Venetoclax combination therapy in acute myeloid leukemia and myelodysplastic syndromes

Curr Opin Hematol. 2022 Mar 1;29(2):63-73. doi: 10.1097/MOH.0000000000000698.

Abstract

Purpose of review: Venetoclax is a BCL-2 inhibitor that was approved in combination therapy with hypomethylating agents or low dose cytarabine for newly diagnosed acute myeloid leukemia (AML). The purpose of this review is to outline the most recent venetoclax-based combination therapies in newly diagnosed or relapsed myelodysplastic syndrome (MDS) and AML patients.

Recent finding: Venetoclax has been incorporated in various therapeutic regimens - either with chemotherapy, immunotherapy or targeted therapies. These combinations achieve high remission rates with deep molecular responses, as suggested by measurable residual disease measurements. There are concerns regarding the incomplete count recovery, prolonged cytopenia and infection rates, especially when combined with chemotherapy. There is also limited data concerning durability of these remissions, and the effectiveness in high-risk population (i.e. p53-mutated AML patients).

Summary: Venetoclax-based combination therapies encompass novel therapeutic possibilities in MDS and AML with encouraging initial results. However, the exact role of each combination therapy and the long-term effects on patients' outcome are yet to be defined.

Publication types

  • Review

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Bridged Bicyclo Compounds, Heterocyclic / therapeutic use
  • Cytarabine
  • Humans
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / etiology
  • Myelodysplastic Syndromes* / drug therapy
  • Myelodysplastic Syndromes* / etiology
  • Sulfonamides

Substances

  • Bridged Bicyclo Compounds, Heterocyclic
  • Sulfonamides
  • Cytarabine
  • venetoclax