Allogeneic CD5-specific CAR-T therapy for relapsed/refractory T-ALL: a phase 1 trial.

Area of Science:

• Oncology
• Immunotherapy
• Hematology

Background:

• Refractory or relapsed T-cell acute lymphoblastic leukemia (r/r T-ALL) has a poor prognosis due to limited effective salvage therapies.
• CD7-targeting chimeric antigen receptor (CAR)-T therapies show promise but are often limited by antigen loss and subsequent relapse.

Purpose of the Study:

• To evaluate the safety and efficacy of a CD5-gene-edited CAR-T cell therapy in patients with r/r T-ALL.
• To assess the potential of CD5-targeting CAR-T cells in patients who previously failed CD7 CAR-T therapy.

Main Methods:

• A total of 19 patients with r/r T-ALL were enrolled, with CAR-T products derived from either previous transplant donors or new matched donors.
• Patients received infusions, with primary endpoints including dose-limiting toxicity and adverse events within 30 days.
• Secondary endpoints focused on treatment response, CAR-T cell pharmacokinetics, and long-term adverse events.

Main Results:

• All patients (100%) achieved complete remission or complete remission with incomplete blood count recovery by day 30.
• CAR-T cells persisted and effectively cleared CD5-positive T-cells, with CD5-negative T-cells increasing but remaining below normal levels.
• Grade 3-4 cytopenias were common, and one patient experienced a grade 3 infection within 30 days; consolidative transplantation was associated with better outcomes in some patients.

Conclusions:

• CD5-specific CAR-T cell therapy demonstrates a high remission rate for T-ALL patients, offering a viable option for those refractory to or relapsed after prior treatments.
• Gene editing to target CD5 appears effective in overcoming antigen escape mechanisms seen with CD7-targeting therapies.
• Consolidative transplantation following CAR-T therapy may be crucial for mitigating the risk of late-onset severe infections and improving long-term outcomes in r/r T-ALL.