A safety profile of medications used to treat Waldenström’s macroglobulinemia

ABSTRACT

Introduction: Waldenström’s macroglobulinemia (WM) is a B-cell lymphoproliferative disease with serum IgM monoclonal component and bone marrow infiltration by lymphoplasmacytic lymphoma. Traditional therapy was based on that regimens used for closely related entities, such as chronic lymphocytic leukemia or multiple myeloma. This resulted in a lack of drugs specifically approved for WM, until the discovery of the Bruton Tyrosine Kinase (BTK) inhibitors.

Areas covered: Two main therapeutic attitudes are possible: (1) conventional therapies based on combinations with alkylating agents or proteasome inhibitors with steroids and anti-CD20 monoclonal antibodies or (2) new approaches with BTK inhibitors, usually alone. Other possibilities such as BCL2 inhibitors, PI3K/AKT inhibitors, and others are currently under evaluation, but we will focus the review on the most consolidated approaches that are available for patients with WM at different stages of the disease. PubMed, Web of Science, and clinicaltrials.gov were queried for the keywords ‘Waldenstrom macroglobulinemia’ and the different drugs here evaluated through 1 February 2018.

Expert opinion: Although WM has no many specific drugs, there are many possible therapies, including Ibrutinib, the first formally approved drug for this disorder.

KEYWORDS:

• Waldenström macroglobulinemia
• anti-cd20
• proteasome inhibitor
• dexamethasone
• cyclophosphamide
• bendamustine
• IMiDs
• BTK inhibitors

Article highlights

• Waldenström’s macroglobulinemia therapy has considerably changed in the last 10 years which requires new formation in the field, for both efficacy and toxicity management

• Highly toxic drugs (nucleoside analogs, high-dose therapy, etc.) have been relegated several steps in the therapeutic scale

• MoAb anti-CD20 and BTK inhibitors form the backbone of the current therapy in Waldenström’s macroglobulinemia

• Major concerns about MoAbs are intravenous infusion and infusion reactions, tumor flare, and long-term immunosupression

• Major concerns about ibrutinib are hemorrhagic problems, atrial fibrillation, and fungal infections in the long-term use

• Most promising therapies for future are drug combinations and second-generation BTK inhibitors.

Declaration of interest

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. Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

Funding support has been given by the employer of the authors (University Hospital of Salamanca) and the following grant supports: Sociedad Castellano-Leonesa de Hematología y Hemoterapia (FUCALHH 2015) and the Gilead Sciences (GILEAD) Fellowship Program (GLD16/00162), as well as funds from the Instituto de Salud Carlos III (ISCIII), Spanish Ministry of Economy and Competitiveness, CIBERONC-CB16/12/00233. MES was funded by the "Miguel Servet Programme (CP13/00080)" from ISCIII. CJ is supported by the "Beca de investigación FEHH-CRIS 2018"