Venetoclax Approved for Older Patients With AML

NOVEMBER 21, 2018
Rare Disease Editorial Staff
The US Food and Drug Administration (FDA) has granted accelerated approval of Venetoclax (Venclexta, Abbvie | Genentech) combined use with azacytidine, or decitabine, or low-dose cytarabine as a treatment for adult patients with newly-diagnosed acute myeloid leukemia (AML) who are 75 years or older, or who have comorbidities that preclude the use of intensive induction chemotherapy.

The approval is based on findings from the M14-358 study and the M14-387 study, 2 phase 1b/2 trials. The results from the M14-358 trial showed combining venetoclax with azacitidine led to a complete remission (CR) rate of 37% and a CR with partial hematological recovery (CRh) rate of 24%, compared with 54% and 7.7%, respectively, with the combination of venetoclax and decitabine.

The M14-387 trial examined venetoclax in combination with low-dose cytarabine and 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 1b open-label dose escalation and expansion M14-358 study (NCT02203773) included treatment-naïve patients with AML who were 60 years or older and 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 1b/2 dose escalation and expansion M14-387 study (NCT02287233) included previously untreated patients 60 years or older 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.

Venetoclax’s accelerated approval for AML is contingent on the results of a confirmatory trial.

An earlier version of this article was published as, “Frontline Venetoclax Granted Accelerated FDA Approval for Older Patients With AML,” on Targeted

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