Review
. 2019 Jul; 60(14):3350-3362.
doi: 10.1080/10428194.2019.1639167.

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

David A Knorr 1 Aaron D Goldberg 1 Eytan M Stein 1 Martin S Tallman 1 
Affiliations
  • PMID: 31335250
  •     122 References
  •     1 citations

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.

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Blood, 2001 Dec 12; 98(13). PMID: 11739182
Adoptive transfer of PR1 cytotoxic T lymphocytes associated with reduced leukemia burden in a mouse acute myeloid leukemia xenograft model.
Qing Ma, Changqing Wang, +11 authors, Jeffrey J Molldrem.
Cytotherapy, 2010 Aug 26; 12(8). PMID: 20735170    Free PMC article.
Combination Lenalidomide and Azacitidine: A Novel Salvage Therapy in Patients Who Relapse After Allogeneic Stem-Cell Transplantation for Acute Myeloid Leukemia.
Charles Craddock, Daniel Slade, +11 authors, Christina Yap.
J Clin Oncol, 2019 Jan 18; 37(7). PMID: 30653424    Free PMC article.
Ipilimumab for Patients with Relapse after Allogeneic Transplantation.
Matthew S Davids, Haesook T Kim, +30 authors, Leukemia and Lymphoma Society Blood Cancer Research Partnership.
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Highly Cited.
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Naval Daver, Prajwal Boddu, +4 authors, Hagop Kantarjian.
Leukemia, 2018 Mar 01; 32(5). PMID: 29487386    Free PMC article.
Highly Cited. Review.
Spontaneous remission of acute myeloid leukemia after infection and blood transfusion associated with hypergammaglobulinaemia.
M Mitterbauer, M Fritzer-Szekeres, +12 authors, U Jaeger.
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Mutations Associated with Acquired Resistance to PD-1 Blockade in Melanoma.
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N Engl J Med, 2016 Jul 20; 375(9). PMID: 27433843    Free PMC article.
Highly Cited.
Loss of plasmacytoid dendritic cell differentiation is highly predictive for post-induction measurable residual disease and inferior outcomes in acute myeloid leukemia.
Wenbin Xiao, Aaron D Goldberg, +23 authors, Mikhail Roshal.
Haematologica, 2018 Dec 14; 104(7). PMID: 30523054    Free PMC article.
Current status of vaccination therapy for leukemias.
Volker L Reichardt, Peter Brossart.
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Review.
In acute myeloid leukemia, B7-H1 (PD-L1) protection of blasts from cytotoxic T cells is induced by TLR ligands and interferon-gamma and can be reversed using MEK inhibitors.
Céline Berthon, Virginie Driss, +5 authors, Bruno Quesnel.
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A phase 1 trial of the anti-inhibitory KIR mAb IPH2101 for AML in complete remission.
Norbert Vey, Jean-Henri Bourhis, +9 authors, Daniel Olive.
Blood, 2012 Sep 25; 120(22). PMID: 23002117
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"Natural" killer cells in the mouse. I. Cytotoxic cells with specificity for mouse Moloney leukemia cells. Specificity and distribution according to genotype.
R Kiessling, E Klein, H Wigzell.
Eur J Immunol, 1975 Feb 01; 5(2). PMID: 1234049
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PD-1 blockade with nivolumab in relapsed or refractory Hodgkin's lymphoma.
Stephen M Ansell, Alexander M Lesokhin, +16 authors, Philippe Armand.
N Engl J Med, 2014 Dec 09; 372(4). PMID: 25482239    Free PMC article.
Highly Cited.
Inhibiting DNA Methylation Causes an Interferon Response in Cancer via dsRNA Including Endogenous Retroviruses.
Katherine B Chiappinelli, Pamela L Strissel, +20 authors, Reiner Strick.
Cell, 2015 Sep 01; 162(5). PMID: 26317466    Free PMC article.
Highly Cited.
Acute myeloid leukemia with monosomal karyotype: morphologic, immunophenotypic, and molecular findings.
Olga K Weinberg, Robert S Ohgami, +6 authors, Daniel A Arber.
Am J Clin Pathol, 2014 Jul 13; 142(2). PMID: 25015859
STING Pathway Activation Stimulates Potent Immunity against Acute Myeloid Leukemia.
Emily Curran, Xiufen Chen, +5 authors, Justin Kline.
Cell Rep, 2016 Jun 07; 15(11). PMID: 27264175    Free PMC article.
5-Azacytidine and DLI can induce long-term remissions in AML patients relapsed after allograft.
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Immune Biology of Acute Myeloid Leukemia: Implications for Immunotherapy.
Sophia Khaldoyanidi, Dirk Nagorsen, +2 authors, Marion Subklewe.
J Clin Oncol, 2021 Jan 13; 39(5). PMID: 33434043    Free PMC article.
Review.