At the 67th Annual Meeting of the American Society of Hematology (ASH), Professor Lu Peihua and Professor Zhang Xian from Lu Daopei Hospital presented a large-scale clinical study of a CD7 CAR-T therapy developed on the “Natural Selection” platform in patients with relapsed or refractory (R/R) CD7-positive hematologic malignancies. The study not only confirmed the broad applicability of NS7CAR-T across T-ALL/LBL, AML, MPAL, and PTCL, but also provided an innovative therapeutic option for patients with post-transplant relapse. These findings carry potentially transformative clinical value and offer important evidence to support future optimization of treatment strategies and precision management.Title CD7 CAR-T Cell Therapy Based on “Natural Selection” for the Treatment of Relapsed or Refractory CD7-Positive Hematologic Malignancies: A Large Cohort Study
Chinese Title 基于“自然选择”平台的CD7 CAR-T细胞治疗复发/难治性CD7阳性血液系统恶性肿瘤：一项大样本队列研究
First Author Zhang Xian
Corresponding Author Lu Peihua
Study Background
Relapsed or refractory hematologic malignancies, including T-cell acute lymphoblastic leukemia/lymphoblastic lymphoma (T-ALL/LBL), remain a major therapeutic challenge due to limited treatment options and poor clinical prognosis. Chimeric antigen receptor T-cell (CAR-T) therapy has emerged as a promising immunotherapeutic approach. Previous studies have shown that autologous anti-CD7 CAR-T cells manufactured using the “Natural Selection” (NS) platform (NS7CAR) demonstrate manageable toxicity profiles and favorable efficacy in patients with R/R T-ALL/LBL and CD7-positive acute myeloid leukemia (AML). The present study provides a pooled analysis of efficacy and safety data from CD7-positive hematologic malignancy patients treated with NS7CAR-T across five clinical trials (registration numbers: NCT04572308, NCT05626400, NCT04916860, NCT04928105, and NCT04938115).
Methods
This study was a pooled cohort analysis that included patients with R/R CD7-positive hematologic malignancies who received at least one infusion of autologous NS7CAR-T cells in the aforementioned clinical trials. The observation period spanned from November 9, 2020, to May 21, 2025. Baseline demographic and clinical characteristics, CAR-T cell doses, and post-infusion outcomes were systematically collected. Efficacy and safety endpoints included overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and the incidence of adverse events.
Results
A total of 334 patients with R/R CD7-positive hematologic malignancies were included, comprising 159 cases of T-ALL (47.6%), 121 cases of T-LBL (36.2%), 24 cases of mixed phenotype acute leukemia (7.2%), 21 cases of AML (6.3%), and 9 cases of peripheral T-cell lymphoma (2.7%). The median age was 24 years (range, 2–67 years), with 255 males (76.3%) and 79 females (23.7%). Eighty-eight patients (26.3%) experienced relapse after prior transplantation, including four cases of relapse after a second transplant. Among patients with bone marrow involvement, 29.8% (79/265) had ≥20% blasts. Patients received three different dose levels of NS7CAR-T cells, with a median dose of 1×10⁶ cells/kg.
As of August 1, 2025, among 329 evaluable patients, the ORR was 86.3% (284/329), and the complete remission/complete remission with incomplete hematologic recovery (CR/CRi) rate was 84.5% (278/329). Following CAR-T therapy, 245 patients (73.4%) underwent consolidative or salvage transplantation, with a median interval of 57 days (range, 28–227 days). The median PFS was 547.5 days (range, 45–1694 days), and the median OS was 567.5 days (range, 45–1694 days). Safety analyses showed a cytokine release syndrome (CRS) incidence of 95.8% (320/334), with 85.6% being grade 1–2 and 10.2% being grade ≥3. Immune effector cell–associated neurotoxicity syndrome (ICANS) occurred in 3.3% (11/334) of patients, including 0.9% with grade 1–2 events and 2.4% with grade ≥3 events.
Conclusion
This large pooled cohort analysis demonstrates that NS7CAR-T therapy delivers highly promising clinical efficacy with a controllable safety profile in patients with R/R CD7-positive hematologic malignancies, including T-ALL/LBL, AML, MPAL, and PTCL. With a CR/CRi rate as high as 84.5%, and despite the occurrence of grade ≥3 CRS or ICANS in a minority of patients, overall response rates and survival outcomes were highly favorable. These findings suggest that NS7CAR-T therapy may represent a transformative treatment option for patients with R/R CD7-positive hematologic malignancies, including those who relapse after transplantation.
Expert Profiles
Lu Peihua, MD, PhD Lu Daopei Hospital Beijing Lu Daopei Institute of Hematology
Executive Medical Director, Lu Daopei Hospital President, Beijing Lu Daopei Institute of Hematology Graduated from Peking University Health Science Center; completed residency training at the University of Nebraska Medical Center, and subsequently specialized training in hematology and oncology at Stanford University Board-certified hematologist and oncologist in the United States; licensed to practice medicine in both the United States and China Member, 4th Committee of the Department of Oncology, Capital Medical University Standing Director, First Council of the China Association of Non-Public Medical Institutions Chair, Hematology Committee, China Association of Non-Public Medical Institutions Standing Member, Biotechnology and Cell Application Committee, China Association of Non-Public Medical Institutions Member, Expert Committee of the China Marrow Donor Program Standing Member, Anti-Leukemia Expert Committee, Chinese Society of Clinical Oncology (CSCO) Standing Member, Translational Hematology Committee, Chinese Anti-Cancer Association Board Member, 7th Council of the Beijing Medical Education Association Recipient of the 2021 Taishan Award for Value-Based Healthcare Management
Zhang Xian, MD, PhD
Lu Daopei Hospital Hebei Yanda Lu Daopei Hospital
Director, General Hematology and Immunotherapy Department Chief Physician Doctor of Hematology Member, Hematology Physicians Branch of the Chinese Medical Doctor Association Member, Hematopoietic Stem Cell Transplantation and Cell Therapy Group, Hematologic Oncology Committee of the Chinese Anti-Cancer Association Member, Cell Research and Therapy Committee, Chinese Research Hospital Association Expert Panel Member, Human Leukocyte Antigen Committee, Chinese Society of Blood Transfusion Member, Leukemia Immunotherapy Collaborative Group, Chinese Hematology Specialty Alliance Registered Physician, CCPAP Program of the China Charity Federation Member, Hematologic Malignancies Committee, Beijing Anti-Cancer Association Member, Red Blood Cell Disorders Committee, Beijing Society for Cancer Prevention and Treatment Member, Multidisciplinary Lymphoma Committee, Beijing Integrative Medicine Association Member, Lymphoma Committee, Hebei Society of Hematology
