Sex Difference in Outcomes of CAR T-Cell Therapy
Authors: Tan Jia Yi , Yeo Yong Hao , Wong Kha Kin Hermon , Ang Qi Xuan , Chisti Mohammad Muhsin , Ezekwudo Daniel 
Published: December 2024

Introduction
Chimeric Antigen Receptor (CAR) T-cell therapy has emerged as a revolutionary treatment for hematologic malignancies. However, the impact of sex difference on the outcomes of CAR T-cell therapy is not well-established. Our study aimed to investigate how sex difference affect hospital outcomes following CAR T-cell therapy.
Methods
Using the Nationwide Readmissions Database (NRD), our study included patients aged ≥18 who received CAR T-cell therapy from 2018-2020 and divided them into male and female groups. We compared the hospital outcomes and in-hospital complications among these two groups. Propensity score matching (caliper of 0.2, 1:1 ratio) was performed. We adjusted the following confounding variables: age, comorbidities such as cardiovascular diseases including hypertension, coronary artery disease, congestive heart disease, and valvular heart disease, diabetes mellitus, hyperlipidemia, cerebrovascular accident, obstructive sleep apnea, liver disease, pulmonary disease, chronic kidney disease, obesity, anemia, and social factors including smoking, alcohol use, and illicit drug use. Further analyses were conducted using propensity score-matched study populations. We first performed univariable matched analysis. Patients' variables were then included in a multivariable model for conditional logistic regression analyses. Analysis was performed using R studio software.
Results
Our study included 2,928 patients admitted for CAR T-cell therapy during the study period, which included 1,832 male (62.6%, average age 60.3 ± 13.7 years) and 1,096 female (37.4%, average age 59.1 ± 13.8 years). Among male patients, 75.1% were diagnosed with non-Hodgkin lymphoma (NHL), 12.2% with multiple myeloma (MM), 3.6% with acute lymphocytic leukemia (ALL), and 9.1% with unspecified malignancy. Among female patients, 70.9% were diagnosed with NHL, 13.2% with MM, 5.1% with ALL, and 10.8% with unspecified malignancy. After propensity score matching, there were 1,092 male and 1,092 female. Throughout the study period, the postprocedural early mortality rates increased in both sexes (males, 1.9% in 2018 Q1-Q2 to 5.7% 2020 Q3-Q4 [P=0.47]; females, 5.4% in 2018 Q1-Q2 to 6.9% 2020 Q3-Q4 [P=1.00]); the postprocedural 30-day readmission rates decreased in both sexes (males, 23.1% in 2018 Q1-Q2 to 17.6% 2020 Q3-Q4 [P=0.06]; females, 20.8% in 2018 Q1-Q2 to 19.3% 2020 Q3-Q4 [P=0.45]). Through multivariate analysis, females were not associated with worse hospital outcomes after CAR T-cell therapy compared to males (early mortality, adjusted odd ratios [aOR]: 1.04 [95% CI 0.69-1.57]; 30-day readmission, aOR: 1.05 [95% CI 0.86-1.30]; non-home discharge, aOR: 0.89 [95% CI 0.60-1.31]; prolonged index hospitalization more than 7 days, aOR: 0.89 [95% CI 0.60-1.31]). In terms of in-hospital complications, female patients were associated with higher odds of leukopenia (aOR: 1.26 [95% CI 1.06-1.50]), but lower odds of acute kidney injury (aOR: 0.68 [95% CI 0.52-0.88]) than their male counterparts. Female patients did not have higher odds of other in-hospital complications, including neurotoxicity (aOR: 1.06 [95% CI 0.76-1.49]), infection (aOR: 1.05 [95% CI 0.88-1.26]), pulmonary embolism (aOR: 0.40 [95% CI 0.09-1.75]), and cardiac complications (aOR: 1.40 [95% CI 0.83-2.36]) compared to the male patients.
Conclusion
There was no sex difference in hospital outcomes, including early mortality, 30-day readmission, non-home discharge, and prolonged index hospitalization after CAR T-cell therapy. However, our study shows that females had higher odds of leukopenia but lower odds of acute kidney injury compared to males. There were no significant differences in other in-hospital complications such as neurotoxicity, infection, pulmonary embolism, and cardiac complications between male and female patients.