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Review
. 2024 Sep 19;14(1):163.
doi: 10.1038/s41408-024-01143-2.

Current status and research directions in acute myeloid leukemia

Hagop Kantarjian  1 , Gautam Borthakur  2 , Naval Daver  2 , Courtney D DiNardo  2 , Ghayas Issa  2 , Elias Jabbour  2 , Tapan Kadia  2 , Koji Sasaki  2 , Nicholas J Short  2 , Musa Yilmaz  2 , Farhad Ravandi  2
Affiliations
Review

Current status and research directions in acute myeloid leukemia

Hagop Kantarjian et al. Blood Cancer J. .

Abstract

The understanding of the molecular pathobiology of acute myeloid leukemia (AML) has spurred the identification of therapeutic targets and the development of corresponding novel targeted therapies. Since 2017, twelve agents have been approved for the treatment of AML subsets: the BCL2 inhibitor venetoclax; the CD33 antibody drug conjugate gemtuzumab ozogamicin; three FLT3 inhibitors (midostaurin, gilteritinib, quizartinib); three IDH inhibitors (ivosidenib and olutasidenib targeting IDH1 mutations; enasidenib targeting IDH2 mutations); two oral hypomethylating agents (oral poorly absorbable azacitidine; fully absorbable decitabine-cedazuridine [latter approved as an alternative to parenteral hypomethylating agents in myelodysplastic syndrome and chronic myelomonocytic leukemia but commonly used in AML]); and CPX-351 (encapsulated liposomal 5:1 molar ratio of cytarabine and daunorubicin), and glasdegib (hedgehog inhibitor). Other targeted therapies (menin inhibitors, CD123 antibody-drug conjugates) are showing promising results. To achieve optimal results in such a rare and heterogeneous entity as AML requires expertise, familiarity with this rare cancer, and the access to, and delivery of disparate therapies under rigorous supportive care conditions. In this review, we update the standard-of-care and investigational therapies and outline promising current and future research directions.

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Conflict of interest statement

HK reports research grants and honoraria from AbbVie, Amgen, Ascentage, BMS, Daiichi-Sankyo, Immunogen, Novartis; honoraria from Ipsen Biopharmaceuticals, KAHR Medical, Shenzhen Target Rx, Stemline, Takeda. TK reports grant or research support from BMS, Celgene, Pfizer, Amgen, Jazz, AstraZeneca and Genentech; consultant fees from Agios, Jazz, Genentech and Novartis. CDiN reports research support to institution from Abbvie, Agios, Bayer, Calithera, Cleave, BMS/Celgene, Daiichi-Sankyo and ImmuneOnc; consultant/advisory boards with Abbvie, Agios, Celgene/BMS, Daiichi-Sankyo, ImmuneOnc, Novartis, Takeda and Notable Labs. ND reports research funding from Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, Gilead, Sevier, Genentech, Astellas, Daiichi-Sankyo, Abbvie, Hanmi, Trovagene, FATE, Amgen, Novimmune, Glycomimetics, and ImmunoGen and has served in a consulting or advisory role for Daiichi-Sankyo, Bristol-Myers Squibb, Pfizer, Novartis, Celgene, AbbVie, Astellas, Genentech, Immunogen, Servier, Syndax, Trillium, Gilead, Amgen and Agios. GB reports research funding from Bristol‐Myers Squibb, GlaxoSmithKline, Janssen Scientific Affairs, Eli Lilly and Company, Cyclacel, AstraZeneca, AbbVie, Oncoceutics, Arvinas, Cantargia, PTC Therapeutics, Argenx, BioTheryX, and Bioline and personal fees from PTC Therapeutics, Argenx, BioTheryX, and Bioline. GI reports research funding from Celgene, Merck, Kura Oncology, Syndax, Astex and Novartis, and received consultancy or advisory board fees from NuProbe, AbbVie, Novartis, Sanofi, AstraZeneca, Syndax and Kura Oncology. EJ reports research grants and advisory rolls with AbbVie, Adaptive Biotechnologies, Amgen, BMS, Pfizer and Takeda, and advisory role with Genetech. FR reports research funding from BMS, Amgen, Xencor, Macrogenics, Orsenix, Abbvie, Prelude, Astex; consultancy and honoraria from Celgene, BMS, Amgen, Astellas, Xencor, Agios, AstraZeneca and Orsenix.

Figures

Fig. 1
Fig. 1. Survival of de novo acute myeloid leukemia at MD Anderson (1980–2023) on protocol therapies by age and treatment era.
A Age <60 years; B age 60+ years. Survival of patients on- and off-protocol therapies: C age <60 years; D age 60+ years. Reasons for off protocol vary: patient choice, socioeconomic reasons, geography, insurance.
Fig. 2
Fig. 2
Survival of acute promyelocytic leukemia at MD Anderson (1980–2023).
Fig. 3
Fig. 3. Survival of core-binding factor acute myeloid leukemia at MD Anderson with FLAG-GO versus FLAG-IDA.
A Overall; B age <60 years; C age 60+ years.
Fig. 4
Fig. 4. Therapy of AML.
A With 3+7 standard of care; B in younger AML at MD Anderson; C in older AML at MD Anderson.
See this image and copyright information in PMC

References

    1. Kantarjian H. Acute myeloid leukemia-major progress over four decades and glimpses into the future. Am J Hematol. 2016;91:131–45. - PubMed
    1. Kantarjian H, Kadia T, DiNardo C, Daver N, Borthakur G, Jabbour E, et al. Acute myeloid leukemia: current progress and future directions. Blood Cancer J. 2021;11:41. - PMC - PubMed
    1. Kantarjian HM, Kadia TM, DiNardo CD, Welch MA, Ravandi F. Acute myeloid leukemia: Treatment and research outlook for 2021 and the MD Anderson approach. Cancer 2021;127:1186–207. - PMC - PubMed
    1. Kantarjian HM, Short NJ, Fathi AT, Marcucci G, Ravandi F, Tallman M, et al. Acute myeloid leukemia: historical perspective and progress in research and therapy over 5 decades. Clin Lymphoma Myeloma Leuk. 2021;21:580–97. - PMC - PubMed
    1. Kantarjian H, Short NJ, DiNardo C, Stein EM, Daver N, Perl AE, et al. Harnessing the benefits of available targeted therapies in acute myeloid leukaemia. Lancet Haematol. 2021;8:e922–e33. - PMC - PubMed

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