Bruton Tyrosine Kinase Inhibition: an Effective Strategy to Manage Waldenstr öm Macroglobulinemia

AbstractPurpose of ReviewThe treatment of Waldenstr öm macroglobulinemia (WM) has evolved over the past decade. With the seminal discoveries ofMYD88 andCXCR warts, hypogammaglobulinemia, infections, and myelokathexis (WHIM) mutations in WM cells, our understanding of the disease biology and treatment has improved. The development of a new class of agents, Bruton tyrosine kinase inhibitors (BTKi), has substantially impacted the treatment paradigm of WM. Herein, we review the current and emerging BTKi and the evidence for their use in WM.Recent FindingsClinical trials have established the role of covalent BTKi in the treatment of WM. Their efficacy is compromised among patients who harborCXCR4WHIM mutation orMYD88WT genotype. The development of BTKC481 mutation-mediated resistance to covalent BTKi may lead to disease refractoriness. Novel, non-covalent, next-generation BTKi are emerging, and preliminary results of the early phase clinical trials show promising activity in WM, even among patients refractory to a covalent BTKi.SummaryCovalent BTK inhibitors have demonstrated meaningful outcomes in treatment-na ïve (TN) and relapsed refractory (R/R) WM, particularly among those harboring theMYD88L265P mutation. The next-generation BTKi demonstrate improved selectivity, resulting in a more favorable toxicity profile. In WM, BTKi are administered until progression or the development of intolerable toxicity. Consequently, the potential for acquired resistance, the emergence of cumu...
Source: Current Hematologic Malignancy Reports - Category: Hematology Source Type: research