The objective of this real–world study was to evaluate treatment utilization, sequencing patterns, and associated healthcare resource utilization (HCRU) in patients with Waldenström macroglobulinemia (WM).

A retrospective observational analysis was conducted using the US Symphony Integrated Dataverse® database. Adults with ≥1 WM diagnostic code who initiated treatment between January 2020 and August 2025 were identified. Patients were categorized into eight mutually exclusive treatment–regimen groups, including bendamustine–based chemotherapy, rituximab monotherapy, other rituximab–based combinations, Bruton tyrosine kinase inhibitor (BTKi)–based regimens, bortezomib–based regimens, venetoclax–based regimens, and other therapies. Treatment utilization was analyzed overall, by calendar year, and by line of therapy (LOT), with sequencing patterns visualized using Sankey diagrams. All-cause HCRU during treatment (inpatient, outpatient, and other medical/hospital services) was examined and reported per-patient-per-year.

Among 7,583 patients who initiated first–line therapy, 29.7% progressed to second–line therapy and 12.9% to third or later lines. BTKi was the most commonly used drug class across all lines of therapy, with zanubrutinib used most frequently and with increasing utilization over time. In first–line therapy, bendamustine–based chemotherapy was most common (27.1%), followed by rituximab monotherapy (22.3%) and zanubrutinib (19.6%). In second– and third–line settings, rituximab monotherapy was the most commonly used regimen (19.9% and 20.3%, respectively), followed by BTKi–based regimens. Sequencing analyses showed that patients treated with first–line BTKi frequently received bendamustine–based chemotherapy as subsequent therapy (42.7% after first-line zanubrutinib, 22.2% after first-line ibrutinib), while those treated initially with bendamustine–based chemotherapy most often received BTKis in the second line (zanubrutinib 35.6%; ibrutinib 16.4%). Substantial HCRU was observed across LOTs. Outpatient visits per patient per year were lower for BTKi–based regimens compared with bendamustine–based or rituximab–based regimens across all lines of therapy. Mean inpatient visit rates were also lowest for BTKi–based regimens, while the highest inpatient utilization was observed with venetoclax– and bortezomib–based regimens.