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Review
. 2020 Oct 30;10(10):107.
doi: 10.1038/s41408-020-00376-1.

New directions for emerging therapies in acute myeloid leukemia: the next chapter

Naval Daver  1 , Andrew H Wei  2 , Daniel A Pollyea  3 , Amir T Fathi  4 , Paresh Vyas  5 , Courtney D DiNardo  6
Affiliations
Review

New directions for emerging therapies in acute myeloid leukemia: the next chapter

Naval Daver et al. Blood Cancer J. .

Abstract

Conventional therapy for acute myeloid leukemia is composed of remission induction with cytarabine- and anthracycline-containing regimens, followed by consolidation therapy, including allogeneic stem cell transplantation, to prolong remission. In recent years, there has been a significant shift toward the use of novel and effective, target-directed therapies, including inhibitors of mutant FMS-like tyrosine kinase 3 (FLT3) and isocitrate dehydrogenase (IDH), the B-cell lymphoma 2 inhibitor venetoclax, and the hedgehog pathway inhibitor glasdegib. In older patients the combination of a hypomethylating agent or low-dose cytarabine, venetoclax achieved composite response rates that approximate those seen with standard induction regimens in similar populations, but with potentially less toxicity and early mortality. Preclinical data suggest synergy between venetoclax and FLT3- and IDH-targeted therapies, and doublets of venetoclax with inhibitors targeting these mutations have shown promising clinical activity in early stage trials. Triplet regimens involving the hypomethylating agent and venetoclax with FLT3 or IDH1/2 inhibitor, the TP53-modulating agent APR-246 and magrolimab, myeloid cell leukemia-1 inhibitors, or immune therapies such as CD123 antibody-drug conjugates and programmed cell death protein 1 inhibitors are currently being evaluated. It is hoped that such triplets, when applied in appropriate patient subsets, will further enhance remission rates, and more importantly remission durations and survival.

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Conflict of interest statement

A.H.W.: Honoraria from Amgen, Servier, Novartis, Celgene, AbbVie/Genentech, Roche, Pfizer, Janssen Oncology; consulting or advisory role for Servier, Novartis, Amgen, AbbVie/Genentech; speakers’ bureau for AbbVie/Genentech, Novartis; research funding from Novartis (institution), Celgene (institution); former employee of Walter and Eliza Hall Institute, which receives milestone and royalty payments related to venetoclax, and Dr Wei is eligible for benefits related to these payments. D.A.P.: Consulting or advisory role for Celyad, Pfizer, AbbVie, Gilead, Astellas, Forty Seven, Daiichi Sankyo, Celgene, Janssen, Takeda, Amgen; research funding from AbbVie and Pfizer. A.T.F.: Consulting or advisory role for Agios, Seattle Genetics, Forty Seven, Amphivena, AbbVie, Amgen, Astellas, Celgene (BMS), Clear Creek Bio, Trovagene, Novartis, Daiichi Sankyo, Takeda; clinical trial support from Takeda, Celgene, Exelixis, Seattle Genetics. P.V.: Consulting or advisory role for Celgene, Novartis, Jazz, Agios, Pfizer, AbbVie, Astellas, Daiichi Sankyo, Janssen, Takeda; research funding from Celgene, Novartis; scientific advisory board for Auron; co-founder, Oxstem Oncology. C.D.DiNardo: Consulting or advisory role for AbbVie, Agios, Celgene, Daiichi Sankyo, Jazz, Notable Labs; research funding from AbbVie, Agios, Celgene, Daiichi Sankyo, Calithera, Clear Creek Bio. N.D.: Research funding from Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Karyopharm, Servier, Genentech, ImmunoGen, Novimmune, Incyte, AbbVie, Astellas, Forty Seven; consulting or advisory role for Daiichi Sankyo, Bristol-Myers Squibb, Pfizer, Novartis, Celgene, AbbVie, Agios, Astellas, Genentech, Immunogen, Jazz, Forty Seven, Trovagene, Gilead.

Figures

Fig. 1
Fig. 1. Newly diagnosed AML: advancements in the diagnostic and treatment paradigm.
7 + 3, 7 days of standard-dose cytarabine plus 3 days of anthracycline; ADC antibody-drug conjugate; AHD antecedent hematologic disorder; AML acute myeloid leukemia; AML-MRC AML with myelodysplasia-related changes; CBF core binding factor; CLIA cladribine–idarubicin–Ara-C; CPX-351 liposomal formulation of a fixed combination of daunorubicin and cytarabine; GO gemtuzumab ozogamicin; FLAG-Ida fludarabine–Ara-C–filgrastim plus idarubicin; FLT3 FMS-like tyrosine kinase; HMA hypomethylating agent; IDH isocitrate dehydrogenase; LDAC low-dose cytarabine; NGS next-generation sequencing; SCT stem cell transplantation; t-AML therapy-related AML.
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References

    1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA Cancer J. Clin. 2019;69:7–34. doi: 10.3322/caac.21551. - DOI - PubMed
    1. Wiese M, Daver N. Unmet clinical needs and economic burden of disease in the treatment landscape of acute myeloid leukemia. Am. J. Manag. Care. 2018;24:S347–S355. - PubMed
    1. Tallman MS, et al. Acute myeloid leukemia, version 3.2019, NCCN Clinical Practice Guidelines in Oncology. J. Natl Compr. Canc. Netw. 2019;17:721–749. doi: 10.6004/jnccn.2019.0028. - DOI - PubMed
    1. Baudard M, et al. Has the prognosis of adult patients with acute myeloid leukemia improved over years? A single institution experience of 784 consecutive patients over a 16-year period. Leukemia. 1999;13:1481–1490. doi: 10.1038/sj.leu.2401544. - DOI - PubMed
    1. Chen KTJ, Gilabert-Oriol R, Bally MB, Leung AWY. Recent treatment advances and the role of nanotechnology, combination products, and immunotherapy in changing the therapeutic landscape of acute myeloid leukemia. Pharm. Res. 2019;36:125. doi: 10.1007/s11095-019-2654-z. - DOI - PMC - PubMed

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