Updates in the Treatment of Mantle Cell Lymphoma: A Canadian Expert Framework
Waldenström macroglobulinemia (WM) is an indolent B-cell non-Hodgkin lymphoma (NHL) characterized by malignant B cells that produce IgM monoclonal protein. Like other indolent B-cell NHLs, treatment is indicated when patients are symptomatic with lymphadenopathy, splenomegaly or have detrimental cytopenias, but uniquely hyperviscosity and other complications related to gammopathy may present a need for treatment1. Currently in Canada chemoimmunotherapy using bendamustine and rituximab (BR) is the favored therapeutic combination for treatment-naïve patients with WM due to a superior efficacy and toxicity profile compared to rituximab plus CHOP2 and a fixed duration schedule3. The availability of Bruton’s tyrosine kinase inhibitors (BTKi) have transformed the treatment landscape for patients with WM, particularly in the relapsed setting. Ibrutinib, a once-daily BTKi, was approved by Health Canada (HC) for WM in 2016 based on two non-randomized studies showing high response rates in heavily pretreated rituximab-refractory patients with sustained efficacy (86% progression-free survival (PFS) at 18 months) and acceptable tolerability4,5. Ibrutinib forms an irreversible covalent bond to the cysteine residue (C481) at the active binding site of BTK6. Patients with mutated MYD88 (MYD88MUT),
who represent over 90% of patients with WM, have a higher rate of response with ibrutinib than those without (MYD88WT)4,7,8.
Aside from its impressive efficacy, its oral administration offers a major advantage in terms of convenience for patients and lower administrative costs for publicly funded health care systems such as in Canada.