Reducing treatment toxicity in Waldenström macroglobulinemia

ABSTRACT

Introduction: Waldenström macroglobulinemia (WM) is a rare subtype of non-Hodgkin lymphoma characterized by the presence of IgM-secreting clonal lymphocytes, plasma cells, and lymphoplasmacytic cells. Many well-established treatment options are available for patients with WM. However, a unique array of side effects may occur in patients during therapy related to the underlying disease, as well as the chosen treatment regimen.

Areas covered: This review summarizes the most common adverse effects that occur during treatment of WM, as well as potential strategies to decrease the risk of toxicity.

Expert opinion: There are multiple highly effective treatment options for patients with WM. All these treatment options, however, can be associated with a variety of adverse events. For example, chemotherapy has been associated with the development of myeloid neoplasms, anti-CD20 monoclonal antibodies with paradoxical IgM flares and infusion reactions, proteasome inhibitors with neuropathy, and BTK inhibitors with bleeding and cardiac arrhythmias. Dose reductions, lower number of cycles and changes in route of administration are some of the tools a clinician has available for managing and minimizing toxicity. Future research will focus on improving patient safety without sacrificing the efficacy of treatment.

KEYWORDS:

• Chemotherapy
• proteasome inhibitors
• BTK inhibitors
• monoclonal antibodies
• safety
• toxicity
• Waldenström macroglobulinemia

Article highlights

• There are several effective and safe options for the treatment of Waldenström macroglobulinemia although patients should be closely monitored during therapy for the emergence of treatment-specific side effects.

• Reduction in the number of rituximab-bendamustine treatment cycles may prevent toxicity without compromising disease outcomes.

• The frequency of bortezomib dosing and the manner of administration can be altered to decrease the risk of peripheral neuropathy in patients with Waldenström macroglobulinemia.

• Patients with Waldenström macroglobulinemia have a unique side effect profile associated with rituximab, including increased risk of rituximab intolerance and IgM flares.

• Ibrutinib is an effective treatment for Waldenström macroglobulinemia with a medically manageable side effect profile that includes atrial fibrillation and bleeding. Newer BTK inhibitors such as zanubrutinib and acalabrutinib show similar activity levels with differences in side-effect profile.

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Declaration of interest

JJ Castillo declares relationships with Abbvie, Beigene, Jannsen, Pharmacyclics, Roche and TG Therapeutics. SP Treon declares relationships with Beigene, BMS, Janssen, Pharmacyclics and X4 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. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

Reviewer disclosures

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

Additional information

Funding

This paper was not funded.