The CD4/CD8 ratio of infused CD19-CAR-T is a prognostic factor for efficacy and toxicity

Abstract

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.

Keywords: CAR-T cells; CD4/CD8 ratio; apheresis; phenotype; prognostic factors.