OBJECTIVES: The first-in-class Bruton tyrosine kinase inhibitor (BTKi), ibrutinib, follow-on BTKi zanubrutinib, and rituximab-based regimens are among the first-line (1L) treatments for Waldenström macroglobulinemia (WM) approved by the US Food and Drug Administration. This study evaluated the clinical benefit and associated treatment-related costs using published clinical trial data and real-world evidence.

METHODS: A semi-Markov simulation model was constructed to estimate the clinical outcomes and cost of 1L treatment with ibrutinib, zanubrutinib, and rituximab-based regimens, including bendamustine+rituximab (BR) for patients with WM in the 1L setting from a US Medicare perspective. The model incorporated treatment-specific progression-free survival, overall survival, safety, and tolerability data based on published clinical trials. Routine care-related costs (treatment-related and disease-state specific) and adverse event (AE) costs were reported as per treatment patient per month (PTPPM). AE PTPPM costs from 1-year clinical trial results were applied to a 1-year time horizon. Scenario analyses examined the impact of real-world ibrutinib dose reduction (DR) on outcomes based on different clinical trials. Overall survival estimates were based on trials with small populations in the rare WM disease state, where median survival was not met.

RESULTS: Among modeled patients with WM in the 1L setting, average undiscounted progression-free years over 1-year/5-year time horizons for ibrutinib, zanubrutinib, and BR were 0.97/4.16, 0.92/3.40, and 0.94/3.77, respectively. Average undiscounted total life years for ibrutinib, zanubrutinib, and BR were 0.998/4.85, 0.95/3.81, and 0.98/4.54, respectively. Discounted routine care costs were $60/$62, $59/$61, and $61/$64; AE-related costs were $677, $820, and $1064, respectively. Ibrutinib DR resulted in a 20.2% drop in AE PTPPM costs to $540 among patients who may be eligible for DR following an AE.

CONCLUSIONS: Using base case assumptions and conservative estimates of clinical effectiveness from package inserts and pivotal trial publications, modeled clinical outputs suggest similar clinical benefits across WM treatments in 1L settings.