70 岁以上与较年轻弥漫大 B 细胞淋巴瘤患者接受 CAR-T 细胞治疗的毒性与疗效——一项匹配对照多中心队列研究

Data regarding efficacy and toxicity of chimeric antigen receptor T (CAR-T) cell therapy in the elderly, geriatric population are insufficient. In 2019, tisagenlecleucel and axicabtagene-ciloleucel were commercially approved for relapsed/refractory diffuse large B-cell lymphoma. From May 2019 onwards, 47 relapsed/refractory diffuse large Bcell lymphoma patients, 70 years underwent lymphopharesis in three 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 performance status and lactose dehydrogenase levels. There were no differences in CD4/CD8 ratio (P=0. 94), %CD4 naive (P=0. 92), %CD8 naive (P=0. 44) and exhaustion markers (both HLA-DR and PD-1) between CAR-T cell products in both cohorts. Forty-one elderly patients (87%) received CAR-T cell infusion.

There were no differences in the incidence of grade 3 cytokine-release-syndrome (P=0. 29), grade 3 neurotoxicity (P=0. 54), and duration of hospitalization (P=0. 55) between elderly and younger patients. There was no difference in median D7-CAR-T cell expansion (P=0. 145). Response rates were similar between the two groups (complete response 46% and partial response 17% in the elderly group, P=0.

337). Non-relapse mortality at 1 and 3 months was 0 in both groups. With a median follow-up of 7 months (range, 1. 3-17. 2 months), 6- and 12-months progression-free and overall survival in elderly patients 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 versus younger patients.

We conclude that outcomes of CAR-T cell therapy are comparable between elderly, geriatric and younger patients, indicating that age as per se should not preclude CAR-T cell administration. Longer rehabilitation therapy is essential to improve disabilities and long-term symptoms.