Zanubrutinib for the treatment of Waldenström Macroglobulinemia

Expert Rev Hematol. 2020 Dec;13(12):1303-1310. doi: 10.1080/17474086.2020.1851184. Epub 2020 Dec 9.

Abstract

Introduction: Waldenström Macroglobulinaemia (WM) is a heterogeneous, incurable condition which often relapses after chemoimmunotherapy. Novel therapies such as Bruton tyrosine-kinase (BTK) inhibitors have shown to be efficacious in treating WM but with an established, significant toxicity profile seen in the first-generation inhibitor Ibrutinib. Zanubrutinib is a selective, potent BTK inhibitor with the potential to reduce toxicity and improve efficacy. Areas covered: This review examines the activity of Zanubrutinib in treating treatment-naïve and relapsed refractory WM and it's toxicity profile when compared to Ibrutinib. Outcomes from the AU003 and ASPEN studies will be examined in detail including a particular focus on MYD88WT and CXCR4WHIM disease. Strengths and weaknesses of this treatment approach will be highlighted and future directions for research will be identified. Expert opinion: Zanubrutinib induces deeper responses and have greater activity in MYD88WT and CXCR4WHIM WM. Zanubrutinib also has a favorable toxicity profile when compared to Ibrutinib. This may potentially translate to lower discontinuation rates, improved quality of life and ultimately longer progression-free survival in patients with WM.

Keywords: BTK inhibitor; Ibrutinib; Waldenström Macroglobulinaemia; Zanubrutinib; lymphoma.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adenine / adverse effects
  • Adenine / analogs & derivatives
  • Adenine / therapeutic use
  • Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use*
  • Atrial Fibrillation / chemically induced
  • Benzamides / therapeutic use
  • Central Nervous System Diseases / drug therapy
  • Central Nervous System Diseases / etiology
  • Clinical Trials as Topic
  • Febrile Neutropenia / chemically induced
  • Gastrointestinal Diseases / chemically induced
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Multicenter Studies as Topic
  • Myeloid Differentiation Factor 88 / antagonists & inhibitors
  • Myeloid Differentiation Factor 88 / genetics
  • NF-kappa B / metabolism
  • Neoplasm Proteins / antagonists & inhibitors*
  • Neoplasm Proteins / genetics
  • Piperidines / adverse effects
  • Piperidines / pharmacokinetics
  • Piperidines / therapeutic use*
  • Progression-Free Survival
  • Protein Kinase Inhibitors / adverse effects
  • Protein Kinase Inhibitors / pharmacokinetics
  • Protein Kinase Inhibitors / therapeutic use*
  • Pyrazines / therapeutic use
  • Pyrazoles / adverse effects
  • Pyrazoles / pharmacokinetics
  • Pyrazoles / therapeutic use*
  • Pyrimidines / adverse effects
  • Pyrimidines / pharmacokinetics
  • Pyrimidines / therapeutic use*
  • Quality of Life
  • Receptors, CXCR4 / antagonists & inhibitors
  • Receptors, CXCR4 / genetics
  • Recurrence
  • Salvage Therapy
  • Signal Transduction / drug effects
  • Treatment Outcome
  • Waldenstrom Macroglobulinemia / complications
  • Waldenstrom Macroglobulinemia / drug therapy*
  • Waldenstrom Macroglobulinemia / enzymology
  • Waldenstrom Macroglobulinemia / genetics

Substances

  • Antineoplastic Agents
  • Benzamides
  • CXCR4 protein, human
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • Neoplasm Proteins
  • Piperidines
  • Protein Kinase Inhibitors
  • Pyrazines
  • Pyrazoles
  • Pyrimidines
  • Receptors, CXCR4
  • ibrutinib
  • zanubrutinib
  • Agammaglobulinaemia Tyrosine Kinase
  • BTK protein, human
  • acalabrutinib
  • Adenine