Investigators Report Survival, Cost-effectiveness Data for Zanubrutinb

Treatment with zanubrutinib vs bendamustine-rituximab (BR) or dexamethasone-rituximab-cyclophosphamide (DRC) in patients with Waldenström macroglobulinemia (WM) has demonstrated longer survivals, and zanubrutinib appears more cost-effective than ibrutinib, according to poster presentations at the European Hematology Association 2021 Virtual Congress.

WM is a rare, indolent B-cell lymphoma that is generally treated with rituximab-based regimens or Bruton tyrosine kinase (BTK) inhibitors.

Survival Findings

To compare progression-free survival (PSF), overall survival (OS), and adverse events (AEs) between regimens, investigators used matching-adjusted indirect comparisons (MAICs) to match and compare data for 101 patients with WM (83 relapsed/refractory, 19 treatment-naïve) treated with zanubrutinib in the ASPEN trial with 71 relapsed/refractory patients treated with BR, and 72 treatment-naïve patients treated with DRC.¹

MAICs carry the limitation of not being able to completely adjust for all unobserved and unreported baseline patient characteristics.

Investigators said zanubrutinib vs DRC demonstrated significantly longer 12- and 24-month PSF (92% vs 85% and 90% vs 68%, respectively), longer 12- and 24-month OS (95% vs 92% and 94% and 85%), and a higher incidence of neutropenia (14.3% vs 9.7%). The postmatching HR for zanubrutinib PFS was 0.35 (95% CI, 0.14-0.86) and OS was 0.47 (95% CI, 0.14-1.62).

Zanubrutinib vs BR demonstrated significantly longer 12- and 24-month PFS (94% vs 79% and 81% vs 59%, respectively) and 12- and 24-month OS (98% vs 87% and 88% vs 77%), along with significantly lower incidence of neutropenia (17.5% vs 35.2%).

The postmatching HR for Zanubrutinib vs BR PFS was 0.37 (95% CI, 0.15-0.91) and OS was 0.29 (95% CI, 0.10-0.85).

Zanubrutinib Cost-Effectiveness

Investigators concluded zanubrutinib appears to be cost-effective vs ibrutinib for US patients with WM who have received ≥ 1 prior therapy or as first-line treatment.²

They estimated savings based on life-years (LYs), quality-adjusted life-years (QALYs), and costs for each treatment over 30 years, basing OS, PFS, and time-to-discontinuation on data from the ASPEN trial. Costs considered included drug acquisition, management of adverse events, and terminal care.

Findings demonstrated 0.94 LY and 0.84 QALY gained for patients treated with zanubrutinib vs ibrutinb and an incremental cost of $11,132 for zanubrutinib treatment, based on costs associated with extended treatment for zanubrutinib vs ibrutinib ($1,547,630 vs $1,536,498, respectively).

Total LYs for zanubrutinib vs ibrutinib were 11.33 vs 10.39, respectively, and total QALYs were 8.75 vs 7.90.

With its longer time to treatment failure and a lower monthly drug acquisition cost, zanubrutinb reduces costs of disease management by $2935 and other direct costs by $2964 vs treatment with ibrutinib, the authors said. The incremental cost-effectiveness ratio for QALY gained was $13,205, according to the study.

Investigators said that at a willingness-to-pay threshold of $100,000 per QALY gained, the probability of zanubrutinib being cost-effective was 61%.

A limitation of this economic analysis was the immature survival data from ASPEN, the authors said.

References

1. Castillo J, Yang K, Liu R, et al. Efficacy and safety of zanubrutinib versus rituximab-based chemotherapy in Waldenström macroglobulinemia: matching-adjusted indirect comparisons. Presented at: EHA2021 Virtual Congress. Abstract EP805.

2. Castillo J, Yang K, Liu R, et al. Cost-effectiveness of zanubrutinib versus ibrutinib in adult patients with Waldenström macroglobulinemia. Presented at: EHA2021 Virtual Congress. Abstract EP1174.