Burden and survival outcome of secondary malignancies in Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL): A population-based analysis using Surveillance, Epidemiology, and End Results (SEER 2000-2022).

Abstract

e19094 Background: WM/LPL is an indolent B-cell Non-Hodgkin Lymphoma with prolonged survival and predisposition to secondary malignancies (SM) influencing clinical outcomes and survivorship care. We evaluated the incidence, demography, treatment utilization, and outcomes of SM in patients with WM/LPL using population-based data. Methods: SEER-22 database was used to identify patients with LPL/WM diagnosed between 2000–2022 and stratified by SM. Overall survival (OS) was analyzed using Kaplan–Meier survival analysis and propensity score matched Cox regression was used to assess mortality risk. Hazard ratios were reported, with p<0.05 deemed significant. Results: 22,170 patients with WM/LPL were identified, with a median age of 71 years (IQR 16); the cohort was predominantly male (59.0%), White (84.0%), had a median household income of $50,000–$75,000 (48.9%), and resided primarily in urban areas (89.5%). Among all WM/LPL patients, 20.8% (n=4,615) developed a SM. Patients who developed SM were older than those without (median age 75 vs 70 years, p<0.0001) with 45.2% alive at predefined follow-up. The most common solid organ SM were gastrointestinal adenocarcinoma (16%), prostate cancer (14%), and lung adenocarcinoma (9%), while the leading hematologic SM were plasma cell myeloma (6%), diffuse large B-cell lymphoma (5%), and myelodysplastic syndrome (2%). 35.3% of the cohort received chemotherapy, while 0.1% received cancer-related surgery or radiation. On multivariable analysis, older age (OR 0.82, 95% CI 0.81–0.83), male sex (OR 0.59, 95% CI 0.44–0.80), urban residence (OR 1.99, 95% CI 1.24–3.18), and higher income (OR 2.16, 95% CI 1.13–4.15) were significantly associated with SM diagnosis. Kaplan–Meier analysis demonstrated inferior survival among patients with SM (54.8% vs 45.2%, p<0.0001), with shorter median OS (9 vs 14 years, log-rank p<0.001). Similarly, Propensity-matched analysis revealed worse OS in patients with SM (HR 1.15, 95% CI 1.09–1.22, p<0.001). Median OS varied substantially by SM site (see Table). Conclusions: Our study demonstrates a substantial burden of SMs among patients with WM/LPL and are associated with substantially inferior survival despite the indolent nature of the disease. The marked heterogeneity in SM types and outcomes highlights the need for risk-adapted surveillance, survivorship-focused care, and equitable strategies to address disparities and improve long-term outcomes in this population. SM Site Median OS (years) IQR p-value Hepatopancreatobiliary 1 0 <0.05 CNS 3.5 9 <0.05 Breast 3 6 <0.05 Colorectal 4 3.5 <0.05 Lymph Node 5 8 <0.05 Blood 6 7 <0.05 Lung 7 9 <0.05 Head & Neck 6.5 8.5 <0.05 Melanoma 9 10 <0.05 Urogenital 10.5 7 <0.05