Presentation (CTI)

OBJECTIVES: Randomized clinical trials establish efficacy and safety at regulatory approval; however, important uncertainties regarding treatment persistence, tolerability, and comparative effectiveness often remain. As health technology assessment (HTA), payer, and treatment decisions increasingly incorporate real-world evidence (RWE), continuous monitoring of post-marketing outcomes has become increasingly important. This study used a REAL-SLR to evaluate evolving safety and treatment persistence outcomes for zanubrutinib in CLL and assess how post-marketing evidence complements pivotal trial findings.
METHODS: RWE studies reporting safety, discontinuation, time to discontinuation (TTD) or time to next treatment (TTNT) outcomes for zanubrutinib in CLL were identified through the continuously-updated REAL-SLR. Protocol-defined searches of publications and major conference abstracts were updated daily. Eligible studies were mapped by study design, geography, sample size, population characteristics, treatment pathway and drug class. Outcomes included adverse events (AEs), cardiovascular AEs, infections, discontinuations, TTD, and TTNT.
RESULTS: Of 40 studies including zanubrutinib-treated patients, 19 reported outcomes of interest and compared zanubrutinib with acalabrutinib/ibrutinib. Among six studies reporting TTNT, zanubrutinib showed significant improvement versus ibrutinib (2/2 studies) and acalabrutinib (4/6 studies). Among five studies reporting TTD, zanubrutinib showed longer TTD versus ibrutinib (4/5 studies) and acalabrutinib (3/3 studies). Discontinuation rates were lower with zanubrutinib than ibrutinib and acalabrutinib (49.2%-58.7%/56.6%-74.7%/39.0%-66.3% at 24-month, respectively). Atrial fibrillation rates were comparable to acalabrutinib (7.18% vs 7.98%; 11% vs 13% at one year) and lower than ibrutinib (11% vs 16%/8.0% vs 10.4%), though one study showed higher rates versus acalabrutinib (4.2% vs 2.3%). Rates of cardiovascular AEs were similar/numerically-lower with zanubrutinib than acalabrutinib (14.5% vs 21.0%).
CONCLUSIONS: Living RWE surveillance identified favorable treatment persistence and comparable or improved cardiovascular safety outcomes for zanubrutinib relative to other BTK inhibitors. Continuous evidence monitoring may reduce post-approval uncertainty, support comparative value assessment, and provide decision-makers with timely evidence for HTA, reimbursement, and treatment selection in CLL.