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An Update on Immune Based Therapies in Acute Myeloid Leukemia: 2021 and Beyond!

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Immunotherapy

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1342))

Abstract

Despite advances in the treatment of acute myeloid leukemia (AML), relapse is still widely observed and represents the major cause of death among patients with AML. Treatment options in the relapse setting are limited, still relying predominantly on allogeneic hematopoietic stem cell transplantation (allo-HSCT) and cytotoxic chemotherapy, with poor outcomes. Novel targeted and venetoclax-based combinations are being investigated and have shown encouraging results. Immune checkpoint inhibitors in combination with low-intensity chemotherapy demonstrated encouraging response rates and survival among patients with relapsed and/or refractory (R/R) AML, especially in the pre- and post-allo-HSCT setting. Blocking the CD47/SIRPα pathway is another strategy that showed robust anti-leukemic activity, with a response rate of around 70% and an encouraging median overall survival in patients with newly diagnosed, higher-risk myelodysplastic syndrome and patients with AML with a TP53 mutation. One approach that was proven to be very effective in the relapsed setting of lymphoid malignancies is chimeric antigen receptor (CAR) T cells. It relies on the infusion of genetically engineered T cells capable of recognizing specific epitopes on the surface of leukemia cells. In AML, different CAR constructs with different target antigens have been evaluated and demonstrated safety and feasibility in the R/R setting. However, the difficulty of potently targeting leukemic blasts in AML while sparing normal cells represents a major limitation to their use, and strategies are being tested to overcome this obstacle. A different approach is based on endogenously redirecting the patient’s system cells to target and destroy leukemic cells via bispecific T-cell engagers (BiTEs) or dual antigen receptor targeting (DARTs). Early results have demonstrated the safety and feasibility of these agents, and research is ongoing to develop BiTEs with longer half-life, allowing for less frequent administration schedules and developing them in earlier and lower disease burden settings.

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Conflict of Interest

ND reports research funding from Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Karyopharm, Sevier, Genentech, Astellas, AbbVie, Genentech, Novimmune, Amgen, Trovagene, Gilead, FATE therapeutics, Trillium, Hanmi, Newave, Glycomimetics, and ImmunoGen. He has served in a consulting or advisory role for Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Novartis, Celgene, AbbVie, Genentech, Servier, Trillium, Syndax, Trovagene, Astellas, Gilead, STAR therapeutics, KITE, and Agios.

Authorship Contributions

FH and ND analyzed the data, wrote the paper, reviewed and approved the manuscript, and shared final responsibility for the decision to submit.

Funding

This work was supported in part by the MD Anderson Cancer Centre Support Grant (CCSG) CA016672, the MD Anderson Cancer Center Leukemia SPORE CA100632, the Charif Souki Cancer Research Fund, the Dick Clark Immunotherapy Fund, and generous philanthropic contributions to the MD Anderson Moon Shots Program.

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  1. Department of Leukemia, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Fadi Haddad & Naval Daver

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  1. Fadi Haddad
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  2. Naval Daver
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Correspondence to Naval Daver .

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  1. Professor, Dept. of Investigational Cancer Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA

    Aung Naing

  2. Assistant Professor, Service Chief of Adult Allergy & Immunology, Division of Immunology, Allergy & Retrovirology Baylor College of Medicine and Texas Children’ Hospital, Houston, TX, USA

    Joud Hajjar

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Haddad, F., Daver, N. (2021). An Update on Immune Based Therapies in Acute Myeloid Leukemia: 2021 and Beyond!. In: Naing, A., Hajjar, J. (eds) Immunotherapy. Advances in Experimental Medicine and Biology, vol 1342. Springer, Cham. https://doi.org/10.1007/978-3-030-79308-1_9

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