A Single-Arm, Open-Label, Pilot Trial of Autologous CD7-CAR-T Cells for CD7 Positive Relapsed and Refractory T-Lymphoblastic Leukemia/Lymphoma

Abstract Introduction: T lymphoblastic leukemia/lymphoma (T-ALL/LBL) is highly aggressive. Although intensive chemotherapies such as ALL-type regimens are commonly used, about half patients eventually relapse and die of T-ALL/LBL. Chimeric antigen receptor (CAR) T cells have given rise to breakthroughs in treating B cell hematological malignancies. However, there are few clinical studies of CAR-T on T cell malignant tumors. CD7, overexpressed in up to 100% of relapsed/refractory T-ALL/LBL, is an attractive therapeutic target for T-lymphoblastic leukemia/lymphoma (T-ALL/LBL). Although several healthy donor derived CD7-CAR-T trials have been reported, autologous CD7-CAR-T cell therapy represents another promising strategy. In current study, a nanobody derived autologous CD7-CAR-T with a highly optimized structure and a clinically feasible strategy to overcome CAR-T cell fratricide and exclude abnormal T cell contamination have been developed. Method This is a single-arm, open label, safety and efficacy pilot study (NCT04004637). Study participants will receive Flu/Cy pre-treatment before CAR-T infusion. CD7 CAR-T was then administered at a single dose of 1.0x10 6 (N=5) or 1.5x10 6 (N=1; Pt#1) or 2x10 6 (N=3; Pt#7, 8,) CAR-T cells/kg. Adverse events were categorized by NCI-CTCAE V5.0. Tumor responses were assessed based on the 2014 Lugano Evaluation Criteria for Lymphoma and 2016 Chinese Guideline for Diagnosis and Treatment of Acute Lymphoblastic Leukemia. Results: Total of 8 patients including 5 r/r T-ALL/LBL and 3 r/r ETP-ALL/LBL (case 4, 5, 6) were assigned to receive CD7 CAR-T cell and completed the efficacy assessment. Overall response rate at 1 month was 100%. In patients followed up for ≥ 3 months, complete remission (CR) rate at 3 month was 75%. Case 1-6 was administered at 1.0×10 6 CAR-T/Kg except for case 1 (1.0×10 6 CAR-T/Kg). Bone marrow (BM) tumor burden of case 1 decreased from 70.03% to 19.51% and case 1 has an OS for nearly two years. Case 2 died due to abdominal infection at 3 month although he was still in MRD- status then. Case 3 had sustained MRD- for 7 months but appeared MRD+ in BM at 8 month, so second CD7 CAR-T infusion had been performed and achieved CR at 14th day again. Case 4 has been achieving CR 12 months. Case 5 and 6 had a DOR (Duration of response) of about 3 and 2 months respectively. In case 1-6, despite case1-2 appeared grade 2 CRS, all other cases only had grade 1. Therefore, in order to further explore the best effective dose, case 7-8 had received dose of 2.0×10 6 CAR-T/Kg. Case 8 are still in complete remission. Unfortunately, case 7 relapsed at 6 month due to CD7 negative blasts. The absence of CD7 on the cell surface enables the tumor to evade CAR T cell-mediated recognition and clearance, despite continued persistence of CAR-T cells. Conclusions: Autologous CD7 CAR-T represents a promising immunotherapy for r/r T-ALL/LBL and exhibited encouraging clinical efficacy and safety in treating r/r T-ALL/LBL and ETP-ALL/LBL. Figure 1Figure 1. Disclosures No relevant conflicts of interest to declare.