Descriptive epidemiology of Waldenström macroglobulinemia (WM): Demographics, outcomes, and predictors of survival in the US community oncology setting.

7064 Background: WM is a rare, indolent subtype of non-Hodgkin lymphoma (NHL), comprising <2% of annual U.S. NHL cases. Natural history studies and registries often lack sufficient patient-level data about treatment patterns and outcomes. This study describes demographics, clinical characteristics, and outcomes of patients with WM treated in the community oncology setting. Methods: This retrospective cohort study included adults diagnosed with WM in the U.S. Oncology Network from 2014 to 2022, with follow-up through 2023. Data were sourced from the iKnowMed electronic health record system. Structured data were used to assess patient characteristics and overall survival (OS). Chart abstraction was performed on a random subset (n=200) to evaluate treatment characteristics and outcomes (i.e. OS, time to next treatment (TTNT), and real-world progression-free survival (rwPFS)). Multivariable Cox proportional hazard models evaluated factors associated with these outcomes. Results: Among 2,554 patients with WM (mean age: 72.7 years, SD: 10.1), majority were male (58.9%), and White (77.3%), consistent with SEER data reflecting the indolent nature of WM, with 82.1% alive at study conclusion and median OS was not reached. At 5-years, OS probabilities stratified by Modified Staging System for WM (MSS-WM) were 96.4% (low risk, N=135), 87.3% (low-intermediate risk, N=237), 69.2% (intermediate risk, N=267), and 50.9% (high risk, N=278; p < 0.0001), aligning with the externally validated MSS-WM model, demonstrating its utility in risk stratification. In the subset of 200 patients, 8.5% (N=17) had smoldering WM, and 23% (N=46) experienced disease progression. MYD88 L265P and CXCR4 mutations were present in 85.4% and 29% of patients, respectively, consistent with reported case series. Most (78%) patients initiated LOT 1 therapy. Treatment patterns aligned with NCCN guidelines, with BTK inhibitors and Rituximab-based regimens comprising 98% of LOT 1 therapies. In the multivariable model, area deprivation index was significantly linked to poorer OS (HR: 12.8, CI: 2.6–63.4), shorter TTNT (HR: 2.2, CI: 1.1–6.3) and worse rwPFS (HR: 4.1, CI: 1.2–14.3). Patients with a Charlson Comorbidity Index score ≥2, were more likely to discontinue treatment (HR: 2.2, CI: 1.3–3.5) and progress to next therapy (HR: 2.2, CI: 1.2–4.0). Conclusions: This natural history study of patients with WM treated in the community oncology setting confirms WM’s indolent nature, with long survival and effective risk stratification using the MSS-WM. Real-world treatment patterns aligned to guidelines, while area-level socioeconomic factors and comorbidities highlighted disparities impacting outcomes. These findings emphasize the need for tailored, equitable care strategies and provide insights to enhance treatment approaches and address unmet needs in patients with WM.