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Treatment of Relapsed/Refractory Acute Myeloid Leukemia

  • Leukemia (PH Wiernik, Section Editor)
  • Published:
Current Treatment Options in Oncology Aims and scope Submit manuscript

Opinion statement

Approximately 40–45% of younger and 10–20% of older adults with acute myeloid leukemia (AML) will be cured with current standard chemotherapy. The outlook is particularly gloomy for patients with relapsed and/or refractory disease (cure rates no higher than 10%). Allogeneic hematopoietic stem cell transplantation (HSCT), the only realistic hope of cure for these patients, is an option for only a minority. In recent years, much has been learned about the genomic and epigenomic landscapes of AML, and the clonal architecture of both de novo and secondary AML has begun to be unraveled. These advances have paved the way for rational drug development as new “drugable” targets have emerged. Although no new drug has been approved for AML in over four decades, with the exception of gemtuzumab ozogamycin, which was subsequently withdrawn, there is progress on the horizon with the possible regulatory approval soon of agents such as CPX-351 and midostaurin, the Food and Drug Administration “breakthrough” designation granted to venetoclax, and promising agents such as the IDH inhibitors AG-221 and AG-120, the smoothened inhibitor glasdegib and the histone deacetylase inhibitor pracinostat. In our practice, we treat most patients with relapsed/refractory AML on clinical trials, taking into consideration their prior treatment history and response to the same. We utilize targeted sequencing of genes frequently mutated in AML to identify “actionable” mutations, e.g., in FLT3 or IDH1/2, and incorporate small-molecule inhibitors of these oncogenic kinases into our therapeutic regimens whenever possible. In the absence of actionable mutations, we rationally combine conventional agents with other novel therapies such as monoclonal antibodies and other targeted drugs. For fit patients up to the age of 65, we often use high-dose cytarabine-containing backbone regimens. For older or unfit patients, we prefer hypomethylating agent-based therapy. Finally, all patients with relapsed/refractory AML are evaluated for allogeneic HSCT.

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Acknowledgements

This work was supported in part by the MD Anderson Cancer Center Support Grant No. P30 CA016672 from the National Institutes of Health.

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Authors and Affiliations

  1. Department of Leukemia, University of Texas MD Anderson Cancer Center, 1400 Holcombe Blvd, FC4.3062, Houston, TX, 77030, USA

    Prithviraj Bose MD & Jorge E. Cortes MD

  2. Department of Medicine, Roswell Park Cancer Institute, Buffalo, NY, USA

    Pankit Vachhani MD

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  1. Prithviraj Bose MD
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  2. Pankit Vachhani MD
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  3. Jorge E. Cortes MD
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Correspondence to Jorge E. Cortes MD.

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Conflict of Interest

Prithviraj Bose has received research funding through a grant from Celgene Corporation.

Pankit Vachhani declares that he has no conflict of interest.

Jorge E. Cortes has received research funding through grants from Arog, Celator, Pfizer, Novartis, Tolero, Janssen, FORMA Therapeutics, Daiichi, Astellas, and Bristol-Myers Squibb; and has received compensation from Celator, Pfizer, Novartis, Janssen, Aegios, Astellas, and Bristol-Myers Squibb for service as a consultant.

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Bose, P., Vachhani, P. & Cortes, J.E. Treatment of Relapsed/Refractory Acute Myeloid Leukemia. Curr. Treat. Options in Oncol. 18, 17 (2017). https://doi.org/10.1007/s11864-017-0456-2

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