Comparative Real-World Outcomes of CAR-T Therapy in Elderly (‚â•70‚ÄâYears) Versus Younger ( <‚Äâ70‚ÄâYears) Patients with Diffuse Large B-Cell Lymphoma
Introduction/Background/Significance: Chimeric antigen receptor T-cell (CAR-T) therapy has revolutionized management for relapsed/refractory diffuse large B-cell lymphoma (DLBCL), but real-world safety and efficacy data remain sparse in the elderly population, who are underrepresented in pivotal trials. Understanding the age-related differences in mortality, toxicities, and complications is essential for optimizing patient selection and supportive care.
Materials and Methods/Case Presentation/Objective: A retrospective, multicenter cohort analysis was conducted using the TriNetX Global Collaborative Network, evaluating patients with DLBCL treated with CAR-T therapies. Patients were divided into two cohorts: aged ≥70 years (n=716) and aged 18–69 years (n=716), matched 1:1 for demographics, comorbidities, prior stem cell transplant, and prior therapies including lenalidomide, cyclophosphamide, rituximab, doxorubicin, cytarabine, cisplatin, and gemcitabine. Outcomes were assessed over a 1-year period post–CAR-T therapy initiation using Kaplan-Meier analysis. Hazard ratios (HR) and log-rank p-values were calculated for each outcome.
Results/Description/Main Outcome Measures: All-cause mortality at 1 year was similar between elderly and younger patients (HR 1.08, 95% CI 0.87–1.33, log-rank p=0.50). Hospitalization (HR 1.00, 0.68–1.46, p=0.98), emergency room visits (HR 1.08, 0.76–1.55, p=0.66), and outpatient visits (no events in either group) showed no significant differences by age. Biomarker elevations, including IL-6 ≥40 pg/mL (HR 0.93, 0.56–1.55, p=0.78), CRP ≥10 mg/L (HR 0.98, 0.78–1.22, p=0.84), IL-10 ≥18 pg/mL (HR 0.51, 0.05–5.59, p=0.57), and LDH >250 U/L (HR 1.19, 0.81–1.74, p=0.38) were not significantly different between groups.
Hematologic and neurologic toxicities were frequent but similar by age: neutropenia (HR 0.82, 0.65–1.04, p=0.11), thrombocytopenia (HR 1.07, 0.82–1.39, p=0.63), anemia (HR 1.14, 0.81–1.60, p=0.47), and neurotoxicity (HR 1.28, 0.94–1.76, p=0.12). Infectious complications, including septic shock (HR 1.46, 0.80–2.67, p=0.21), pneumonia (HR 1.13, 0.80–1.62, p=0.49), CMV infection (HR 0.80, 0.47–1.37, p=0.41), candidemia (HR 0.99, 0.14–7.04, p=0.99), and aspergillosis (HR 0.75, 0.17–3.35, p=0.70), were also not significantly different by age.
Rates of cytokine release syndrome (CRS) (HR 0.81, 95% CI 0.64–1.02; log-rank p=0.075) and immune effector cell–associated neurotoxicity syndrome (ICANS) (HR 0.97, 0.69–1.36; log-rank p=0.863) were similar between elderly and younger cohorts.
The only statistically significant difference was seen in rates of hypogammaglobulinemia, which were higher in the elderly cohort (HR 1.36, 1.09–1.70, p=0.007), though rates of IVIG requirement did not differ significantly (HR 1.20, 0.97–1.49, p=0.09). There were no age-related differences in rates of secondary myeloid neoplasms (MDS: HR 1.23, 0.51–2.97, p=0.65; AML: HR 0.57, 0.24–1.36, p=0.20), fatigue (HR 1.21, 0.90–1.63, p=0.20), or ESRD/hemodialysis (HR 1.00, 0.32–3.09, p=1.00).
Conclusions: In this large, real-world, propensity-matched analysis, elderly DLBCL patients (‚â•70‚Äâyears) who received CAR-T therapy experienced similar rates of 1-year mortality, hospitalizations, hematologic and infectious complications, including ICAN and CRS, compared to younger adults. The main age-associated difference was a higher rate of hypogammaglobulinemia in older patients, underscoring the importance of immunoglobulin monitoring and supportive care in this population. These findings suggest that advanced age alone should not preclude CAR-T therapy, though vigilant monitoring for immune complications is warranted in elderly DLBCL patients.
