Future therapeutic options for patients with Waldenström macroglobulinemia.
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.
Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. Electronic address: jorgej_castillo@dfci.harvard.edu.
Jorge J
JJ
Castillo
Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Zachary R
ZR
Hunter
Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Guang
G
Yang
Division of Hematology and Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
Kimon
K
Argyropoulos
Division of Hematology and Oncology, Memorial Sloan-Kettering Cancer Center, New York, NY, USA.
M Lia
ML
Palomba
Bing Center for Waldenström Macroglobulinemia, Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA.
Steven P
SP
Treon
D051997:ADP-ribosyl Cyclase 1 / Q000235:genetics / Q000276:immunology; D000225:Adenine / Q000031:analogs & derivatives; D000077329:Agammaglobulinaemia Tyrosine Kinase; D002986:Clinical Trials as Topic; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000276:immunology; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000276:immunology; D010880:Piperidines; D011446:Prospective Studies; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000276:immunology; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000276:immunology; D011720:Pyrazoles / Q000627:therapeutic use*; D011743:Pyrimidines / Q000627:therapeutic use*; D019718:Receptors, CXCR4 / Q000235:genetics / Q000276:immunology; D008258:Waldenstrom Macroglobulinemia / Q000188:drug therapy* / Q000235:genetics / Q000276:immunology
C000595707:BCL2 protein, human; C527276:CXCR4 protein, human; C507779:MYD88 protein, human; D008562:Membrane Glycoproteins; D053594:Myeloid Differentiation Factor 88; D010880:Piperidines; D019253:Proto-Oncogene Proteins c-bcl-2; D011720:Pyrazoles; D011743:Pyrimidines; D019718:Receptors, CXCR4; C551803:ibrutinib; D011505:Protein-Tyrosine Kinases; D000077329:Agammaglobulinaemia Tyrosine Kinase; C000625949:BTK protein, human; C498154:CD38 protein, human; D051997:ADP-ribosyl Cyclase 1; D000225:Adenine
BCL2; BTK; CD38; CXCR4; MYD88; Waldenström