Venetoclax in combination with hypomethylating agent for the treatment of advanced myeloproliferative neoplasms and acute myeloid leukemia with extramedullary disease

Leuk Lymphoma. 2023 Apr;64(4):846-855. doi: 10.1080/10428194.2023.2173523. Epub 2023 Feb 6.

Abstract

The combination of venetoclax and hypomethylating agent (HMA/venetoclax) has emerged as a treatment option for patients with de novo acute myeloid leukemia (AML) who are unfit to receive intensive chemotherapy. In this single-center retrospective study, we evaluated clinical outcomes following treatment with HMA/venetoclax in 35 patients with advanced myeloproliferative neoplasms, myelodysplastic syndrome/myeloproliferative neoplasm overlap syndromes or AML with extramedullary disease. The composite complete remission (CR) rate (including confirmed/presumed complete cytogenetic response, acute leukemia response-complete, CR and CR with incomplete hematologic recovery) was 42.9% with median overall survival (OS) of 9.7 months. Complex karyotype was associated with inferior median OS (3.7 versus 12.2 months; p = 0.0002) and composite CR rate (22% versus 50.0%; p = 0.2444). Although SRSF2 mutations were associated with higher composite CR rate (80.0% versus 28.0%; p = 0.0082), this was not associated with longer median OS (10.9 versus 8.0 months; p = 0.2269). Future studies should include these patient subgroups.

Keywords: Myeloproliferative neoplasm; acute myeloid leukemia; azacitidine; decitabine; extramedullary disease; hypomethylating agents; myelodysplastic/myeloproliferative neoplasm; venetoclax.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / adverse effects
  • Azacitidine / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic / adverse effects
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / genetics
  • Myeloproliferative Disorders* / diagnosis
  • Myeloproliferative Disorders* / drug therapy
  • Myeloproliferative Disorders* / genetics
  • Retrospective Studies
  • Sulfonamides

Substances

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