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

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. 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. Factors possibly impacting the CD4+/CD8+ ratio, such as the composition of lymphocyte population in peripheral blood at the time of apheresis, or characteristics related to the patients or to the disease, were investigated as well. Patients with a lower CAR+CD4+/CD8+ ratio in the infused products showed better outcomes in terms of responses at 3 months after CAR-T (M3) and PFS. We identified a CAR+CD4+/CD8+ ratio of 1.12 as a valuable cut-off for predicting outcomes. Moreover, patients with a lower CAR+CD4+/CD8+ ratio showed increased neurotoxicity compared to the others.image

Automated summary

CD4+ and CD8+ chimeric antigen receptor T cells (CAR-T) play different roles in the in vivo anti-tumour response, and the CD4+/CD8+ ratio may impact CAR-T efficacy.