ORLANDO ­– Combination therapy of venetoclax with decitabine or azacitidine demonstrated a tolerable safety profile and induced rapid responses with no reported relapses in elderly treatment-naïve patients with acute myeloid leukemia (AML) in an open-label, phase 1b dose-escalation trial.1

“Pro-survival BCL-2 protein is a compelling target for AML therapy,” lead investigator Courtney DiNardo, MD, assistant professor at The University of Texas MD Anderson Cancer Center in Houston, TX, said during her presentation at the American Society of Hematology’s 57th annual meeting. “BCL-2 overexpression has been implicated in the maintenance and survival of AML cells, and is associated with resistance to chemotherapy and poor survival in patients with AML.”

In this ongoing trial, researchers sought to evaluate venetoclax, a selective, potent, orally bioavailable BCL-2 inhibitor, in combination with decitabine or 5-azacitidine in treatment-naïve patients aged 65 years or older with AML. 

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Patients were included if they were not eligible for standard induction therapy and had a performance score of 2 or lower.

Participants were assigned to receive standard decitabine 20 mg/m2 intravenously daily on days 1 to 5 or 5-azacitidine 75 mg/m2 subcutaneously or intravenously daily on days 1 to 7 of each 28-day cycle for a minimum of 4 cycles in combination with once-daily continuous oral venetoclax on days 2 to 28 in cycle 1, and on days 1 to 28 for subsequent cycles.

“All patients were hospitalized for treatment and received tumor lysis prophylaxis,” Dr DiNardo noted.

Results showed that in the decitabine arm, 2 patients achieved complete remission and 1 achieved complete remission with incomplete marrow recovery with venetoclax 400 mg, while 2 patients achieved complete remission, 6 patients achieved complete remission with incomplete marrow recovery, and 2 had a partial remission with venetoclax 800 mg.

In the azacitidine treatment arm, there were 3 complete remissions with venetoclax 400 mg and 5 complete remissions with 800 mg. There was also 1 complete remission with incomplete marrow recovery in the 400-mg group and 4 in the 800-mg arm.

In regard to safety, the most common grade 4 treatment-emergent adverse events were thrombocytopenia, neutropenia, and lymphopenia. The most serious adverse event was febrile neutropenia, which occurred in 33% in the decitabine arm and in 30% of those in the azacitidine arm. “Notably, there were no events of tumor lysis syndrome,” Dr DiNardo said. “Thirteen patients had delay of cycle 2 treatment to allow for recovery of neutropenia.”

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In addition, the maximum tolerated dose of venetoclax in this patient population has not yet been determined with either treatment arm and dose escalation is still ongoing.

“The study will proceed to expansion stage as the preliminary data are encouraging,” Dr DiNardo concluded. “Neutropenia requiring dose delays with an alternative schedule of venetoclax.”


  1. DiNardo C, Pollyea D, Pratz K, et al. A phase 1b study of venetoclax (ABT-199/GDC-0199) in combination with decitabine or azacitidine in treatment-naive patients with acute myelogenous leukemia who are ≥ to 65 years and not eligible for standard induction therapy. Oral presentation at: 57th American Society of Hematology (ASH) Annual Meeting & Exposition; December 5-8, 2015; Orlando, FL.