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FDA Approves Venetoclax Combination for Adults With AML

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On November 21, 2018, the U.S. Food and Drug Administration (FDA) granted accelerated approval to venetoclax (Venclexta) in combination with azacitidine or decitabine or low-dose cytarabine for the treatment of newly diagnosed acute myeloid leukemia (AML) in adults who are age 75 years or older or who have comorbidities that preclude use of intensive induction chemotherapy.

Approval was based on two open-label, nonrandomized trials in patients with newly diagnosed AML who were ≥ 75 years of age or had comorbidities that precluded the use of intensive induction chemotherapy. Efficacy was established based on the rate of complete remission (CR) and CR duration.  

Trials Leading to Approval

Study M14-358 was a nonrandomized, open-label clinical trial of venetoclax in combination with azacitidine (n = 67) or decitabine (n = 13) in newly diagnosed patients with AML. In combination with azacitidine, 25 patients achieved a CR (37%, 95% confidence interval [CI] = 26–50) with a median observed time in remission of 5.5 months (range: 0.4–30 months).  In combination with decitabine, 7 patients achieved a CR (54%, 95% CI = 25–81) with a median observed time in remission of 4.7 months (range: 1.0–18 months). The observed time in remission is the time from start of CR to data cut-off date or relapse from CR.  

Study M14-387 was a nonrandomized, open-label trial of venetoclax in combination with low-dose cytarabine (n = 61) in newly diagnosed patients with AML, including patients with previous exposure to a hypomethylating agent for an antecedent hematologic disorder. In combination with low-dose cytarabine, 13 patients achieved a CR (21%, 95% CI = 12–34) with a median observed time in remission of 6 months (range: 0.03–25 months).

The most common adverse reactions (≥ 30%) to venetoclax in combination with azacitidine or decitabine or low-dose cytarabine were 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.

The recommended venetoclax dose depends upon the combination regimen and is described in the prescribing information.

This indication is approved under accelerated approval, and continued approval for this indication may be contingent upon verification and description of clinical benefit in confirmatory trials. FDA granted this application Priority Review, Breakthrough Therapy designation, and Orphan Product designation.

Two ongoing phase III studies—VIALE-A and VIALE-C—evaluating venetoclax in combination with azacitidine or low-dose cytarabine with overall survival as the primary endpoint and are intended as the confirmatory trials.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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