CAR T-Cell Therapy Appeared Safe, With No Signs of GVHD in Patients With T-Cell Lymphoma/Leukemia

A study presented at the 2022 American Society of Clinical Oncology Annual Meeting found that an autologous CD7 chimeric antigen receptor (CAR) T-cell therapy was effective for patients with relapsed/refractory T-cell acute lymphoblastic leukemia and lymphoma (ALL/LBL), with no signs of graft-versus-host disease (GVHD) reported.

The phase I study included patients with CD7+ relapsed/refractory T-cell ALL/LBL with no leukemic cells in the peripheral blood. Following a “3+3” dose escalation process, the CD7 CAR construct included an endoplasmic reticulum anchor domain fused to a CD7 binding domain to prevent CD7 expression on cell surface, which contributed to minimizing CAR T-cell fratricide. CAR T product was checked to ensure lack of tumor contamination before infusion.

Between September 2021 and January 2022, 5 patients (median age, 3.8 years; range, 1.9-13.0 years) were enrolled in the study. Of those patients, 1 had mediastinal mass and blasts in pleural fluid, 1 had central nervous system-3 status, and 3 had marrow disease with a median burden of 1.35% (range, 0.07%-7.31%).

Patients received CAR T-cell therapy at the following doses: 5 × 105 cells/kg (n = 3) and 1 × 106 cells/kg (n = 1). One patient received cells below the target dose.

A total of 3 patients had cytokine release syndrome (CRS), and 1 patient experienced grade 3 CRS. Median onset to CRS was 5 days (range, 1-9 days), with a median duration of 4 days (range, 3-14 days). There were no reports of neurotoxicity, GVHD, or infection.

All patients experienced grade 3/4 hematologic toxicities, which recovered to grade 2 within 30 days.

At 1 month post-infusion, 4 patients achieved complete remission, and 1 patient still had leukemia cells in the cerebrospinal fluid. At a median follow-up of 62 days (range, 35-136 days), 1 patient underwent hematopoietic stem cell transplantation (HSCT) at 2.9 months post-infusion and had a CD7‒ relapse at 1.4 months post-HSCT. The other 3 patients who experienced a response were in minimal residual disease-negative complete remission.

In the 4 patients who received target dose, the median peak CAR T-cell count in peripheral blood was 4.27 × 102/µL (range, 2.49-5.61) by flow cytometry. All patients had detectable CAR transgene by polymerase chain reaction at their last visits.

Longer follow-up with more patients is needed to further evaluate this CAR T-cell therapy, the researchers noted.

 

Zhao L, Pan J, Tang K, et al. Autologous CD7-targeted CAR T-cell therapy for refractory or relapsed T-cell acute lymphoblastic leukemia/lymphoma. Abstract #7035. Presented at the 2022 American Society of Clinical Oncology Annual Meeting; June 3-7, 2022; Chicago, IL.