In a Chinese study reported in The New England Journal of Medicine, Hu et al found that sequential CD7 chimeric antigen receptor (CAR) T-cell therapy and allogeneic hematopoietic stem cell transplantation (HSCT) without graft-vs-host disease (GVHD) prophylaxis was effective in patients with relapsed or refractory CD7-positive leukemia or lymphoma.
Study Details
A total of 10 patients with CD7-positive disease were enrolled in the study between November 2021 and September 2023, including 7 with acute myeloid leukemia, 2 with T-cell acute lymphoblastic leukemia, and 1 with T-cell lymphoblastic lymphoma. Patients received CD7 CAR T-cell infusion at 2 × 106 cells/kg haploidentical CD7 CAR T cells (n = 9) or 5 × 106 cells/kg universal CD7 CAR T cells (n = 1). All patients had been heavily pretreated, with a median of 9.5 prior courses of therapy. Patients who achieved complete remission with incomplete hematologic recovery received haploidentical HSCT without myeloablation or GVHD prophylaxis.
Key Findings
After CAR T-cell therapy, all 10 patients had complete remission with incomplete hematologic recovery. All patients had grade 4 pancytopenia, which was relieved following HSCT. After HSCT, eight patients had full donor chimerism, one had autologous hematopoiesis, and one died on day 13 of septic shock and encephalitis.
Acute GVHD occurred in four patients, one with grade 2 GVHD related to CAR T-cell therapy and three with short-term grade 2 HSCT-related GVHD. No chronic GVHD was observed.
Median follow-up after CAR T-cell therapy was 15.1 months (range = 3.1–24.0 months). In addition to the patient who died on day 13, six patients remained in measurable residual disease–negative complete remission, two had relapse of CD7-negative leukemia, and one died of disease progression at 4.6 months. Estimated 1-year overall survival was 68% (95% confidence interval [CI] = 43%–100%), and estimated 1-year disease-free survival was 54% (95% CI = 29%–100%).
Cytokine-release syndrome occurred in nine patients, grade 1 in five of them and grade 2 in four. No cases of immune effector cell–associated neurotoxicity syndrome were observed. Bacterial or fungal infections of any grade occurred in five patients. Reactivation of Epstein-Barr virus or cytomegalovirus was detected in nine patients.
The investigators concluded: “Our findings suggest that sequential CD7 CAR T-cell therapy and haploidentical HSCT is safe and effective, with remission and serious but reversible adverse events. This strategy offers a feasible approach for patients with CD7-positive tumors who are ineligible for conventional allogeneic HSCT.”
He Huang, MD, PhD, of the Bone Marrow Transplantation Center, First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, is a corresponding author of The New England Journal of Medicine article.
Disclosure: The study was funded by the National Natural Science Foundation of China and the Key Project of Science and Technology Department of Zhejiang Province. For full disclosures of the study authors, visit nejm.org.
