Current treatment options and investigational drugs for Waldenstrom’s Macroglobulinemia

ABSTRACT

Introduction: Waldenström’s Macroglobulinemia (WM) is a rare, indolent, incurable, low-grade B-cell lymphoplasmacytic neoplasm. This review article provides a modern clinical perspective of the individualized management of patients with symptomatic WM, in the context of the updated treatment guidelines and the currently available trial data.

Areas covered: Rituximab-based regimens (such as the dexamethasone, rituximab and cyclophosphamide combination, DRC) are the most widely used in the management of both newly diagnosed and relapsed/refractory patients with WM. Recently, the Bruton’s tyrosine kinase inhibitor ibrutinib has been licensed for use in WM with exciting results. Several investigational single agent and combination regimens are being evaluated for response, efficacy and tolerability in phase II clinical trials, including new generation monoclonal antibodies (ofatumumab), immunomodulatory agents (thalidomide and lenalidomide), proteasome inhibitors (bortezomib and carfilzomib), Bruton’s tyrosine kinase inhibitors (ibrutinib and acalabrutinib), phosphoinositide 3-kinase/protein kinase B (Akt)/mammalian target of rapamycin pathway inhibitors (everolimus and perifosene), and histone deacetylase inhibitors (panobinostat) both in the setting of newly diagnosed and relapsed/refractory disease.

Expert opinion: WM therapeutic approach should be individualized for each patient in accordance to the intensity of the disease characteristics, age, comorbidities, efficacy, tolerability and safety profile of each drug.

KEYWORDS:

• Waldenström’s Macroglobulinemia
• therapy
• rituximab
• ibrutinib
• investigational agents

Article highlights

• Waldenström Macroglobulinemia remains a rare and incurable disease.

• Patients with symptomatic disease should receive treatment to prevent end-organ damage and control disease-related symptoms.

• The intensity of the treatment choice depends on symptom severity, the need for rapid disease control, other factors such as age, comorbidities and cytopenias and the potential candidacy for autologous stem cell transplantation.

• Several new therapeutic options are now available for WM management but data based on randomized comparative trials are necessary to evaluate the role of each regimen in the frontline and relapsed/refractory WM setting, the sequence of therapeutic options and the role of transplantation.

• Novel agents can target pathways involved in the disease pathogenesis and therefore can broaden the WM treatment landscape.

This box summarizes key points contained in the article.

Declaration of interest

E. Terpos, E. Kastritis and M. Dimopoulos declare honoraria from Amgen and Janssen. 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.

Additional information

Funding

This paper was not funded.