The FDA has approved venetoclax (VenclextaÒ, AbbVie Inc. and Genentech Inc.) to be used in combination with azacitidine, decitabine, or low-dose cytarabine for the treatment of acute myeloid leukemia (AML) in elderly patients or those ineligible for intensive chemotherapy.
Approval of venetoclax was determined based on two open-label, non-randomized trials involving patients with newly diagnosed AML aged 75 years or older or with comorbidities that prevent them from receiving intensive induction chemotherapy.
For the first study, M14-358 (NCT02203773), in 67 participants with newly-diagnosed AML, azacitidine/venetoclax was associated with a complete remission rate of 37%, with a median observed remission duration of 5.5 months. In 13 participants with newly diagnosed AML, decitabine/venetoclax was associated with a complete remission rate of 54%, with a median observed remission time of 4.7 months.
Findings from the second study, M14-387 (NCT02287233), showed that in 61 patients with newly diagnosed AML, venetoclax/low-dose cytarabine was associated with complete remission in 21% of patients, with a median observed remission duration of 6 months.
The most common adverse reactions to venetoclax in combination with azacitidine, decitabine, or low-dose cytarabine include nausea, diarrhea, thrombocytopenia, constipation, neutropenia, febrile neutropenia, fatigue, vomiting, peripheral edema, pneumonia, dyspnea, hemorrhage, anemia, rash, abdominal pain, sepsis, back pain, myalgia, dizziness, cough, oropharyngeal pain, pyrexia, and hypotension.
Further trials are necessary to measure overall survival as the primary end point; however, venetoclax plus azacitdine, decitabine, or low-dose cytarabine appears to be a promising combination for AML.
According to Sandra Horning, MD, Chief Medical Officer at Genentech, "Today's approval marks a significant advance for people with acute myeloid leukemia, a highly aggressive and difficult-to-treat blood cancer. Many people with acute myeloid leukemia are unable to tolerate standard intensive chemotherapy, and the [venetoclax] combination regimens represent important new options for these patients."
For More Information
Clinicaltrials.gov (2018a). Study of ABT-199 (GDC-0199) in combination with azacitidine or decitabine (chemo combo) in subjects with acute myelogenous leukemia (AML). NLM identifier: NCT02203773.
Clinicaltrials.gov (2018b). A study evaluating venetoclax in combination with low-dose cytarabine in treatment-naive subjects with acute myelogenous leukemia (AML). NLM identifier: NCT02287233.