Clinical outcomes in newly diagnosed patients with Waldenström's macroglobulinaemia treated in a tertiary academic centre

Summary Waldenström's macroglobulinaemia ( WM ) is a rare B‐cell lymphoproliferative disorder with multiple effective front‐line treatment options. However, real‐world comparative data on commonly used regimens are limited. We conducted a retrospective cohort study of 348 consecutive, newly diagnosed WM patients treated between 2002 and 2024. Patients received first‐line therapy with either bortezomib–dexamethasone–rituximab ( BDR , n = 35), Bruton's tyrosine kinase inhibitors ( BTKis , n = 57) or dexamethasone–rituximab–cyclophosphamide ( DRC , n = 256). BTKi demonstrated the highest MRR (major response rate, ≥ PR ) (80.7%), followed by DRC (68.4%) and BDR (40.0%) ( p < 0.001). The median PFS and OS did not differ significantly among regimens. TTNT seemed to be longer in the BTKi group (log‐rank p = 0.025), with a 74% reduced risk of salvage therapy compared to DRC ( aHR = 0.26, p = 0.016). Cumulative WM ‐related mortality at 5 years was lowest in BTKi ‐treated patients (4.1% vs. 13.0% DRC vs. 17.1% BDR ), though differences were not statistically significant. In this single‐centre analysis, both BTKi and DRC led to prolonged disease control in the upfront treatment of patients with WM . Extended follow‐up and prospective validation are needed to reveal potential long‐term survival differences.