Secondary AML Emerging After Therapy with Hypomethylating Agents: Outcomes, Prognostic Factors, and Treatment Options

Abstract

Purpose of Review

Secondary AML (s-AML) encompasses a distinct subgroup of AML with either therapy-related AML or AML arising from preexisting myeloid neoplasms. Despite recent advances in the treatment armamentarium of AML, outcomes remain poor in s-AML. The purpose of this review is to highlight distinct characteristics, prognostic factors, and treatment options for patients with s-AML. Further, we focus on a distinctly poor-risk subgroup of s-AML with previous exposure to hypomethylating agents (HMAs) and describe ongoing clinical trials in this patient population.

Recent Findings

CPX-351 (liposomal daunorubicin and cytarabine) is the first drug approved for s-AML and represents an advancement in the management of fit patients with this subtype of AML. Despite incremental improvement in remission rates and survival, long-term survival remains poor. Patients who have received prior HMAs for antecedent MDS rarely benefit from CPX-351 or other cytotoxic chemotherapy regimens. The approval of venetoclax in combination with azacitidine has led to a paradigm shift in the management of newly diagnosed older unfit AML patients; however, patients with s-AML and prior HMA therapy were excluded from the landmark randomized phase 3 study. Several early phase clinical trials with both low- and high-intensity therapies are ongoing for s-AML patients, though prior HMA exposure limits inclusion in many of these studies that include HMAs.

Summary

Patients with s-AML previously treated with an HMA have dismal outcomes with standard therapeutic options and are under-represented in clinical trials. Trials investigating novel therapeutic options in this population are critically needed.

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Correspondence to Joshua F. Zeidner.

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MCF has served as a consultant for Daiichi-Sankyo and Macrogenics and has received institutional research funding from Bellicum Pharmaceuticals and Macrogenics.

JFZ has received honoraria from Agios, Bristol-Myers Squibb/Celgene, Daiichi-Sankyo, Genentech, Pfizer, and Takeda; has served as a consultant for AbbVie, AsystBio Laboratories, Celgene, and Takeda; and has received institutional research funding from AROG, Forty Seven, Merck, Sumitomo Dainippon Pharma, and Takeda.

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Richardson, D.R., Green, S.D., Foster, M.C. et al. Secondary AML Emerging After Therapy with Hypomethylating Agents: Outcomes, Prognostic Factors, and Treatment Options. Curr Hematol Malig Rep (2021). https://doi.org/10.1007/s11899-021-00608-6

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Keywords

  • Acute myeloid leukemia
  • Secondary AML
  • Hypomethylating agents
  • Venetoclax
  • CPX-351
  • Clinical trials