Real-World Outcomes Among Medicare Beneficiaries Treated with Bruton Tyrosine Kinase Inhibitors for Treatment-Naïve...

There is a dearth of head-to-head studies comparing covalent Bruton tyrosine kinase (cBTK) inhibitors in adults with chronic lymphocytic leukemia (CLL). Real-world evidence may complement clinical trial data by assessing relative effectiveness in routine practice. This retrospective observational study used a de-identified Medicare Fee-For-Service database to compare real-world outcomes associated with first-line cBTKi monotherapies in older adults with CLL.

Patients aged ≥ 65 years with CLL initiating first-line ibrutinib, acalabrutinib, or zanubrutinib monotherapy between January 1, 2020 and September 30, 2025 were included. Real-world time to treatment discontinuation (rwTTD), time to next treatment (rwTTNT), and overall survival (rwOS) were evaluated using Kaplan-Meier analyses and Cox proportional hazards models. Subgroup analyses were performed by age group.

Among 10,523 patients included, 3006 (28.6%) received zanubrutinib (median follow-up 15.8 months), 4309 (40.9%) received acalabrutinib (20.7 months), and 3208 (30.5%) received ibrutinib (34.9 months). Median rwTTD was not reached (NR) for zanubrutinib, compared with 24 months for acalabrutinib and 14 months for ibrutinib. Median rwTTNT was NR for zanubrutinib, 40 months for acalabrutinib, and 20 months for ibrutinib. After adjustments for age, sex, race, CCI, and year of index, zanubrutinib had significantly longer rwTTD (hazard ratio [HR] 0.57 [95% CI 0.51-0.61]), rwTTNT (HR 0.63 [0.55-0.71]), and rwOS (HR 0.64 [0.54-0.77]) compared to ibrutinib. Zanubrutinib also had significantly improved rwTTD (HR 0.86 [0.78-0.94]), rwTTNT (HR 0.87 [0.78-0.96]), and rwOS (HR 0.77 [0.66-0.88]) compared to acalabrutinib. Similar patterns were observed when stratified by age group over 65.

These findings demonstrate that zanubrutinib is associated with improved real-world outcomes compared with other cBTK inhibitors.