The Food and Drug Administration (FDA) has granted an accelerated approval to venetoclax (Venclexta) for use in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of newly-diagnosed adult patients with acute myeloid leukemia (AML) who are aged 75 years or older, or who have comorbidities that preclude use of intensive induction chemotherapy.
The approval is based on 2 phase Ib/II trials in this setting, the M14-358 study and the M14-387 study. In M14-358, combining venetoclax with azacitidine led to a complete remission (CR) rate of 37% and a CR with partial hematological recovery (CRh) rate of 24%. The rates were 54% and 7.7%, respectively, with the combination of venetoclax and decitabine.
M14-387 examined venetoclax in combination with low-dose cytarabine. The CR and CRh rates with the combination were both 21%.
“Many people with acute myeloid leukemia are unable to tolerate standard intensive chemotherapy, and the Venclexta combination regimens represent important new options for these patients,” Sandra Horning, chief medical officer at Genentech, a unit of Roche, said in a statement.
The phase Ib open-label dose escalation and expansion M14-358 study (NCT02203773) included treatment-naïve patients with AML aged ≥60 years who were not fit to receive intensive chemotherapy. Patients received venetoclax in combination with a hypomethylating agent (azacitidine or decitabine). Key outcome measures for the trial included CR/CRh, OS, and safety. Grade 3/4 adverse events (AEs) occurring in ≥10% of patients included anemia, low platelet count, decreased potassium levels, low white blood cell count with fever, and low white blood cell count.
The open-label phase Ib/II dose escalation and expansion M14-387 study (NCT02287233) included previously untreated patients ≥60 years who were unfit to receive intensive chemotherapy. Patients received venetoclax in combination with low-dose cytarabine. The main study endpoints were CR/CRh, objective response rate, OS, and safety. Grade 3/4 AEs experienced by at least 10% of patients included sepsis, decreased phosphate levels, high blood pressure, decreased potassium levels, pneumonia and low white blood cell count with fever.
The accelerated approval of venetoclax in AML is contingent on the results of a confirmatory trial.
Originally published by OncLive® as “FDA Approves Frontline Venetoclax in AML”