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Clinical trial summary: Venetoclax plus LDAC for adult AML patients at high risk of toxicity

Clinical challenge

Acute myeloid leukemia (AML) patients ages 75 and older, and younger adults with comorbidities, are often ineligible to receive standard intensive chemotherapy due to high rates of toxicity and early mortality. As a result, supportive care is all that’s available to about 60% of adults 75 or older and younger adults with comorbidities.

Clinical trial

The trial was conducted as a randomized, double-blind, placebo-controlled, multicenter phase 3 study. It evaluated the efficacy and safety of venetoclax plus low-dose cytarabine (LDAC) combination therapy compared with placebo plus LDAC in patients with AML who had not received prior treatment for AML and were ineligible for intensive chemotherapy.

The primary objective of the study was to assess whether venetoclax led to an improvement in overall survival compared with the placebo plus LDAC.

Treatment: Patients were randomized to receive either venetoclax or placebo. Patients received 100 milligrams venetoclax orally on day 1, 200 milligrams on day 2, 400 milligrams  on day 3, and 600 milligrams daily on days 4 through 28 of cycle 1 and daily in all subsequent 28-day cycles. Patients randomized to the placebo were administered placebo in the same manner as venetoclax. All patients received LDAC (20 mg/m2 subcutaneously) on days 1 through 10 of each 28-day cycle.

Results

Median overall survival was longer in patients on venetoclax (8.4 months) compared with those on placebo (4.1 months). The risk of death was reduced by 30% in patients on venetoclax compared with those on placebo.

Conclusions

This six-month follow-up analysis demonstrates that in addition to its manageable safety profile, venetoclax improves key efficacy measures including overall survival, complete response rates, transfusion independence and event-free survival compared with LDAC alone. The results confirm its promise in this subset of older patients with AML who serve to benefit from an effective, less intensive therapeutic option.

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To refer a patient to Norton Cancer Institute, visit Norton EpicLink and choose EpicLink referral to Hematology / Oncology.

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