Real-world propensity score matched outcomes of CAR-T therapy in patients aged ≥65 years versus 18-64 years with DLBCL Bibek Shrestha MD , Marina Khan MD , Akshay Aluri MD , Milan Regmi MD , Ghanshyam Bhatta MD,Drew Oostra MD ,  Shahab Uddin MD , Divya Vijendra MD , Danae Hamouda MD Univeristy of Toledo Medical Center, Toledo, Ohio, USA. Southeast Health Medical Center, Dothan, Alabama, USA. Reading Hospital, West Reading, Pennsylvania 

Abstract 

Context: Chimeric antigen receptor T-cell (CAR-T) therapy has transformed the management of relapsed or refractory diffuse large B-cell lymphoma (DLBCL). However, patients aged ≥65 years remain underrepresented in pivotal clinical trials despite a high disease burden, leaving real-world comparative data limited 

Objective: This retrospective, multicenter cohort study utilized the TriNetX US Collaborative Network database from January 2018 through December 2025 to compare real-world toxicity, infectious complications, and mortality outcomes following FDA-approved CAR-T therapy between patients aged ≥65 years and those aged 18-64 years. 

Methods: Patients who underwent hematopoietic stem cell transplantation within 3 months before CAR-T infusion were excluded. To reduce baseline confounding, propensity score matching (1:1) was performed for sex, race, diabetes mellitus, hypertension, and chronic kidney disease, resulting in 388 patients in each cohort (selected from an unmatched sample of 698 patients with age group ≥65 and 423 patients with age group 18-64 adults). The primary outcome was a 30-day composite severe complication endpoint including intensive care unit admission, mechanical ventilation, sepsis, or all-cause mortality. Secondary outcomes included a 30-day cytokine release syndrome (CRS)/immune effector cell-associated neurotoxicity syndrome (ICANS) composite, alongside 90-day infectious complications and mortality. 

Results: After matching, no significant difference was observed between the patients with age group ≥65 and patients with age group 18-64 cohorts in 30-day severe complication rates (HR 0.86, 95% CI 0.56-1.31; p=0.36) or the 30-day CRS/ICANS composite (RR 0.80, 95% CI 0.56-1.14; p=0.22). At 90 days, rates remained comparable for sepsis (p=0.51), pneumonia (p=0.48), fungal infection (p=0.48), neutropenia (p=0.17), and all-cause mortality (HR 1.06, 95% CI 0.66-1.68; p=0.89). In conclusion, patients aged≥65 with DLBCL demonstrated safety and short-term survival outcomes similar to those of patients aged 18-64. 

Conclusions: In conclusion, patients in the age group ≥65 with DLBCL demonstrated similar safety and short-term survival outcomes to patients in the age group 18-64. These findings support the safety and feasibility of CAR-T therapy in fit and appropriately selected patients aged ≥65 years. Differences in patient selection and treatment approaches may contribute to observed outcomes. Further prospective studies are warranted to evaluate long-term outcomes and optimize treatment strategies across age groups