Eradication of T-ALL cells by CD7 targeted universal CAR-T cells and initial test of ruxolitinib-based CRS management

Abstract

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-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 two patients as case reports with relapsed/refractory T-ALL who were treated with GC027. Experimental Design：Both of the two trials reported are open-labeled 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 (CR) with no minimal residual disease (MRD) detectable. At data cut off Sep.30, 2020 one of the two patients remains in ongoing remission for over one 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 (GvHD) was observed. Conclusion：The two case reports demonstrate that a stand alone therapy with this novel CD7 targeted "off-the-shelf" allogeneic CAR-T therapy may provide deep and durable responses in select r/r T-ALL patients. GC027- might have a potential to be a promising new approach for treating refractory/relapsed T - ALL. Further studies are warranted.