Future therapeutic options for patients with Waldenström macroglobulinemia

Jorge J Castillo; Zachary R Hunter; Guang Yang; Kimon Argyropoulos; M Lia Palomba; Steven P Treon

doi:10.1016/j.beha.2016.08.021

Future therapeutic options for patients with Waldenström macroglobulinemia

Best Pract Res Clin Haematol. 2016 Jun;29(2):206-215. doi: 10.1016/j.beha.2016.08.021. Epub 2016 Sep 14.

Authors

Jorge J Castillo¹, Zachary R Hunter², Guang Yang², Kimon Argyropoulos³, M Lia Palomba³, Steven P Treon²

Affiliations

¹ Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: jorgej_castillo@dfci.harvard.edu.
² Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
³ Division of Hematology and Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.

PMID: 27825467
DOI: 10.1016/j.beha.2016.08.021

Abstract

Waldenström macroglobulinemia (WM) is a rare lymphoma characterized by the accumulation of IgM-producing lymphoplasmacytic cells. Although WM patients can experience prolonged remissions, the disease invariably recurs. Therefore, novel treatments associated with higher success rates and lower toxicity profiles are needed. The discovery of recurrent mutations in the MYD88 and CXCR4 genes has unraveled potential therapeutic targets in WM patients. As a result of these findings and based on the design and execution of a prospective clinical trial, the FDA granted approval to ibrutinib, an oral Bruton tyrosine kinase (BTK) inhibitor, to treat patients with symptomatic WM. The present review focuses on potential therapies that could change the landscape of treatment of patients with WM, specifically focusing on inhibitors or antagonists or the proteasome, BTK, CD38, BCL2 and the CXCR4 and MYD88 genes themselves. Novel agents with novel mechanisms of action should be evaluated in the context of carefully designed clinical trials.

Keywords: BCL2; BTK; CD38; CXCR4; MYD88; Waldenström.

Publication types

Review

MeSH terms

ADP-ribosyl Cyclase 1 / genetics
ADP-ribosyl Cyclase 1 / immunology
Adenine / analogs & derivatives
Agammaglobulinaemia Tyrosine Kinase
Clinical Trials as Topic
Humans
Membrane Glycoproteins / genetics
Membrane Glycoproteins / immunology
Myeloid Differentiation Factor 88 / genetics
Myeloid Differentiation Factor 88 / immunology
Piperidines
Prospective Studies
Protein-Tyrosine Kinases / antagonists & inhibitors
Protein-Tyrosine Kinases / genetics
Protein-Tyrosine Kinases / immunology
Proto-Oncogene Proteins c-bcl-2 / genetics
Proto-Oncogene Proteins c-bcl-2 / immunology
Pyrazoles / therapeutic use*
Pyrimidines / therapeutic use*
Receptors, CXCR4 / genetics
Receptors, CXCR4 / immunology
Waldenstrom Macroglobulinemia / drug therapy*
Waldenstrom Macroglobulinemia / genetics
Waldenstrom Macroglobulinemia / immunology

Substances

BCL2 protein, human
CXCR4 protein, human
MYD88 protein, human
Membrane Glycoproteins
Myeloid Differentiation Factor 88
Piperidines
Proto-Oncogene Proteins c-bcl-2
Pyrazoles
Pyrimidines
Receptors, CXCR4
ibrutinib
Protein-Tyrosine Kinases
Agammaglobulinaemia Tyrosine Kinase
BTK protein, human
CD38 protein, human
ADP-ribosyl Cyclase 1
Adenine