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August 23, 2026Journal of Comparative Effectiveness ResearchOpen Access

Zanubrutinib versus fludarabine, cyclophosphamide and rituximab in fit, treatment-naïve patients with chronic lymphocytic leukemia: a matching-adjusted indirect comparison

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Authors

TMTalha MunirLBLianne BarniehLMLeyla Mohseninejad

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Overview

Matching-adjusted indirect comparison shows superior progression-free survival with zanubrutinib versus FCR in fit chronic lymphocytic leukemia, supporting its use as first-line therapy.

Key Points

  • To compare progression-free survival between zanubrutinib and standard chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab (FCR) in fit, treatment-naïve patients with chronic lymphocytic leukemia.
  • Conducted a matching-adjusted indirect comparison using individual patient data from the SEQUOIA trial (zanubrutinib arm) and published aggregate data from the CLL10 trial (FCR arm).
  • Balanced baseline characteristics between cohorts using propensity score weighting for immunoglobulin heavy-chain gene mutation, 11q deletion, β2-microglobulin, Binet stage, and age.
  • Performed sensitivity analyses incorporating region, sex, creatinine clearance, Cumulative Illness Rating Scale score, ECOG performance status, and history of infections.
  • Primary matched analysis demonstrated superior progression-free survival with zanubrutinib compared with FCR (HR 0.41, 95% CI: 0.20–0.81; effective sample size = 174).
  • Sensitivity analyses adjusting for geographic region, ECOG performance status, or previous infections showed consistent progression-free survival benefits for zanubrutinib.
  • Adjusting for Cumulative Illness Rating Scale (HR 0.45, 95% CI: 0.16–1.24; effective sample size = 64) or creatinine clearance (HR 0.52, 95% CI: 0.24–1.13; effective sample size = 123) showed numerically favorable progression-free survival for zanubrutinib.

Cite This Study

Munir et al. (2026) studied this question.

synapsesocial.com/papers/6a8aae007677a34114446a4ehttps://doi.org/10.57264/cer-2025-0192
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Also Consider

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  5. 5Adverse event profiles of acalabrutinib and zanubrutinib in chronic lymphocytic leukemia: A real-world comparison2025 · 1 citations