Efficacy and Biological Correlates of Response in a Phase 2 Study of Venetoclax Monotherapy in Patients with Acute Myelogenous Leukemia

By M. Konopleva, D. Pollyea, J. Potluri, B. Chyla, L. Hogdal, T. Busman, E. Mckeegan, A. Salem, Ming Zhu, J. Ricker and 12 more. Cancer Discovery, 2016

900 citations recorded by the source corpus.

We present a phase 2, single-arm study evaluating 800 mg daily venetoclax, a highly selective, oral small-molecule B-cell leukemia/lymphoma-2 (BCL-2) inhibitor in patients with high-risk relapsed/refractory acute myelogenous leukemia (AML) or unfit for intensive chemotherapy. Responses were evaluated following revised International Working Group (IWG) criteria. The overall response rate was 19%; an additional 19% of patients demonstrated anti-leukemic activity not meeting IWG criteria (partial bone marrow response and incomplete hematologic recovery). Twelve (38%) patients had isocitrate dehydrogenase 1/2 mutations, of whom 4 (33%) achieved complete response/complete response with incomplete blood count recovery. Six (19%) patients had BCL-2–sensitive protein index at screening, which correlated with time on study. BH3 profiling was consistent with on-target BCL-2 inhibition and identified potential resistance mechanisms. Common adverse events included nausea, diarrhea and vomiting (all grades), and febrile neutropenia and hypokalemia (grade 3/4). Venetoclax demonstrated activity and acceptable tolerability in patients with AML and adverse features.

Subfields: Hematology, Public Health, Environmental and Occupational Health

View Paper: https://www.semanticscholar.org/paper/245982f9a9ee6f942d28c1395326fb4ae9ab0a46

How researchers see this paper

The researchers whose trusted networks rank it highest, strongest advocate first. Every researcher gets a different order.

  1. Pengfei Shi
  2. H. Cui
  3. Zhen Dong
  4. Fei Chen
  5. Gaichao Zhao
  6. Jiayi Zhang
  7. Wen Peng
  8. Guanghui Zhang

Citations in the corpus