Real-world effectiveness of first-line azacitidine or decitabine with or without venetoclax in acute myeloid leukemia patients unfit for intensive therapy

Eur J Haematol. 2024 Nov;113(5):623-630. doi: 10.1111/ejh.14278. Epub 2024 Jul 18.

Abstract

Background: First-line treatment in patients with acute myeloid leukemia (AML) unfit for intensive therapy is the combination of a hypomethylating agent (HMA) with venetoclax (VEN). However, retrospective data confirming the benefits of this regimen outside of clinical trials have shown conflicting results.

Methods: We performed a multicenter retrospective analysis of outcomes with first-line HMA-VEN versus HMA in AML patients unfit for intensive chemotherapy.

Results: A total of 213 patients were included from three German hospitals (125 HMA-VEN, 88 HMA). Median overall survival in the HMA-VEN cohort was 7.9 months (95% confidence interval [CI], 5.1-14.7) versus 4.9 months (3.1-7.1) with HMA. After 1 year, 42% (95% CI, 33-54) and 19% (12-30) of patients were alive, respectively (hazard ratio [HR] for death, 0.64; 95% CI, 0.46-0.88). After adjusting for clinical and molecular baseline characteristics, treatment with HMA-VEN remained significantly associated with both prolonged survival (HR, 0.48; 95% CI, 0.29-0.77) and time to next treatment (HR, 0.63; 95% CI, 0.47-0.85). Patients who achieved recovery of peripheral blood counts had a favorable prognosis (HR for death, 0.52; 95% CI, 0.33-0.84).

Discussion: These data align with findings from the pivotal VIALE-A trial and support the use of HMA-VEN in patients unfit for intensive therapy.

Keywords: AML; azacitidine; decitabine; hypomethylating agent; real‐world data; venetoclax.

Publication types

  • Multicenter Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antineoplastic Combined Chemotherapy Protocols* / adverse effects
  • Antineoplastic Combined Chemotherapy Protocols* / therapeutic use
  • Azacitidine* / administration & dosage
  • Azacitidine* / adverse effects
  • Azacitidine* / therapeutic use
  • Bridged Bicyclo Compounds, Heterocyclic* / administration & dosage
  • Bridged Bicyclo Compounds, Heterocyclic* / therapeutic use
  • Decitabine* / administration & dosage
  • Decitabine* / therapeutic use
  • Female
  • Humans
  • Leukemia, Myeloid, Acute* / diagnosis
  • Leukemia, Myeloid, Acute* / drug therapy
  • Leukemia, Myeloid, Acute* / mortality
  • Male
  • Middle Aged
  • Prognosis
  • Retrospective Studies
  • Sulfonamides* / administration & dosage
  • Sulfonamides* / therapeutic use
  • Treatment Outcome

Substances

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