输注的 CD19-CAR-T 的 CD4/CD8 比值是疗效与毒性的预后因素

CD4 + and CD8 + chimeric antigen receptor T cells (CAR-T) play different roles in the in vivo anti-tumour response, but the role of the CD4 + /CD8 + ratio among infused CAR-T has not been clearly defined yet.

We analysed leftovers from infused anti-CD19 CAR-T bags of 31 patients with aggressive B-cell lymphomas. The median ratio was 1. 44, lower for brexu-cel compared to tisa-cel and axi-cel. The CAR+CD4 + /CD8 + ratio was influenced by lactate dehydrogenase levels at apheresis, not by age, previous treatments or the CD4 + /CD8 + ratio in peripheral blood. Patients with a response at 3 months after CAR-T (M3) had a lower CAR+CD4 + /CD8 + ratio in the infused products compared to non-responders (ratio 0.

74 vs. 2. 47, p = 0. 011). A CAR+CD4 + /CD8 + ratio higher than the cut point of 1. 12 was associated with an increased risk of treatment failure at M3 (OR 23. 3, p = 0. 012) and M6 (OR 10, p = 0. 028). The median 6-month PFS was 76% for patients with a ratio lower than 1. 12% vs. 31% for the others. The prognostic role of the CAR+CD4 + /CD8 + ratio was independent of the costimulatory domain (CD28 vs. 4-1BB) of the product (OR 16. 41, p = 0. 041).

Our data indicate a crucial role for CD8 + CAR-T and the CAR+CD4 + /CD8 + ratio in predicting CAR-T efficacy.