ALPINE: zanubrutinib versus ibrutinib in relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma

Future Oncol. 2020 Apr;16(10):517-523. doi: 10.2217/fon-2019-0844. Epub 2020 Mar 24.


Treatment standards for chronic lymphocytic leukemia (CLL) have been transformed with the advent of effective inhibitors of B-cell receptor signaling such as ibrutinib - a first-in-class inhibitor of BTK. Off-target kinase inhibitions by ibrutinib are thought to contribute to its adverse events. Zanubrutinib is a next-generation BTK inhibitor with minimal off-target effects, sustained BTK occupancy in peripheral blood mononuclear cells and lymph nodes from patients with B-cell malignancies and promising responses in patients with CLL. Described here is a head-to-head Phase III study comparing the efficacy and safety of zanubrutinib with those of ibrutinib in patients with CLL/small lymphocytic lymphoma in the relapsed/refractory setting.

Keywords: BTK inhibitor; Bruton tyrosine kinase; chronic lymphocytic leukemia; clinical trials; comparative effectiveness; hematologic/leukemia; ibrutinib; zanubrutinib.

Publication types

  • Clinical Trial Protocol

MeSH terms

  • Adenine / analogs & derivatives
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors
  • Agammaglobulinaemia Tyrosine Kinase / metabolism
  • Chronic Disease
  • Clinical Trials, Phase III as Topic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell / drug therapy*
  • Leukemia, Lymphocytic, Chronic, B-Cell / pathology
  • Outcome Assessment, Health Care
  • Piperidines / adverse effects
  • Piperidines / therapeutic use*
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazoles / adverse effects
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Safety


  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazoles
  • Pyrimidines
  • ibrutinib
  • zanubrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • Adenine