Treatment Patterns and Outcomes in a Nationwide Cohort of Older and Younger Veterans with Waldenström Macroglobulinemia, 2006–2019

SIMPLE SUMMARY: Waldenström macroglobulinemia is a rare cancer about which little is known. Evidence from real-world settings provides invaluable information to patients and clinicians, especially for older and/or frailer patients, a demographic often excluded from clinical trials. This study provides information about treatment patterns and outcomes from real-world cohorts of older (>70 years) and younger (≤70 years) patients. We report findings across early (2006–2012) and modern (2013–2019) eras, reflecting a transition during which the number of treatments available for Waldenström macroglobulinemia rapidly increased. We found marked improvements in treatment outcomes among older patients in the modern vs early era, with little or no improvement in outcomes among younger patients. Our findings emphasize the importance of real-world evidence in guiding patient-specific treatment decisions. ABSTRACT: Little is known about real-world treatment patterns and outcomes in Waldenström macroglobulinemia (WM) following the recent introduction of newer treatments, especially among older adults. We describe patterns of first-line (1 L) WM treatment in early (2006–2012) and modern (2013–2019) eras and report outcomes (overall response rate (ORR), overall survival (OS), progression-free survival (PFS), and adverse event (AE)-related discontinuation) in younger (≤70 years) and older (>70 years) populations. We followed 166 younger and 152 older WM patients who received 1 L treatment between January 2006 and April 2019 in the Veterans Health Administration. Median follow-up was 43.5 months (range: 0.6–147.2 months). Compared to the early era, older patients in the modern era achieved improved ORRs (early: 63.8%, modern: 72.3%) and 41% lower risk of death/progression (hazard ratio (HR) for PFS: 0.59, 95% CI (confidence interval): 0.36–0.95), with little change in AE-related discontinuation between eras (HR: 0.82, 95% CI: 0.4–1.7). In younger patients, the AE-related discontinuation risk increased almost fourfold (HR: 3.9, 95% CI: 1.1–14), whereas treatment effects did not change between eras (HR for OS: 1.4, 95% CI: 0.66–2.8; HR for PFS: 1.1, 95% CI: 0.67–1.7). Marked improvements in survival among older adults accompanied a profound shift in 1 L treatment patterns for WM.