First-in-human study of FLT3 CAR-T cell therapy for relapsed acute myeloid leukemia

Abstract In this first-in-human open-label study, autologous FLT3 CAR-T cells were delivered to two patients with relapsed and refractory FLT3 + AML. Bone marrow examination revealed AML blasts with high but variable surface density of FLT3 expression. Following tumor cytoreduction and lymphodepletion, 1 × 10 6 /kg of FLT3 CAR-T cells were administered, resulting in in vivo CAR-T cell expansion and grade 1 cytokine release syndrome in both patients. Both patients failed to achieve remission after CAR-T cell therapy, but bone marrow examination following therapy revealed the elimination of FLT3 + AML blasts, persistence of FLT3 − AML blasts, and early post-treatment preservation of normal CD34 + hematopoietic stem and progenitor cells (HSPCs) with variable FLT3 expression. Collectively, autologous FLT3 CAR-T cells can be safely administered and can eradicate FLT3⁺ blasts with minimal toxicity, without causing substantial damage to normal CD34⁺ HSPCs; however, they fail to induce leukemic remission due to the heterogeneity of FLT3 expression and the persistence of FLT3⁻ AML blasts.