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

Clin Cancer Res. 2021 Mar 1;27(5):1242-1246. doi: 10.1158/1078-0432.CCR-20-1271. Epub 2020 Nov 24.

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-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.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antigens, CD7 / immunology*
  • Clinical Trials as Topic
  • Cytokine Release Syndrome / drug therapy*
  • Cytokine Release Syndrome / etiology
  • Cytokine Release Syndrome / pathology
  • Humans
  • Immunotherapy, Adoptive / adverse effects*
  • Male
  • Nitriles / therapeutic use*
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor T-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Pyrazoles / therapeutic use*
  • Pyrimidines / therapeutic use*
  • Young Adult

Substances

  • Antigens, CD7
  • Nitriles
  • Pyrazoles
  • Pyrimidines
  • ruxolitinib