The Chromoscience

Azacitidine and Venetoclax in Previously Untreated Acute Myeloid Leukemia

Benison P. Zerrudo
2–3 minutes

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By Ed Uthman

  • Older patients with acute myeloid leukemia (AML) have a poor prognosis, even after treatment with a hypomethylating agent.
  • Acute myelogenous leukemia is a cancer of the blood and bone marrow — the spongy tissue inside bones where blood cells are made.
  • A hypomethylating agent or demethylating agent is a drug that inhibits DNA methylation.
  • Azacitidine added to venetoclax had promising efficacy in a previous phase 1b study.
  • Azacitidine is a chemical analog of cytidine, a nucleoside in DNA and RNA. Azacitidine and its deoxy derivative, decitabine (also known as 5-aza-2′-deoxycytidine), are used in the treatment of myelodysplastic syndrome. Both drugs were first synthesized in Czechoslovakia as potential chemotherapeutic agents for cancer.
  • This research randomly assigned previously untreated patients with confirmed AML to azacitidine plus either venetoclax or placebo.
  • The patients were ineligible for standard induction therapy because of coexisting conditions, 75 years of age or older, or both.
  • All patients received a standard dose of azacitidine.
  • Venetoclax or matching placebo was administered orally, once daily, in 28-day cycles.
  • Venetoclax is a medication used to treat adults with chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL). Venetoclax attaches to a protein called Bcl-2. This protein is present in high amounts in CLL cancer cells, where it helps the cells survive for longer in the body and makes them resistant to cancer medicines. By attaching to Bcl-2 and blocking its actions, venetoclax causes the death of cancer cells and thereby slows down progression of the disease.
  • The primary end point was overall survival.
  • The intention-to-treat population included 431 patients.
  • 286 patients were in the azacitidine-venetoclax group and 145 patients were in the azacitidine-placebo group.
  • The median overall survival was 14.7 months in the azacitidine-venetoclax group.
  • The median overall survival was 9.6 months in the control group.
  • The incidence of complete remission and composite complete remission was higher with azacitidine-venetoclax than with the control regimen.
  • Complete remission is the disappearance of signs and symptoms, while composite complete remission is a complete remission with incomplete hematologic recovery.
  • Key adverse events included nausea of any grade, and grade 3 or higher thrombocytopenia, neutropenia, and febrile neutropenia.
  • Thrombocytopenia is a condition in which you have a low blood platelet count.
  • Neutropenia occurs when you have too few neutrophils, a type of white blood cells.
  • Infections of any grade occurred in 85% of the patients in the azacitidine-venetoclax group and 67% of those in the control group.
  • Serious adverse events occurred in 83% of the patients in the azacitidine-venetoclax and 73% of those in the control group.
  • The result shows that the overall survival was longer and the incidence of remission was higher among patients who received azacitidine plus venetoclax than among those who received azacitidine alone.
  • The incidence of febrile neutropenia was higher in the venetoclax-azacitidine group than in the control group.

Sources:

https://pubmed.ncbi.nlm.nih.gov/32786187/

https://www.mayoclinic.org/diseases-conditions/acute-myelogenous-leukemia/symptoms-causes/syc-20369109

https://en.wikipedia.org/wiki/Hypomethylating_agent

https://www.mayoclinic.org/diseases-conditions/thrombocytopenia/symptoms-causes/syc-20378293

https://www.mayoclinic.org/symptoms/neutropenia/basics/definition/sym-20050854

Cihák A (1974). “Biological effects of 5-azacytidine in eukaryotes”. Oncology. 30 (5): 405–22. doi:10.1159/000224981. PMID 4142650

“Venclexta- venetoclax kit Venclexta- venetoclax tablet, film coated”. DailyMed. 12 November 2019. Retrieved 25 April 2020.

“Venclyxto EPAR”. European Medicines Agency (EMA). Retrieved 25 April2020. This article incorporates text from this source, which is in the public domain.

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