Eradication of T-ALL Cells by CD7-targeted Universal CAR-T Cells and Initial Test of Ruxolitinib-based CRS Management

Purpose: Although chimeric antigen receptor T-cell (CAR-T) therapy development for B-cell malignancies has made significant progress in the last decade, broadening the success to treating T-cell acute lymphoblastic leukemia (T-ALL) has been limited. We conducted two clinical trials to verify the safety and efficacy of GC027, an off-the-shelf allogeneic CAR-T product targeting T-cell antigen, CD7. Here, we report 2 patients as case reports with relapsed/ refractory T-ALL who were treated with GC027. Patients and Methods: Both the trials reported here were open-label and single-arm. A single infusion of GC027 was given to each patient after preconditioning therapy. Result: Robust expansion of CAR-T cells along with rapid eradication of CD7(+) T lymphoblasts were observed in the peripheral blood, bone marrow, and cerebrospinal fluid. Both patients achieved complete remission with no detectable minimal residual disease. At data cutoff, 30 September 2020, 1 of the 2 patients remains in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome (CRS) occurred in both patients and was managed by a novel approach with a ruxolitinib-based CRS management. Ruxolitinib showed promising activity in a preclinical study conducted at our center. No graft-versus-host disease was observed. Conclusions: The two case reports demonstrate that a standalone therapy with this novel CD7-targeted off-the-shelf allogeneic CAR-T therapy may provide deep and durable responses in select patients with relapsed/refractory T-ALL. GC027 might have a potential to be a promising new approach for treating refractory/ relapsed T-ALL. Further studies are warranted.

Automated summary

The study reports two cases of patients with relapsed/refractory T-ALL treated with GC027, showing robust expansion of CAR-T cells and rapid eradication of CD7(+) T lymphoblasts. Both patients achieved complete remission with no minimal residual disease. One patient remained in ongoing remission for over 1 year after CAR T-cell infusion. Grade 3 cytokine release syndrome occurred in both patients and was managed with a novel approach using ruxolitinib. No graft-versus-host disease was observed. These findings suggest that GC027 may be a promising new approach for treating refractory/relapsed T-ALL. Further studies are needed.