Donor-derived CD19 CAR-T cell therapy of relapse of CD19-positive B-ALL post allotransplant

Leukemia. 2021 Jun;35(6):1563-1570. doi: 10.1038/s41375-020-01056-6. Epub 2020 Oct 19.

Abstract

Safety and efficacy of allogeneic anti-CD19 chimeric antigen receptor T cells (CAR-T cells) in persons with CD19-positive B-cell acute lymphoblastic leukemia (B-ALL) relapsing after an allotransplant remain unclear. Forty-three subjects with B-ALL relapsing post allotransplant received CAR-T cells were analyzed. 34 (79%; 95% confidence interval [CI]: 66, 92%) achieved complete histological remission (CR). Cytokine release syndrome (CRS) occurred in 38 (88%; 78, 98%) and was ≥grade-3 in 7. Two subjects died from multiorgan failure and CRS. Nine subjects (21%; 8, 34%) developed ≤grade-2 immune effector cell-associated neurotoxicity syndrome (ICANS). Two subjects developed ≤grade-2 acute graft-versus-host disease (GvHD). 1-year event-free survival (EFS) and survival was 43% (25, 62%). In 32 subjects with a complete histological remission without a second transplant, 1-year cumulative incidence of relapse was 41% (25, 62%) and 1-year EFS and survival, 59% (37, 81%). Therapy of B-ALL subjects relapsing post transplant with donor-derived CAR-T cells is safe and effective but associated with a high rate of CRS. Outcomes seem comparable to those achieved with alternative therapies but data from a randomized trial are lacking.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Antigens, CD19 / metabolism*
  • Child
  • Child, Preschool
  • Female
  • Follow-Up Studies
  • Hematopoietic Stem Cell Transplantation / mortality*
  • Humans
  • Immunotherapy, Adoptive / methods*
  • Male
  • Middle Aged
  • Neoplasm Recurrence, Local / metabolism
  • Neoplasm Recurrence, Local / pathology
  • Neoplasm Recurrence, Local / therapy*
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / immunology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / metabolism
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / pathology
  • Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / therapy*
  • Prognosis
  • Receptors, Chimeric Antigen / immunology
  • Retrospective Studies
  • Survival Rate
  • Tissue Donors
  • Transplantation, Homologous
  • Young Adult

Substances

  • Antigens, CD19
  • Receptors, Chimeric Antigen