Evaluating zanubrutinib for the treatment of adults with chronic lymphocytic leukemia or small lymphocytic lymphoma

Expert Rev Hematol. 2024 Jun;17(6):201-210. doi: 10.1080/17474086.2024.2356257. Epub 2024 May 24.

Abstract

Introduction: This review evaluates zanubrutinib as a treatment option for adults with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL). Zanubrutinib, a covalent BTK (Bruton's tyrosine kinase) inhibitor, was recently approved by the US FDA based in part on head-to-head data demonstrating improved efficacy and safety compared to ibrutinib.

Areas covered: The review discusses the efficacy, safety, and comparative advantages of zanubrutinib, highlighting its safety profile compared to other BTK inhibitors. It also addresses the unmet needs of current therapies in CLL/SLL and provides an overview of competitor compounds and ongoing research in BTK inhibition.

Expert opinion: Zanubrutinib, the first BTK inhibitor to demonstrate superior efficacy and safety compared to another BTK inhibitor in CLL, is likely to be widely adopted due to its high-quality data and ease of use. Looking ahead, pirtobrutinib, a novel non-covalent BTK inhibitor, has shown promise in heavily pretreated CLL patients, including those unresponsive to covalent inhibitors, with ongoing phase 3 trials comparing it against ibrutinib. The field is also exploring time-limited therapies like the combination of ibrutinib and venetoclax, with ongoing trials evaluating different combinations to optimize efficacy and minimize toxicity, indicating a promising future for combination therapies in CLL treatment.

Keywords: BTK inhibitors; Chronic lymphocytic leukemia (CLL); hematologic malignancy; lymphoma; novel therapies; small lymphocytic lymphoma (SLL); zanubrutinib.

Publication types

  • Review

MeSH terms

  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Adult
  • Agammaglobulinaemia Tyrosine Kinase* / antagonists & inhibitors
  • Antineoplastic Agents / therapeutic use
  • Clinical Trials as Topic
  • Humans
  • Leukemia, Lymphocytic, Chronic, B-Cell* / drug therapy
  • Piperidines* / therapeutic use
  • Protein Kinase Inhibitors* / adverse effects
  • Protein Kinase Inhibitors* / therapeutic use
  • Pyrazoles* / therapeutic use
  • Pyrimidines* / therapeutic use
  • Sulfonamides / therapeutic use
  • Treatment Outcome

Substances

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