Anti-CD7 CAR-T cells in patients with relapsed or refractory CD7+ Acute Myeloid Leukemia: First-in-human phase I study

Abstract Background The prognosis for patients with relapsed/refractory acute myeloid leukemia (R/R AML) remains poor, highlighting an urgent need for effective therapies. Chimeric antigen receptor T-cell (CAR-T) therapy has advanced efficacy for hematological malignancies. However, current CAR-T therapies mostly target myeloid-lineage antigens, such as CD123, CLL1, and CD33, which may be associated with potential hematopoietic toxicity. CD7 is expressed in approximately 30% of AML cases, and preclinical studies showed its anti-CD7 CAR-T efficacy in AML xenograft models. We report here on the use of anti-CD7 CAR-T cells in the treatment of R/R AML patients. Methods This single-arm phase I clinical trial evaluated anti-CD7 CAR-T cells in patients with CD7+ R/R AML. Patients with R/R AML underwent leukapheresis and lymphodepletion chemotherapy with cyclophosphamide and fludarabine or etoposide before CAR-T cell infusion. Dose escalation was based on the 3+3 escalation rule, including 2 cohorts: 2×106/kg and 4×106/kg. The primary endpoint was the incidence of dose-limiting toxicities (DLT). The secondary endpoint was the proportion of patients achieving an objective response. Results 13 participants received anti-CD7 CAR-T cells infusions. No DLT was found. Adverse events included cytokine release syndrome grade 1-2 occurred in 92.3% of patients (n=12), neurotoxicity grade 1-2 in 7.7% (n=1), cytopenia grade 3-4 in 100% (n=13), and viral activation in 69.2% (n=9). All adverse events were reversible. 84.6% (n=11) achieved CR/CRi with 7 patients bridging to stem-cell transplantation. For 2 patients who did not achieve CR/CRi, 1 participant with FLT3/ITD mutation progressed soon without CAR-T cell expansion,1 participant had no response to treatment. At a median follow-up of 4.7 months (range 1.0-43.7), 4 remained in remission, and 7 patients experienced CD7-negative disease relapse. CAR-T cells expanded in 92.3% of patients (n=12). After CAR-T cells infusion, patients' CD7-positive normal T cells were depleted, and CD7-negative T cells expanded dramatically. Conclusions In this first-in-human study of anti-CD7 CAR-T cells for R/R AML, anti-CD7 CAR-T cells exhibited promising efficacy and safety, supporting CD7 CAR-T cell therapy is feasible and efficient for patients with R/R AML. A phase II trial of anti-CD7 CAR-T cells in larger patient cohorts is needed.