In a Chinese single-institution phase I study reported in the Journal of Clinical Oncology, Pan et al found that donor-derived CD7 chimeric antigen receptor (CAR) T-cell therapy produced a high complete remission rate in patients with relapsed or refractory T-cell acute lymphoblastic leukemia (T-ALL).
Study Details
Twenty patients from Beijing Boren Hospital were enrolled into the trial between July and December 2020. They received anti-CD7 CAR T cells manufactured from either previous stem cell transplantation donors or new donors in single infusions of 5 x 105 or 1 x 106 cells/kg.
Toxicity
No dose-limiting toxicities were observed. All patients (100%) had cytokine-release syndrome, which was grade 3 or 4 in 10%; grade 3 or 4 cytopenias also occurred in all patients (100%). Neurotoxicity occurred in 15%, graft-vs-host disease in 60%, and viral activation in 20%, with all these events being grade 1 or 2. Adverse events led to death in one patient (due to pulmonary hemorrhage related to fungal pneumonia at 5.5 months postinfusion).
KEY POINTS
- Donor-derived CD7 CAR T-cell therapy led to complete remission in 90% of patients.
- At median follow-up of 6 months, 75% of patients remained in remission.
Responses
Response was observed in 19 patients (95%), with complete remission in 18 (90%), including 17 (85%) with minimal residual disease–negative complete remission by day 15 postinfusion. A total of seven patients underwent stem cell transplantation. At a median follow-up of 6.3 months (range = 4.0–9.2 months), 15 patients remained in remission, including 6 of 7 who underwent stem cell transplantation and 9 of 11 who received no additional treatment for their leukemia.
CAR T cells were detectable in each of the five patients evaluated at 6 months postinfusion. Infusion resulted in rapid depletion of CD7-positive normal lymphocytes—including T cells—within 15 days, with a dramatic increase in CD7-negative T cells observed in all patients. T cells exhibited an effector or effector memory phenotype with a minimal naive fraction. The investigators noted that the expansion of CD7-negative T cells may have alleviated treatment-related T-cell immunodeficiency.
The investigators concluded, “Among 20 patients with relapsed or refractory T-ALL enrolled in this trial, donor-derived CD7 CAR T cells exhibited efficient expansion and achieved a high complete remission rate with [a] manageable safety profile. A multicenter, phase II trial of donor-derived CD7 CAR T cells is in progress.”
Jing Pan, MD, of Boren Clinical Translational Center, Beijing Boren Hospital, is the corresponding author for the Journal of Clinical Oncology article.
Disclosure: The study was supported by the National Key R&D Program of China, Non-Profit Central Research Institute Fund of Chinese Academy of Medical Sciences, and others. For full disclosures of the study authors, visit ascopubs.org.
