CD7 CAR-T cell therapy based on “Natural Selection” for the treatment of Relapsed or Refractory CD7-positive Hematologic Malignancies: A large cohort study

Abstract

Abstract Background Relapsed or refractory (R/R) hematologic malignancies, including T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL), remain a therapeutic challenge due to limited treatment options and poor clinical outcomes. Chimeric antigen receptor (CAR) T-cell therapy has emerged as a promising immunotherapeutic approach for hematologic malignancies. Previous studies have demonstrated that autologous anti-CD7 CAR-T cells generated using the “Natural Selection” (NS) platform (NS7CAR) exhibit manageable toxicity profiles and good efficacy in patients with R/R T-ALL/LBL and CD7-positive acute myeloid leukemia (AML). This pooled analysis evaluates the efficacy and safety of NS7CAR-T therapy based on data from 5 clinical trials (https://clinicaltrials.gov, NCT04572308, NCT05626400, NCT04916860, NCT04928105, and NCT04938115) involving patients with CD7-positive hematologic malignancies. Methods This study represents a pooled, cohort analysis of subjects enrolled in clinical trials evaluating NS7CAR therapy. Eligible participants included patients with R/R CD7-positive hematologic malignancies who received at least one infusion of autologous NS7CAR-T cells and were observed between November 9, 2020, and May 21, 2025. Baseline demographic and clinical characteristics, CAR-T cell dosing, and post-infusion outcomes were systematically collected. Efficacy and safety assessments included overall response rates (ORR), overall survival (OS), progression-free survival (PFS), and the incidence of adverse events. Descriptive statistics were used to summarize key variables. Results The analysis included a total of 334 patients with R/R CD7-positive hematologic malignancies. The cohort comprised 159 cases (47.6%) of T-ALL and 121 cases (36.2%) of T-LBL, mixed phenotype acute leukemia accounted for 24 cases (7.2%), AML for 21 cases (6.3%), and peripheral T-cell lymphoma (PTCL) for 9 cases (2.7%). The median age was 24 years (range: 2–67 years), with 255 males (76.3%) and 79 females (23.7%). At enrollment, 88 patients (26.3%) were relapsed from prior transplants, including 4 patients who relapsed after 2nd transplants. The median time to relapse post-transplantation was 265 days (range: 31-2432 days). Regarding baseline disease involvement before NS7CAR-T infusion, 128 patients (38.3%) showed isolated bone marrow (BM) involvement, 56 patients (16.8%) presented with isolated extramedullary disease (EMD), and the remaining 137 patients (41.0%) demonstrated concurrent involvements of both BM and EMD. Among those with BM involvement, 29.8% (79/265) had ≥20% blasts. Patients received three dose levels of NS7CAR-T cells, 15.3% (51/334) of 5×10⁵ cells/kg, 83.2% (278/334) of 1×10⁶ cell/kg, and 1.5% (5/334) of 1.5–2×10⁶ cells/kg. The median dose of NS7CAR-T cell infusion administered to patients was 1×10⁶ cells/kg. After NS7CAR-T therapy, among 329 evaluable patients as of August 1, 2025, the ORR reached 86.3% (284/329), with a complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate of 84.5% (278/329). Post-treatment evaluation revealed that 245 patients (73.4%) underwent consolidation/salvage transplantation following CAR-T therapy, with a median interval of 57 days (range: 28-227 days) between CAR-T infusion and transplantation. Survival analysis demonstrated a median PFS of 547.5 days (range: 45-1694 days) and median OS of 567.5 days (range: 45-1694 days). Safety assessment of the full cohort (n=334) showed cytokine release syndrome (CRS) occurring in 95.8% of patients (320/334), with the majority (85.6%, 286/334) experiencing grade 1-2 events and 10.2% (34/334) developing grade ≥3 CRS. Immune effector cell-associated neurotoxicity syndrome (ICANS) was observed in 3.3% of cases (11/334), including 0.9% (3/334) with grade 1-2 and 2.4% (8/334) with grade ≥3. Conclusions This large pooled cohort analysis demonstrates that NS7CAR-T therapy exhibits very promising clinically efficacy, achieving an 84.5% CR rate, along with a manageable safety profile in patients with R/R CD7-positive hematologic malignancies, including T-ALL/LBL, AML, MPAL and PTCL. While a small subset of patients experienced grade ≥3 CRS and ICANS, the robust response rates and survival outcomes position NS7CAR-T as a potentially transformative treatment option for R/R CD7-positive hematologic malignancies, including post-transplant relapsed patients.