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Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches

  • Acute Myeloid Leukemias (U Borate, Section Editor)
  • Published:
Current Hematologic Malignancy Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Acute myeloid leukemia (AML) is an aggressive malignancy of the bone marrow that has a poor prognosis with traditional cytotoxic chemotherapy, especially in elderly patients. In recent years, small molecule inhibitors targeting AML-associated IDH1, IDH2, and FLT3 mutations have been FDA approved. However, the majority of AML cases do not have a targetable mutation. A variety of novel agents targeting both previously untargetable mutations and general pathways in AML are currently being investigated. Herein, we review selected new targeted therapies currently in early-phase clinical investigation in AML.

Recent Findings

The DOT1L inhibitor pinometostat in KMT2A-rearranged AML, the menin inhibitors KO-539 and SYNDX-5613 in KMT2Ar and NPM1-mutated AML, and the mutant TP53 inhibitor APR-246 are examples of novel agents targeting specific mutations in AML. In addition, BET inhibitors, polo-like kinase inhibitors, and MDM2 inhibitors are promising new drug classes for AML which do not depend on the presence of a particular mutation.

Summary

AML remains in incurable disease for many patients but advances in genomics, epigenetics, and drug discovery have led to the development of many potential novel therapeutic agents, many of which are being investigated in ongoing clinical trials. Additional studies will be necessary to determine how best to incorporate these novel agents into routine clinical treatment of AML.

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  1. Division of Hematology, Department of Internal Medicine, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA

    Nicole R. Grieselhuber & Alice S. Mims

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  1. Nicole R. Grieselhuber
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Correspondence to Alice S. Mims.

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Dr. Nicole Grieselhuber declares that she has no conflict of interest.

Dr. Alice Mims has served on the advisory boards for Syndax Pharmaceuticals, Kura Oncology, Jazz Pharmaceuticals, and AbbVie Pharmaceuticals.

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This article is part of the Topical Collection on Acute Myeloid Leukemias

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Grieselhuber, N.R., Mims, A.S. Novel Targeted Therapeutics in Acute Myeloid Leukemia: an Embarrassment of Riches. Curr Hematol Malig Rep 16, 192–206 (2021). https://doi.org/10.1007/s11899-021-00621-9

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