SAN DIEGO Venetoclax in combination with low-dose cytarabine appears active, with a tolerable safety profile, in older, treatment-naive patients with acute myeloid leukemia (AML) who are unfit for intensive chemotherapy, according to a study presented at the American Society of Hematology (ASH) 58th Annual Meeting and Exposition.1

“Older patients with AML who are often unfit for intensive chemotherapy have limited treatment options,” said Andrew Wei, of the Australian Centre for Blood Diseases, Alfred Hospital, and Monash University in Australia. “Targeting the pro-survival molecule, BCL-2, has demonstrated clinical efficacy as a therapeutic strategy in various hematologic malignancies.”

For this phase 1/2 study ( Identifier: NCT02287233), researchers evaluated the safety and efficacy of venetoclax, a BCL-2 inhibitor, plus low-dose cytarabine in older patients with newly-diagnosed AML unfit for intensive therapy.

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The researchers enrolled 20 patients aged 65 years or older who had not received prior therapy for AML and were ineligible to undergo intensive chemotherapy. In phase 1, 18 patients received venetoclax 600 or 800 mg orally once daily plus low-dose cytarabine subcutaneously in 28-day cycles, and in phase 2, 53 patients received venetoclax 600 mg with low-dose cytarabine.

The study showed that 61% of patients treated with venetoclax 600 mg achieved an overall response, including 21% with complete remissions and 33% with complete remission with incomplete marrow recovery. Seventy percent achieved a complete remission or complete remission with incomplete marrow recovery during cycles 1 and 2.

Median overall survival has not yet been reached, though the overall response rate is highly correlated with overall survival.

“Clinical activity and tolerability were seen in patients age 75 years or older, or with secondary AML, adverse karyotype, FLT3-ITD mutations, and IDH 1/2 mutations,” said Dr Wei.

The most common treatment-emergent adverse events were nausea, hypokalemia, diarrhea, fatigue, decreased appetite, constipation, febrile neutropenia, and vomiting. The most frequently reported grade 3 to 4 adverse events were febrile neutropenia, hypokalemia, hypophosphatemia, and hypertension.

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“Venetoclax plus low-dose cytarabine demonstrates significant and durable activity in elderly patients with treatment-naive AML ineligible to receive intensive induction chemotherapy,” Dr Wei concluded. “A future randomized trial is planned to evaluate this combination by AbbVie.”


  1. Wei A, Strickland SA, Roboz GJ, et al. Safety and efficacy of venetoclax plus low-dose cytarabine in treatment-naive patients aged ≥65 years with acute myeloid leukemia. Paper presented at: American Society of Hematology (ASH) 58th Annual Meeting and Exposition; December 3-6, 2016; San Diego, CA.