FDA Approves Venetoclax Combination For Newly Diagnosed AML in Adults 75 Years or Older

The Food and Drug Administration (FDA) recently announced its approval of Venetoclax (Venclexta)  in combination with either decitabine or azacitidine (hypomethylating agents) or cytarabine (an antimetabolite) to treat adults 75 years or older, who were newly diagnosed with acute myeloid leukemia (AML).

The FDA based its approval on two trials, M14-358 and M14-387. Both trials were open-label non-randomized trials in which the investigators and patients know which drugs each patient receives. Complete remission (CR) and CR duration were some of the endpoints of the trial.

A number of AML patients also had medical conditions that prevented them from being treated with intensive induction chemotherapy.

Milder treatments such as the Ventoclax combination are better tolerated by older patients, as not only is it a matter of age but treatments are often complicated by various illnesses (comorbidities) that accompany advanced years.

These treatments have the potential of becoming the standard of care for patients who are unable to tolerate the current induction therapy.

Study M14-358 

Study M14-358 investigated venetoclax combined with the hypomethylating agents azacitidine or decitabine in patients newly diagnosed with AML.  It was a non-randomized, open-label clinical trial involving a total of 80 patients.

Twenty-five patients (37%) on the azacitidine arm reached CR with an observed time in remission of 5.5 months. CR was achieved by seven patients, (54%) on the decitabine arm with an observed time in remission of 4.7 months. Observed time begins at the onset of CR and continues to the data cut-off date or when a patient relapses.

More information on the trial (NCT02203773) is available here.

Study M14-387

Study M14-387, was also a non-randomized open-label clinical trial involving a total of 61 patients with newly-diagnosed AML as well as patients previously exposed to a hypomethylating agent that was administered to treat other disorders (antecedent hematologic disorders) such as Myelodysplastic Syndrome.

In this trial, venetoclax was combined with low dose cytarabine. The results showed that 13 patients (21%) achieved CR. The median observed time was six months.

More information on the study (NCT02287233) is available here.

The recommended dose of venetoclax is dependant upon the regimen. See prescribing information for Venclexta.

Contingent Approval

The basis for this treatment has been given accelerated approval by the FDA. Contingent approval may rely on confirmatory trials. Previously the FDA granted the following to venetoclax:

  • priority review
  • breakthrough therapy designation, and
  • orphan product designation

A description of FDA expedited programs can be found in the Guidance for Industry: Expedited Programs for Serious Conditions-Drugs and Biologics.

Note that two phase 3 studies, VIALE-A (NCT02993523) and VIALE-C (NCT03069352) to evaluate venetoclax with azacitidine or low-dose cytarabine are ongoing. The primary endpoint of these trials is overall survival. They are intended as the confirmatory trials.


Rose Duesterwald

Rose Duesterwald

Rose became acquainted with Patient Worthy after her husband was diagnosed with Acute Myeloid Leukemia four years ago. He was treated with a methylating agent While he was being treated with a hypomethylating agent, Rose researched investigational drugs being developed to treat relapsed/refractory AML.

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