Age-related differences in clinical outcomes among hospitalized recipients of CAR-T cell therapy: A national readmission database analysis

Abstract Background: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized the treatment of relapsed/refractory hematologic malignancies. However, age-related differences in response, toxicity, and survival outcomes remain underexplored. Given the increasing use of CAR-T in older populations, understanding how age affects inpatient outcomes is essential for improving treatment planning and supportive care strategies. Methods: We conducted a retrospective cohort study using the 2021–2022 National Readmission Database (NRD) to examine the impact of age on clinical outcomes among adult patients (≥18 years) hospitalized for CAR-T therapy for multiple myeloma, non-Hodgkin lymphoma, or acute leukemia. Patients were stratified into two age groups: ≥65 years and <65 years. Outcomes of interest included in-hospital mortality, length of stay (LOS), and treatment-related complications. Rao-Scott chi-square tests and design-adjusted Kruskal-Wallis tests were used to compare groups. Results: A total of 3,519 weighted hospitalizations were identified: 1,519 (43%) in patients aged ≥65 years and 2,000 (57%) in those <65 years. Patient population was predominantly male in both groups (65% vs 62%). Older patients had a greater comorbidity burden, including higher rates of chronic kidney disease (15% vs. 5.6%, p<0.001), atrial fibrillation/flutter (18% vs. 5.6%, p<0.001), coronary artery disease (12% vs. 2.5%, p<0.001), hypertension (55% vs. 32%, p<0.001), hyperlipidemia (34% vs. 20%, p<0.001), and anemia (18% vs. 14%, p=0.025). The median LOS was similar between the groups (14 days [IQR 10–20] for ≥65 vs. 14 [10–19] for <65; p=0.6). In-hospital mortality was numerically higher in the older cohort (4.8%) compared to younger patients (3.0%), though this difference was not statistically significant (p=0.14). Treatment-related complications differed between age groups. Patients ≥65 years had significantly higher rates of encephalopathy (21% vs. 11%, p<0.001) and cytokine release syndrome (CRS) (67% vs. 58%, p<0.001). Acute kidney injury (AKI) occurred more frequently in older patients (18% vs. 13%, p=0.053). RBC transfusion needs were higher in younger patients (12% vs. 9.1%, p=0.064), though not statistically significant. Other complications, including CMV infection, GI bleeding, tumor lysis syndrome, hemophagocytic lymphohistiocytosis, and platelet transfusion, did not differ significantly between age groups.Conclusion: Among hospitalized CAR-T recipients, there was no statistically significant difference in in-hospital mortality or length of stay between older (≥65 years) and younger patients. However, older adults experienced higher rates of encephalopathy and cytokine release syndrome, highlighting the need for closer monitoring and tailored supportive care. These findings suggest that while CAR-T therapy is feasible across age groups, older patients may benefit from proactive toxicity management strategies.