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
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Adenine / adverse effects
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Adenine / analogs & derivatives
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Adenine / therapeutic use
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Agammaglobulinaemia Tyrosine Kinase / antagonists & inhibitors*
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Antineoplastic Agents / adverse effects
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Antineoplastic Agents / pharmacokinetics
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Antineoplastic Agents / therapeutic use*
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Atrial Fibrillation / chemically induced
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Benzamides / therapeutic use
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Central Nervous System Diseases / drug therapy
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Central Nervous System Diseases / etiology
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Clinical Trials as Topic
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Febrile Neutropenia / chemically induced
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Gastrointestinal Diseases / chemically induced
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Multicenter Studies as Topic
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Myeloid Differentiation Factor 88 / antagonists & inhibitors
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Myeloid Differentiation Factor 88 / genetics
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NF-kappa B / metabolism
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Neoplasm Proteins / antagonists & inhibitors*
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Neoplasm Proteins / genetics
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Piperidines / adverse effects
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Piperidines / pharmacokinetics
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Piperidines / therapeutic use*
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Progression-Free Survival
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Protein Kinase Inhibitors / adverse effects
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Protein Kinase Inhibitors / pharmacokinetics
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Protein Kinase Inhibitors / therapeutic use*
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Pyrazines / therapeutic use
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Pyrazoles / adverse effects
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Pyrazoles / pharmacokinetics
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Pyrazoles / therapeutic use*
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Pyrimidines / adverse effects
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Pyrimidines / pharmacokinetics
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Pyrimidines / therapeutic use*
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Quality of Life
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Receptors, CXCR4 / antagonists & inhibitors
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Receptors, CXCR4 / genetics
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Recurrence
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Salvage Therapy
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Signal Transduction / drug effects
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Treatment Outcome
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Waldenstrom Macroglobulinemia / complications
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Waldenstrom Macroglobulinemia / drug therapy*
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Waldenstrom Macroglobulinemia / enzymology
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Waldenstrom Macroglobulinemia / genetics
Substances
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Antineoplastic Agents
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Benzamides
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CXCR4 protein, human
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MYD88 protein, human
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Myeloid Differentiation Factor 88
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NF-kappa B
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Neoplasm Proteins
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Piperidines
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Protein Kinase Inhibitors
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Pyrazines
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Pyrazoles
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Pyrimidines
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Receptors, CXCR4
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ibrutinib
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zanubrutinib
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Agammaglobulinaemia Tyrosine Kinase
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BTK protein, human
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acalabrutinib
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Adenine