A retrospective population-based study of long-term treatments and outcomes inwaldenstrom macroglobulinemia in Ontario, Canada

Abstract Introduction: Waldenstrom Macroglobulinemia (WM) is a rare B-cell malignancy characterized by periods of low burden disease not requiring treatment eventually leading to active disease requiring therapy. Treatment approaches have evolved over time including chemotherapy ± monoclonal antibodies such as rituximab and most recently targeted agents including Bruton Tyrosine Kinase Inhibitors. We sought to characterize treatments and real-world long-term outcomes in a contemporary cohort of Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma patients. Methodology: This was a retrospective population-based study in Ontario, Canada using linked administrative databases. All eligible patients >18 years diagnosed from 2005 to 2023 identified within the Ontario Cancer Registry were included. All provincially funded treatment regimens were documented; however, treatments funded by compassionate access, private insurance or investigational regimens as part of clinical trials were not captured. In total, n=1,986 patients identified as having either Lymphoplasmacytic Lymphoma or Waldenstrom Macroglobulinemia were included in this study. We evaluated outcomes including types of treatment, time to second line therapy and overall survival using the Kaplan Meier method. Results: Out of the 1,986 patients with Waldenstrom Macroglobulinemia/Lymphoplasmacytic Lymphoma included in the cohort, the median age was 73 (IQR: 64-80) and 39% were female. Patients were followed for a median of 4 years (IQR: 2-8). In total, 55% of patients (n=1,093) received provincially funded treatment for Waldenstrom's during the follow-up period; median Kaplan Meier estimate of time from diagnosis to first-line treatment was 1.9 years. Of those who received frontline therapy, 52% of patients (n=569) went on to receive rituximab maintenance therapy and 23% of patients (n=250) went on to receive second-line treatment; median Kaplan Meier estimate of time to second line therapy was over 13 years. In total, 80 patients (4% of the overall cohort and 7% of those who received frontline therapy) received three or more lines of treatment. In total, 37% (n=727) of patients died within with the follow-up period, with median Kaplan Meier survival estimate of 9.9 years after diagnosis. The most common frontline treatment regimens (each +/- anti-CD20 antibody) were Bendamustine (60%), CVP (21%), Bruton Tyrosine Kinase inhibitor (5%), rituximab monotherapy (5%), Chlorambucil (4%) or CHOP (2%). Comparison of overall survival, time to second line therapy and depth of response based on IgM for different treatment regimens is under active investigation. Conclusion: We characterized real-world long-term outcomes in a large population-based cohort of Waldenstrom's patients. Newly diagnosed patients over the past two decades have received multiple frontline treatment regimens and overall have robust long-term survival outcomes.