Second Primary Malignancies and Disease Transformation in Patients With Symptomatic Waldenström's Macroglobulinemia.

Background: Waldenstrom macroglobulinemia (WM) is an indolent lymphoma with a long course; advanced age and immunosuppressive treatments may predispose for second primary malignancies (SPM).

Methods: Consecutive symptomatic, newly diagnosed patients with WM who were diagnosed, treated and followed-up until May 28, 2024 were included in this study.

Results: 677 symptomatic patients with WM were included in the analysis; their median age was 69 years (range 24-93) and 209 were females (30.9%). Over a median follow-up of 5.32 years (range 0.01-25.61), 58 patients (8.6%) were diagnosed with a SPM. The median time from WM diagnosis to SPM diagnosis was 4.93 years (range 0.07-20.71). The incidence rate (IR) of a SPM per person-year was 0.009, translating to roughly 1 case per 100 person-years. The cumulative incidence (CI) of SPMs, accounting for death due to WM or other causes as a competing event, at 5 and 10 years was 4.0% and 7.2%. Furthermore, 23 patients (3.4%) developed transformation to high grade lymphoma. The median time from WM diagnosis to transformation was 5.36 years (range 0.01-25.6). The IR of transformation per person-year was 0.003, translating to 3 cases per 1000 person-years. The CI of transformation to high-grade lymphoma, accounting for death due to WM or other causes as a competing event, at 5 and 10 years, was 2.1% and 3.4%.

Conclusions: Data from our prospectively maintained multicenter database revealed that 8.6% and 3.4% of symptomatic patients with WM developed a SPM and disease transformation, respectively, over a median follow-up of 5.3 years.