Age and CAR T-Cell Therapy: Assessing Outcomes across Different Age Groups
Authors: Tan Jia Yi , Yeo Yong Hao , Ang Qi Xuan , Chen George , Chan Kok Hoe 
Published: December 2024

Introduction
Despite the increasing availability of chimeric antigen receptor (CAR) T-cell therapy, adults aged above 65 years old still receive this treatment at lower rates compared to their younger counterparts. The data on the impact of age on patients receiving CAR T-cell therapy is scarce. Our study aimed to investigate the impact of age on the hospital outcomes among patients who received CAR T-cell therapy.
Methods
We used Nationwide Readmissions Database (NRD), which is one of the nation's largest publicly accessible all-payer inpatient care databases, including around 18 million discharges annually. Our study included patients aged ≥18 who received CAR T-cell therapy from 2018-2020. We divided them into 3 age groups, namely young adults (18-40 years old), middle-aged adults (41-65 years old), and older adults (66 years old and above). We compared the in-hospital outcomes among these 3 different age groups. Propensity score matching (caliper of 0.2, 1:1:1 ratio) was performed using R studio. We adjusted the following confounding variables: gender, 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.
Results
Our study included 2,928 patients admitted for CAR T-cell therapy during the study period, which included 308 young adults (10.5%, average age 29.7 ± 6.9 years), 1,473 middle-aged adults (50.3%, average age 56.8 ± 6.3 years), and 1,147 older adults (39.2%, average age 71.8 ± 4.4 years). Among young adults, 56.5% were diagnosed with non-Hodgkin lymphoma (NHL), 29.9% with acute lymphocytic leukemia (ALL), 2.6% with multiple myeloma (MM), and 11.0% with unspecified malignancy. Among middle-aged adults, 72.8% were diagnosed with NLH, 15.3% with MM, 1.6% with ALL, and 10.3% with unspecified malignancy. Among older adults, 79.1 % were diagnosed with NHL, 11.9% with MM, 0.5% with ALL, and 8.5% with unspecified malignancy. From 2018 to 2020, both the proportions of young and middle-aged adults receiving CAR T-cell therapy decreased from 11.2% to 9.0% and from 54.1% to 48.4% respectively, whereas the proportion of older adults receiving CAR T therapy increased from 34.6% to 42.6%. After propensity score matching, there are 307 young adults, 307 middle-aged adults, and 299 older adults. There were no significant differences in early mortality (5.2% vs 6.2% vs 6.7%, p = 0.34), 30-day readmission (23.1% vs 23.8% 24.4%, p = 0.48), prolonged index hospitalization (96.1% vs 94.8% vs 93.6%, p = 0.14), and total length of stay (21.2 days vs 18.2 days vs 21.3 days, p = 0.58). Older patients had a higher rates of non-home discharge at 14.0% compared to young and middle-aged adults at 7.5% and 8.8% respectively. These three different age groups had comparable rates of leukopenia (45.0% vs. 42.7% vs 39.1%, p = 0.10), infection (41.0% vs 43.6% vs 42.1%, P=0.74), neurotoxicity (6.2% vs. 6.5% vs 7.7%, p = 0.52), and pulmonary embolism (1.0% vs. 2.9% vs 2.3%; p = 0.2). Older adults had a higher rates of acute kidney injury (11.7% vs 13.0% vs 18.1%, p = 0.02) and cardiac complications (2.0% vs 3.6% vs 5.4%, p = 0.03).
Conclusion
Our study found no significant differences in hospital outcomes, including early mortality, early readmission, prolonged hospitalization, and length of stay among young, middle-aged, and older adults following CAR T-cell therapy. In-hospital complications such as leukopenia, infection, neurotoxicity, and pulmonary embolism were comparable across all age groups. These findings suggest that CAR T-cell therapy is safe for older patients. However, increased vigilance for cardiac complications and acute kidney injury is crucial when managing older patients undergoing CAR T-cell therapy.