Novel Approaches in Waldenström Macroglobulinemia

Hematol Oncol Clin North Am. 2018 Oct;32(5):875-890. doi: 10.1016/j.hoc.2018.05.014. Epub 2018 Jul 19.

Abstract

Recent advances in the understanding of Waldenström macroglobulinemia (WM) biology have paved the way for development of a plethora of novel therapeutic strategies. The success of ibrutinib in WM has shifted treatment paradigms away from conventional chemoimmunotherapy approaches. Recognition of high-risk genomic subgroups as well as mechanisms of acquired resistance to ibrutinib have led to targeting of additional pathways. In this article, the authors review ongoing and emerging trials of novel therapies in WM that target the B-cell receptor pathway beyond ibrutinib, toll-like receptor pathway, chemokine signaling, apoptotic pathway, chromatin remodeling, protein transport, the immune microenvironment, and CD19-directed immunotherapy.

Keywords: Akt; BCL-2; CXCR4; PI3K; Syk; Waldenström macroglobulinemia; XPO1; mTOR.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / adverse effects
  • Antineoplastic Agents / therapeutic use*
  • Chromatin Assembly and Disassembly / drug effects
  • Drug Resistance, Neoplasm* / drug effects
  • Drug Resistance, Neoplasm* / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Humans
  • Mutation*
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism
  • Waldenstrom Macroglobulinemia* / drug therapy
  • Waldenstrom Macroglobulinemia* / genetics
  • Waldenstrom Macroglobulinemia* / metabolism
  • Waldenstrom Macroglobulinemia* / pathology

Substances

  • Antineoplastic Agents
  • Neoplasm Proteins