Zanubrutinib versus fludarabine, cyclophosphamide and rituximab in fit, treatment-na¨ıve patients with chronic lymphocytic leukemia: a matchingadjusted indirect comparison

Aim

Fludarabine, cyclophosphamide and rituximab (FCR) is a first-line therapy for fit treatment-naive patients with chronic lymphocytic leukemia (CLL); however, its hematotoxicity and related infections necessitate more efficacious, safer treatments. Zanubrutinib is a highly potent and selective nextgeneration Bruton tyrosine kinase inhibitor approved for treatment-naive patients with CLL and small lymphocytic lymphoma. Given the absence of clinical trials providing head-to-head comparisons, the aim of this analysis was to conduct a matching-adjusted indirect comparison between zanubrutinib and FCR. Materials & methods: Patient-level data from SEQUOIA (zanubrutinib vs bendamustine + rituximab [BR]) was adjusted for interpopulation differences through propensity-score matching with aggregate data from the CLL10 trial (FCR vs BR). Progression-free survival (PFS) was compared among populations matched for immunoglobulin heavy-chain gene mutation, 11q deletion, β2-microglobulin, Binet stage and age. Sensitivity analyses incorporated geographic region, sex, creatinine clearance, the Cumulative Illness Rating Scale, Eastern Cooperative Oncology Group performance status and previous infections.