.S. dollars. Survey-weighted multivariable regression models evaluated predictors of toxicity and resource utilization. Results: The weighted cohort represented 3,405 CAR-T hospitalizations nationwide. Indications included multiple myeloma (42.6%), diffuse large B-cell lymphoma (32.0%), follicular lymphoma (9.0%), mantle cell lymphoma (8.6%), B-cell acute lymphoblastic leukemia (7.4%), and chronic lymphocytic leukemia (0.4%). Cytopenias were coded in 45.2% of hospitalizations, CRS in 62.6%, and ICANS in 30.1%. In adjusted analyses, cytopenias were associated with older age, B-cell acute lymphoblastic leukemia, moderate-to-severe functional impairment, and CAR-T product type. CRS risk varied by CAR-T product type and was higher among transplant recipients and patients with severe functional impairment. ICANS was associated with transplant history, selected comorbidities (including metastatic solid tumors), follicular lymphoma, older age, and CAR-T product type. Median LOS was 12 days (IQR, 9–16) and was longer among patients with neutropenia. Transfusion support was required in 6.6% of hospitalizations. Median total inpatient hospitalization cost exceeded $1.3 million and was independently associated with diffuse large B-cell lymphoma, B-cell acute lymphoblastic leukemia, neutropenia, and autologous leukapheresis. Conclusions: CAR T-cell therapy is associated with substantial inpatient toxicities, prolonged hospitalization, and high cost, with risk varying by patient and product specific phenotypes. These findings support pre-infusion risk stratification and resource-aligned inpatient care models for CAR-T delivery.