Toxicity and efficacy of chimeric antigen receptor T-cell in patients with diffuse large B cell lymphoma above the age of 70 years compare to younger patients – a matched control multi-center cohort study

Data regarding efficacy and toxicity of Chimeric antigen receptor T cells (CAR-T) therapy in older aged -geriatric population are insufficient. Since 2019, Tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory (R/R) DLBCL. From May 2019, 47 R/R DLBCL patients, ≥70 years underwent lymphopharesis in 3 Israeli centers. Elderly (n=41, mean age 76.2 years) and young (n=41, mean age 55.4 years) patients were matched based on ECOG-PS and LDH levels. There were no differences in CD4/CD8 ratio (p=.94), %CD4naiive (p=.92), %CD8 naive (p=.44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T products in both cohorts. Forty-one elderly patients (87%) received CAR-T infusion. There were no differences in the incidence of grade ≥3 cytokine-release-syndrome (p=.29), grade≥3 neurotoxicity (p=.54), and duration of hospitalization (p=.55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (p=.145). Response rates were similar between the 2 groups (CR-46% and PR-17% in the elderly group, p=.337). Non-relapse-mortality at 1 and 3 months was 0 in both groups. With a median follow up of 7 (range, 1.3-17.2) months, 6- and 12-months progression-free and overall survival in elderly were 39% and 32%, and 74% and 69%, respectively. EORTC QLQ-C30 questionnaires, obtained at 1 month, showed worsening of disability and cancer-related-symptoms in elderly vs younger patients. We conclude that outcomes of CAR-T cell therapy are comparable between older aged-geriatric and younger patients, indicating that age as per se should not preclude CAR-T administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.