Therapeutic Impact of Zanubrutinib in Chronic Lymphocytic Leukemia: Evidence from a Systematic Review and Single-Arm...

Background and Objective: Zanubrutinib, a next-generation Bruton's tyrosine kinase inhibitor (BTKi), has demonstrated promising efficacy in chronic lymphocytic leukemia (CLL), including treatment-naïve (TN) and relapsed/refractory (R/R) patients. However, evidence synthesis across clinical trials remains limited. We conducted a systematic review and single-arm meta-analysis to evaluate the efficacy of zanubrutinib in CLL. Methods: This study was performed in accordance with PRISMA guidelines and Cochrane recommendations. PubMed, Medline, Scopus, and Web of Science were searched up to August 2025 using terms related to zanubrutinib and CLL/SLL. Eligible studies included clinical trials of zanubrutinib in TN or R/R CLL/SLL patients. Risk of bias was assessed using the JBI tool for non-randomized studies and for RCTs. Pooled estimates of efficacy outcomes were calculated using a random-effects model. Pooled estimates were calculated using the DerSimonian-Laird random-effects model, which accounts for both within- and between-study variability. Results: Seven studies (n > 1000) were included, enrolling both TN and R/R patients across diverse global populations. The pooled overall response rate (ORR) was 93.3% (95% CI, 86.7-99.8%) in mixed TN and R/R populations, 94.4% (95% CI, 91.6-97.3%) in TN patients, and 83.9% (95% CI, 75.0-92.8%) in R/R patients. Complete response (CR) rates were 12.2% (95% CI, 0.3-24.2%) overall, 13.8% (95% CI, 1.5-26.2%) in TN patients, and 5.0% (95% CI, 0.3-9.8%) in R/R patients. Partial response (PR) rates reached 86.0% (95% CI, 82.6-89.5%) in TN and 63.2% (95% CI, 53.5-73.0%) in R/R patients. Progressive disease was rare (≤1% in R/R cohorts). Heterogeneity was moderate to high across several outcomes. Conclusions: Zanubrutinib demonstrates favorable efficacy in CLL, achieving high ORR in both TN and R/R patients, with particularly durable responses in TN populations. Although complete response rates remain modest, especially among R/R patients, overall disease control appears consistent. These findings support zanubrutinib as an effective treatment option across CLL settings; however, variability among studies and the modest CR rates highlight the need for longer follow-up and direct comparative trials to further define its clinical role.