Updates in the Management of Newly Diagnosed Acute Myeloid Leukemia

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Alice S. Mims
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For patients with newly diagnosed acute myeloid leukemia (AML) who are candidates for intensive induction regimens, all therapies include anthracycline- and cytarabine-based backbones. Core-binding factor AML is typically treated with gemtuzumab ozogamicin and 7 + 3 chemotherapy. Patients with FLT3-mutated (ITD or TKD) disease should have midostaurin + 7 + 3 and consolidation, and those with secondary or therapy-related AML should be considered for CPX-351. For patients ineligible for intensive induction regimens, venetoclax has changed the game and should be used in combination with hypomethylating agents or cytarabine. Glasdegib is also approved in combination with low-dose cytarabine. Patients with IDH1/2-mutated disease can be treated with ivosidenib and enasidenib, respectively. Although enasidenib has yet to secure its spot in the up-front setting, data support its use in newly diagnosed AML. An ongoing question in the field concerns how to treat patients with TP53-mutated AML, because most patients do not respond well to currently available therapies and continue to have poor overall outcomes.

Disclosures: Dr. Mims has disclosed receiving consulting fees from AbbVie, Inc., Astellas Pharma US, Inc., Bristol-Myers Squibb Company, Daiichi- Sankyo Co., Genentech, Inc., Jazz Pharmaceuticals Inc., Kura Oncology, Inc., and Syndax.

Correspondence: Alice S. Mims, MD, MS, The Ohio State University, 1800 Cannon Drive, 1120G Lincoln Tower, Columbus, OH 43210. Email: Alice.Mims@osumc.edu
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  • 1.

    Carter JL, Hege K, Yang J, et al. Targeting multiple signaling pathways: the new approach to acute myeloid leukemia therapy. Signal Transduct Target Ther 2020;5:288.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Bross PF, Beitz J, Chen G, et al. Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clin Cancer Res 2001;7:14901496.

  • 3.

    Castaigne S, Pautas C, Terre C, et al. Effect of gemtuzumab ozogamicin on survival of adult patients with de-novo acute myeloid leukaemia (ALFA-0701): a randomised, open-label, phase 3 study. Lancet 2012;379:15081516.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Burnett AK, Russell NH, Hills RK, et al. A comparison of clofarabine with ara-C, each in combination with daunorubicin as induction treatment in older patients with acute myeloid leukaemia. Leukemia 2017;31:310317.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 5.

    Amadori S, Suciu S, Stasi R, et al. Sequential combination of gemtuzumab ozogamicin and standard chemotherapy in older patients with newly diagnosed acute myeloid leukemia: results of a randomized phase III trial by the EORTC and GIMEMA consortium (AML-17). J Clin Oncol 2013;31:44244430.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 6.

    Hills, RK, Castaigne S, Appelbaum FR, et al. Addition of gemtuzumab ozogamicin to induction chemotherapy in adult patients with acute myeloid leukaemia: a meta-analysis of individual patient data from randomised controlled trials. Lancet Oncol 2014;15:986996.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 7.

    US Food and Drug Administration. FDA approves gemtuzumab ozogamicin for CD33-positive AML. Accessed September 23, 2021. Available at https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-gemtuzumab-ozogamicin-cd33-positive-aml

    • Search Google Scholar
    • Export Citation
  • 8.

    Stone RM, Mandrekar SJ, Sanford BL, et al. Midostaurin plus chemotherapy for acute myeloid leukemia with a FLT3 mutation. N Engl J Med 2017;377:454464.

  • 9.

    Lancet JE, Uy GL, Cortes JE, et al. CPX-351 (cytarabine and daunorubicin) liposome for injection versus conventional cytarabine plus daunorubicin in older patients with newly diagnosed secondary acute myeloid leukemia. J Clin Oncol 2018;36:26842692.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    DiNardo CD, Jonas BA, Pullarkat V, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med 2020;383:617629.

  • 11.

    Venugopal S, Shoukier M, Konopleva M, et al. Outcomes in patients with newly diagnosed TP53-mutated acute myeloid leukemia with or without venetoclax-based therapy. Cancer 2021;127:35413551.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Wei AH, Montesinos P, Ivanov V, et al. Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: a phase 3 randomized placebo-controlled trial. Blood 2020;135:21372145.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13.

    Cortes JE, Heidel FH, Hellmann A, et al. Randomized comparison of low dose cytarabine with or without glasdegib in patients with newly diagnosed acute myeloid leukemia or high-risk myelodysplastic syndrome. Leukemia 2019;33:379389.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Roboz GJ, DiNardo CD, Stein EM, et al. Ivosidenib induces deep durable remissions in patients with newly diagnosed IDH1-mutant acute myeloid leukemia. Blood 2020;135:463471.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 15.

    Tallman MS, Pollyea DA, Altman JK, et al. NCCN Clinical Practice Guidelines in Oncology: Acute Myeloid Leukemia. Version 3. 2021. Accessed October 6, 2021. To view the most recent version, visit NCCN.org

    • Search Google Scholar
    • Export Citation
  • 16.

    Papaemmanuil E, Gerstung M, Bullinger L, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med 2016;374:22092221.

  • 17.

    Eisfeld AK, Mrózek K, Kohlschmidt J, et al. The mutational oncoprint of recurrent cytogenetic abnormalities in adult patients with de novo acute myeloid leukemia. Leukemia 2017;31:22112218.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
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