Ibrutinib monotherapy is approved for all lines of therapy in patients with WM, although its initial trial was focused on patients who relapsed, only (NCT01614821). Thus, clinical research on the use of ibrutinib monotherapy in the frontline setting of WM is warranted. At this year’s iwWM congress, Jorge Castillo presented long term data (4 years) of ibrutinib monotherapy in treatment-naïve WM patients.

Additionally to ibrutinib, to date the only once-daily BTK inhibitor approved in the USA and the European Union either as monotherapy or in combination with RTX for patients with WM [1], other BTKis, such as acalabrutinib and zanubrutinib, are now emerging as potential therapeutic alternatives. Acalabrutinib is an emergent, potent, and selective BTKi, which has received accelerated approval by the US FDA for the treatment of adult patients with relapsed or refractory (R/R) MCL and is in clinical development for CLL and DLBCL.

The open-label, multicenter, randomized phase III ASPEN trial was set up to assess the efficacy and safety of the potent, selective, irreversible next-generation BTK inhibitor zanubrutinib in Waldenström’s macroglobulinemia (WM). Cohort 1 of the study included patients with MYD88-mutated disease (n = 201); here, zanubrutinib was compared to ibrutinib after 1:1 randomization.

Many patients with WM require continuous treatment with BTK inhibitors, but difficult-to-manage AEs often lead to treatment discontinuation. Zanubrutinib is a potent and selective next-generation BTKi designed to minimize off-target kinase binding and associated side effects.

Waldenström’s macroglobulinemia (WM) is a low-grade non-Hodgkin B-cell lymphoplasmacytic lymphoma, characterized by the accumulation of clonal lymphoplasmacytic cells secreting monoclonal IgM protein in the bone marrow and other organs. WM is a lymphoma accounting for only 1–2 % of all hematologic tumors, with an annual incidence of three to four cases per million people in the USA and Europe, classifying it as a rare disease.