Demographic Characteristics, Incidence and Outcomes of Cytokine Release Syndrome and Immune Effector Cell-Associated Neurotoxicity Syndrome in Patients Undergoing CAR T-Cell Therapy: An Analysis of the National Inpatient Sample (NIS) - 2021

Background: Chimeric Antigen Receptor (CAR) T-cell therapy is a groundbreaking treatment for several cancers such as multiple myeloma, certain types of lymphoma and leukaemia but can lead to severe adverse events, including Cytokine Release Syndrome (CRS) and Immune Effector Cell-Associated Neurotoxicity Syndrome (ICANS). We aim to investigates the incidence and outcomes of CRS and ICANS among patients undergoing CAR T-cell therapy.

Methods: We utilized the 2021 National Inpatient Sample (NIS) database, identifying patients who underwent CAR T-cell therapy using the International Classification of Diseases (ICD)-10 diagnosis and procedure codes, Z92.850, XW033C3, and XW043G7. CRS was identified using the code D89.83, and ICANS was identified with the code G92. Descriptive statistics and survey-weighted logistic regression analyses were conducted to examine the prevalence and outcomes of CAR T-cell therapy patients. Linear regression models adjusted for potential confounders were also employed to analyze the prevalence of CRSS and ICANS, as well as their associations with Length of Stay (LOS) and Total Hospitalization charges (TOTCHG).

Results: Out of 6,666,752 hospitalizations during the study period, 400 patients received CAR T-cell therapy. Among CAR T-cell therapy recipients, 60% were male, with a mean age of 53.1 years. Racial distribution showed 67.95% White, 5.13% Black, and 16.67% Hispanic patients. The Charlson Comorbidity Index indicated a high comorbidity burden (score ≥ 3) in 50% of patients. Regarding hospital region, 35% of the total patients were treated in the Northeast, 25% in the Midwest, 20% in the South, and 20% in the West.

CRS and ICANS were observed in 195 (48.75%) and 25 patients (6.25%), respectively. The overall mortality rate for patients undergoing CAR T-cell therapy was 2.5%. For those with both CRS and CAR T-cell therapy, the mortality rate was significantly higher at 5.0%, but ICANS and CART-cell therapy showed 0 deaths. Logistic regression revealed that hospitals with higher patient volumes were significantly associated with lower odds of CRS mortality (medium (Odds Ratio (OR) = 0.017, p = 0.015) and large (OR = 0.064, p = 0.042) hospital bed sizes). All the other factors did not show any statistical significance.

The mean hospital LOS among CAR T-cell therapy recipients was 12.83 days (95% CI: 10.44-15.21, p < 0.001), with regression analysis showing that treatment in teaching hospitals significantly increased LOS (Coefficient: 11.66, p = 0.005). Adjusted regression analysis indicated that the presence of CRS and ICANS did not show statistical significance in terms of LOS. The mean total hospitalization charges among CAR T-cell therapy recipients were $823,072 (95% CI: $483,404-$1,162,741, p < 0.001). Adjusted regression analysis identified race (specifically Black and Asian/Pacific Islander patients) and the Charlson comorbidity index as significant predictors of increased hospital charges (p = 0.001, p = 0.024, and p = 0.033 respectively). CAR- T cell therapy patients with associated CRS further increased hospital charges by $615,661 (95% CI: $161,139–$1,070,182; p = 0.008).

Conclusion: CAR T-cell therapy is associated with substantial complications and costs, particularly due to high rates of CRS. Mortality was significantly higher in patients with CRS. Hospitals with higher patient volumes demonstrated better outcomes in terms of CRS mortality, indicating the importance of experience in managing these patients. Longer hospital stays were notable, especially in teaching hospitals, and increased total hospitalisation charges were notable among patients based on race, comorbidity, and incidence of CRS. Further research is needed to elucidate the factors that might be impacting the treatment and outcomes among patients receiving CAR T-cell therapy.