Skip to main content
SpringerLink
Log in

Frontline Management of Elderly Acute Myeloid Leukemia Ineligible for Intensive Treatment

  • Chapter
  • First Online:
Pathogenesis and Treatment of Leukemia

  • 442 Accesses

Abstract

With the improvement of basic science and clinical translation research, the outcome of elderly patients with AML has potentially improved. Novel therapeutic regimens not only improve survival, but also increase the quality of life. Particularly, recent trials have established treatment with venetoclax in combination with HMAs or LDAC as the new standard of care for frontline management in older and unfit patients with AML who are considered unsuitable for intensive chemotherapy. Target drugs such as FLT3-inhibtors, IDH-inhibitor, or Glasdegib also bring new hope for this population. Here, we review the current treatment of elderly AML ineligible for intensive treatment.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Shallis RM, Wang R, Davidoff A, Ma X, Zeidan AM. Epidemiology of acute myeloid leukemia: recent progress and enduring challenges. Blood Rev. 2019;36:70–87.

    Article  PubMed  Google Scholar 

  2. Juliusson G, Antunovic P, Derolf A, Lehmann S, Mollgard L, Stockelberg D, et al. Age and acute myeloid leukemia: real world data on decision to treat and outcomes from the Swedish acute leukemia registry. Blood. 2009;113(18):4179–87.

    Article  CAS  PubMed  Google Scholar 

  3. Juliusson G, Lazarevic V, Hörstedt A-S, Hagberg O, Höglund M, Group ftSALR. Acute myeloid leukemia in the real world: why population-based registries are needed. Blood. 2012;119(17):3890–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Vasu S, Kohlschmidt J, Mrózek K, Eisfeld A-K, Nicolet D, Sterling LJ, et al. Ten-year outcome of patients with acute myeloid leukemia not treated with allogeneic transplantation in first complete remission. Blood Adv. 2018;2(13):1645–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Oran B, Weisdorf DJ. Survival for older patients with acute myeloid leukemia: a population-based study. Haematologica. 2012;97(12):1916–24.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Zeidan AM, Wang R, Wang X, Shallis RM, Podoltsev NA, Bewersdorf JP, et al. Clinical outcomes of older patients with AML receiving hypomethylating agents: a large population-based study in the United States. Blood Adv. 2020;4(10):2192–201.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Zeidan AM, Podoltsev NA, Wang X, Bewersdorf JP, Shallis RM, Huntington SF, et al. Temporal patterns and predictors of receiving no active treatment among older patients with acute myeloid leukemia in the United States: a population-level analysis. Cancer. 2019;125(23):4241–51.

    Article  PubMed  Google Scholar 

  8. Arber DA, Orazi A, Hasserjian R, Thiele J, Borowitz MJ, Le Beau MM, et al. The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia. Blood. 2016;127(20):2391–405.

    Article  CAS  PubMed  Google Scholar 

  9. Kantarjian H, Ravandi F, O’Brien S, Cortes J, Faderl S, Garcia-Manero G, et al. Intensive chemotherapy does not benefit most older patients (age 70 years or older) with acute myeloid leukemia. Blood. 2010;116(22):4422–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Grimwade D, Hills RK, Moorman AV, Walker H, Chatters S, Goldstone AH, et al. Refinement of cytogenetic classification in acute myeloid leukemia: determination of prognostic significance of rare recurring chromosomal abnormalities among 5876 younger adult patients treated in the United Kingdom Medical Research Council trials. Blood. 2010;116(3):354–65.

    Article  CAS  PubMed  Google Scholar 

  11. Papaemmanuil E, Gerstung M, Bullinger L, Gaidzik VI, Paschka P, Roberts ND, et al. Genomic classification and prognosis in acute myeloid leukemia. N Engl J Med. 2016;374(23):2209–21.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Shen Y, Zhu YM, Fan X, Shi JY, Wang QR, Yan XJ, et al. Gene mutation patterns and their prognostic impact in a cohort of 1185 patients with acute myeloid leukemia. Blood. 2011;118(20):5593–603.

    Article  CAS  PubMed  Google Scholar 

  13. Dohner H, Estey E, Grimwade D, Amadori S, Appelbaum FR, Buchner T, et al. Diagnosis and management of AML in adults: 2017 ELN recommendations from an international expert panel. Blood. 2017;129(4):424–47.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Pollyea DA, Bixby D, Perl A, Bhatt VR, Altman JK, Appelbaum FR, et al. NCCN guidelines insights: acute myeloid leukemia, version 2.2021. J Natl Compr Canc Netw. 2021;19(1):16–27.

    Article  PubMed  Google Scholar 

  15. Dohner H, Weisdorf DJ, Bloomfield CD. Acute myeloid leukemia. N Engl J Med. 2015;373(12):1136–52.

    Article  PubMed  Google Scholar 

  16. Burd A, Levine RL, Ruppert AS, Mims AS, Borate U, Stein EM, et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the beat AML master trial. Nat Med. 2020;26(12):1852–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Chen EC, Garcia JS. Does patient fitness play a role in determining first-line treatment of acute myeloid leukemia? Hematology. 2020;2020(1):41–50.

    Article  PubMed  PubMed Central  Google Scholar 

  18. DiNardo CD, Pratz K, Pullarkat V, Jonas BA, Arellano M, Becker PS, et al. Venetoclax combined with decitabine or azacitidine in treatment-naive, elderly patients with acute myeloid leukemia. Blood. 2019;133(1):7–17.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. DiNardo CD, Jonas BA, Pullarkat V, Thirman MJ, Garcia JS, Wei AH, et al. Azacitidine and venetoclax in previously untreated acute myeloid leukemia. N Engl J Med. 2020;383(7):617–29.

    Article  CAS  PubMed  Google Scholar 

  20. Cortes JE, Heidel FH, Hellmann A, Fiedler W, Smith BD, Robak T, 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(2):379–89.

    Article  CAS  PubMed  Google Scholar 

  21. DiNardo CD, Maiti A, Rausch CR, Pemmaraju N, Naqvi K, Daver NG, et al. 10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: a single-centre, phase 2 trial. Lancet Haematol. 2020;7(10):e724–36.

    Article  PubMed  PubMed Central  Google Scholar 

  22. DiNardo CD, Stein AS, Stein EM, Fathi AT, Frankfurt O, Schuh AC, et al. Mutant Isocitrate dehydrogenase 1 inhibitor Ivosidenib in combination with Azacitidine for newly diagnosed acute myeloid leukemia. J Clin Oncol. 2021;39(1):57–65.

    Article  CAS  PubMed  Google Scholar 

  23. Pollyea DA, Tallman MS, de Botton S, Kantarjian HM, Collins R, Stein AS, et al. Enasidenib, an inhibitor of mutant IDH2 proteins, induces durable remissions in older patients with newly diagnosed acute myeloid leukemia. Leukemia. 2019;33(11):2575–84.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. DiNardo CD, Schuh AC, Stein EM, Fernandez PM, Wei A, De Botton S, et al. Enasidenib plus azacitidine significantly improves complete remission and overall response compared with azacitidine alone in patients with newly diagnosed acute myeloid leukemia (AML) with isocitrate dehydrogenase 2 (IDH2) mutations: interim phase II results from an ongoing, randomized study. Blood. 2019;134(Suppl_1):643.

    Article  Google Scholar 

  25. Rucker FG, Schlenk RF, Bullinger L, Kayser S, Teleanu V, Kett H, et al. TP53 alterations in acute myeloid leukemia with complex karyotype correlate with specific copy number alterations, monosomal karyotype, and dismal outcome. Blood. 2012;119(9):2114–21.

    Article  PubMed  Google Scholar 

  26. Welch JS, Petti AA, Miller CA, Fronick CC, O’Laughlin M, Fulton RS, et al. TP53 and Decitabine in acute myeloid leukemia and myelodysplastic syndromes. N Engl J Med. 2016;375(21):2023–36.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Sallman DA, AE DZ, Garcia-Manero G, Steensma DP, Roboz GJ, Sekeres MA, et al. Eprenetapopt (APR-246) and azacitidine in TP53-mutant myelodysplastic syndromes. J Clin Oncol. 2021;39(14):1584–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. Wei AH, Dohner H, Pocock C, Montesinos P, Afanasyev B, Dombret H, et al. Oral azacitidine maintenance therapy for acute myeloid leukemia in first remission. N Engl J Med. 2020;383(26):2526–37.

    Article  CAS  PubMed  Google Scholar 

Download references

Conflict of Interest Statement

The authors declare no conflicts of interests.

Author information

Authors and Affiliations

  1. Department of Hematology, Leukemia Center, The First Affiliated Hospital of Zhejiang University, College of Medicine, Key Laboratory of Hematopoietic Malignancies, Zhejiang, Hangzhou, China

    Yin-Jun Lou, Jie Jin & Hong-Hu Zhu

Authors
  1. Yin-Jun Lou
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Jie Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Hong-Hu Zhu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Hong-Hu Zhu .

Editor information

Editors and Affiliations

  1. Department of Medicine, Queen Mary Hospital, Hongkong, Hong Kong

    Harinder Gill

  2. Department of Medicine, Queen Mary Hospital, Hongkong, Hong Kong

    Yok-Lam Kwong

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd.

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Lou, YJ., Jin, J., Zhu, HH. (2023). Frontline Management of Elderly Acute Myeloid Leukemia Ineligible for Intensive Treatment. In: Gill, H., Kwong, YL. (eds) Pathogenesis and Treatment of Leukemia. Springer, Singapore. https://doi.org/10.1007/978-981-99-3810-0_7

Download citation

  • DOI: https://doi.org/10.1007/978-981-99-3810-0_7

  • Published:

  • Publisher Name: Springer, Singapore

  • Print ISBN: 978-981-99-3809-4

  • Online ISBN: 978-981-99-3810-0

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation