title: Ibrutinib for the treatment of Waldenström macroglobulinemia.
abstract: Waldenström macroglobulinemia (WM) is a B-cell non-Hodgkin lymphoma (NHL) characterized by IgM monoclonal gammopathy and bone marrow infiltration by lymphoplasmacytic cells. Until recently, there was no drug specifically approved for WM by the US FDA, leading to wide variations in therapeutic strategies across the globe. Ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, is the first drug approved specifically for WM by the FDA after a clinical trial showed impressive response in previously treated WM. Ibrutinib is a non-stem cell toxic and non-neurotoxic option and suitable for long-term oral maintenance therapy, with the potential of improving survival in WM. With identification of novel genetic mutations impacting response to ibrutinib, it would be possible to individualize therapy based on MYD88 and CXCR4 genotypes. However, long-term safety and efficacy data are required, and cost-effectiveness needs to be addressed before ibrutinib can gain widespread acceptance for front-line therapy of WM.
authors.affiliation: a Mayo Clinic, Rochester, MN, USA.
authors.forename: Rajshekhar
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Prashant
authors.initials: P
authors.lastname: Kapoor
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Ansell
authors.forename: Morie A
authors.initials: MA
authors.lastname: Gertz
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017277:Drug Approval; D016527:Drug Costs; D004353:Drug Evaluation, Preclinical; D019008:Drug Resistance, Neoplasm; D006801:Humans; D010880:Piperidines; D047428:Protein Kinase Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D011743:Pyrimidines / Q000494:pharmacology / Q000627:therapeutic use*; D016896:Treatment Outcome; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality
chemical_list: D000970:Antineoplastic Agents; D010880:Piperidines; D047428:Protein Kinase Inhibitors; D011720:Pyrazoles; D011743:Pyrimidines; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; D000225:Adenine
keywords: Waldenström macroglobulinemia; bruton tyrosine kinase; ibrutinib; immunoglobin M; lymphoplasmacytic lymphoma