What is the role of venetoclax in the treatment of acute myeloid leukemia (AML)?

Updated: May 26, 2020
  • Author: Karen Seiter, MD; Chief Editor: Emmanuel C Besa, MD  more...
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Similarly, venetoclax gained accelerated approval for AML in November 2018 for treatment of newly diagnosed AML in adults aged 75 years or older, or adults who have comorbidities that preclude use of intensive induction chemotherapy. It is used in combination with azacytidine or decitabine or low-dose LDAC. Venetoclax is a selective inhibitor of the B-cell lymphoma 2 (Bcl-2) regulator protein. BCL-2 overexpression has been demonstrated in AML cells, where it mediates tumor cell survival and has been associated with resistance to chemotherapeutics.

The accelerated approval of venetoclax was based on data from the phase 1b M14-358 and phase 1-2 M14-387 dose escalation and expansion studies. In the M14-358 study, complete remission was 37% (N=25/67) in the venetoclax plus azacitidine group and 54% (N=7/13) in the venetoclax plus decitabine group. [61] In the M14-387 study, the complete remission rate was 21% (N=13/61) for patients receiving venetoclax plus low-dose cytarabine. [62]  

The FDA granted full approval for venetoclax in combination with azacitidine, decitabine, or LDAC in October 2020, based on results from the phase 3 VIALE-A (M15-656) and VIALE-C (M16-043) trials. In VIALE-A, OS for patients who were receiving venetoclax plus azacitidine versus placebo was 14.7 versus 9.6 months, respectively. In VAILE-C, venetoclax did not produce statistically significant OS improvement in patients with AML who were ineligible for intensive chemotherapy. However, the complete remission (CR) rate was higher with venetoclax plus LDAC: the median CR rate in the venetoclax arm was 27%, with a median duration of 11.1 months, compared with 7.4% and a median duration of 8.3 months in the placebo group. [63]  


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