Waldenström macroglobulinemia: from biology to treatment

Abstract

Waldenström macroglobulinemia (WM) is distinct B-cell lymphoproliferative disorder primarily characterized by bone marrow infiltration of lymphoplasmacytic cells along with production of a serum monoclonal (IgM). In this review, we describe the biology of WM, the diagnostic evaluation for WM with a discussion of other conditions that are in the differential diagnosis and clinical manifestations of the disease as well as current treatment options. Within the novel agents discussed are everolimus, perifosine, enzastaurin, panobinostat, bortezomib and carfilzomib, pomalidomide and ibrutinib. Many of the novel agents have shown good responses and have a better toxicity profile compared to traditional chemotherapeutic agents, which makes them good candidates to be used as primary therapies for WM in the future.

Keywords::

• biology
• Bruton's tyrosine
• kinase
• MYD88
• treatment
• Waldenström macroglobulinemia

Financial & competing interests disclosure

IM Ghobrial is on the advisory board for Onyx, BMS and Celgene and receives research lab support from Genzyme and BMS. SP Treon receives research support from honoraria, and consulting fees from Pharmacyclics, Janssen Pharmacuticals and Onyx Pharmaceuticals. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript

Key issues

• Recent findings demonstrated that MYD88/IL-1 receptor-associated kinase (IRAK) signaling pathway might have a critical role in pathogenesis of Waldenström macroglobulinemia (WM).

• Somatic mutations in MYD88 are found in over 90% of WM patients, which may help to differentiate WM from other B-cell malignancies.

• Current research efforts in inhibition of Bruton's tyrosine kinase (BTK) and IRAK signaling might provide better treatment strategy for WM.

• Many treatment options are available for WM patients and some of these include rituximab, bortezomib, cyclophosphamide and nucleoside analogs fludarabine and cladribine which are less commonly used.

• Novel agents under study are showing promising results as a single agent or in combination. Some of these include everolimus, ibrutinib as well as the newer proteasome inhibitors carfilzomib and oprozomib.

• There is a need for studies with progression-free survival and overall survival as end points combined with quality-of-life assessment as well as randomized Phase III studies to evaluate the benefit of different treatments for patients with WM.

Notes