Immunotherapy for acute myeloid leukemia: from allogeneic stem cell transplant to novel therapeutics

Leuk Lymphoma. 2019 Dec;60(14):3350-3362. doi: 10.1080/10428194.2019.1639167. Epub 2019 Jul 23.

Abstract

Immunotherapy in the form of allogeneic stem cell transplantation (SCT) plays an instrumental role in the treatment of acute myeloid leukemia (AML), with non-transplant modalities of immunotherapy including checkpoint blockade now being actively explored. Here, we provide an overview of the graft versus leukemia (GVL) effect in AML as a window into understanding the prospects of AML immunotherapy. We explore the roles of various cell types in orchestrating anti-leukemic immunity, as well as those contributing to the unique immune suppressive state of myeloid diseases. We discuss specific approaches to engage the immune system, while noting the challenges of the AML antigen landscape and the barriers to immune modulation. We review the potential for immunomodulatory agents in combination with cellular therapies, donor lymphocyte infusion, and following SCT. Finally, to address the challenge of minimal residual disease (MRD) following chemotherapy, we propose combination epigenetic and immunotherapy for the eradication of MRD.

Keywords: AML; Immunotherapy; T cells; antibodies; checkpoint blockade; neoantigen; vaccines.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Cell- and Tissue-Based Therapy / methods*
  • Combined Modality Therapy
  • Hematopoietic Stem Cell Transplantation / methods*
  • Humans
  • Immunotherapy / methods*
  • Leukemia, Myeloid, Acute / therapy*
  • Neoplasm, Residual / prevention & control*
  • Prognosis