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News|Articles|March 10, 2026

Zanubrutinib Leads Other BTK Inhibitors Across B-Cell Lymphomas in Meta-Analysis

Author(s)Mary Caffrey
Fact checked by: Skylar Jeremias
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Key Takeaways

  • A two-step approach pooled indication-specific response rates, then generated naïve odds ratios via random-effects models, reflecting limited head-to-head evidence across BTK inhibitors.
  • Across indications, zanubrutinib improved CR versus acalabrutinib (OR 1.80) and ibrutinib (OR 2.85), and improved ORR versus acalabrutinib (OR 1.59) and ibrutinib (OR 2.25).
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Meta-analysis across B-cell lymphomas shows zanubrutinib (Brukinsa) delivers higher ORR/CR than acalabrutinib (Calquence) or ibrutinib among BTK inhibitors.

Treatment with zanubrutinib (Brukinsa; BeOne Medicines) was linked to more improved overall response (ORR) and complete response (CR) rates compared with acalabrutinib (Calquence; AstraZeneca) and ibrutinib (Imbruvica; Janssen) across multiple B-cell lymphoma indications, according to a meta-analysis published this week in Oncology and Therapy.1

The study, led by Pier Luigi Zinzani, MD, PhD, of the University of Bologna, was funded by BeOne Medicines. The authors wrote that their analysis aimed to address the lack of direct comparisons across the 3 FDA-approved Bruton tyrosine kinase (BTK) inhibitors—zanubrutinib, acalabrutinib, and ibrutinib—which are widely used in treating B-cell malignancies, both as monotherapy and in combination with other agents.

This meta-analysis compared the efficacy of these 3 agents across 4 indications: chronic lymphocytic leukemia (CLL), mantle cell lymphoma (MCL), marginal zone lymphoma (MZL), and Waldenström macroglobulinemia (WM), at both the treatment-naïve (TN) and relapsed/refractory (R/R) stages.

They noted that the ELEVATE-RR trial, which involved patients with R/R CLL,2 did show that acalabrutinib had similar efficacy compared with ibrutinib. But otherwise, there are few data sets for clinicians to use to directly compare therapies.

“Given the variety of available treatments for B cell lymphoma and scarcity of head-to-head comparative evidence, there is a data gap and unmet need for evidence that evaluates the relative response of zanubrutinib, ibrutinib, and acalabrutinib across various B cell lymphoma indications,” the authors wrote.

The researchers drew on 22 clinical trials encompassing 3599 patients. Because most data came from single-arm rather than head-to-head trials, the team used a 2-step statistical approach: pooling response rates within each indication, then performing a meta-analysis to produce naïve odds ratios (ORs) across each indication, using a random effects model.

Across all indications, the pooled OR for CR was 1.80 (95% CI, 1.03-3.13), favoring zanubrutinib over acalabrutinib, and 2.85 (95% CI, 1.16-7.04), favoring zanubrutinib over ibrutinib. For ORR, pooled ORs were 1.59 (95% CI, 1.00-2.53) and 2.25 (95% CI, 1.40-3.61) against acalabrutinib and ibrutinib, respectively.

Results in R/R mantle cell lymphoma were among the most striking. Zanubrutinib demonstrated statistically superior CR compared with both acalabrutinib (OR 3.33; 95% CI, 1.91-5.81) and ibrutinib (OR 9.53; 95% CI, 5.45-16.66). Zanubrutinib also showed significantly better ORR versus ibrutinib in R/R MCL (OR 2.23; 95% CI, 1.21-4.12). In R/R MZL, zanubrutinib outperformed ibrutinib on both CR (OR 3.32) and ORR (OR 2.39). In TN CLL, zanubrutinib showed higher ORR than both comparators and higher CR versus acalabrutinib.

The authors noted that these findings are consistent with existing head-to-head trial data, including the ALPINE trial3 in R/R CLL and the ASPEN trial4 in WM. Taken together, the data suggest that zanubrutinib is the most effective BTK inhibitor treatment option for patients across B-cell lymphomas.

“To our knowledge, no other head-to-head trials exist comparing zanubrutinib, acalabrutinib, and ibrutinib in patients with CLL, MCL, MZL, or WM,” they wrote. “The findings of this study provide insights into the comparative response rates associated with these BTK [inhibitors] and suggest that zanubrutinib may offer an effective—if not more effective—treatment option for patients with B cell lymphoma.”

There are several limitations. Among other issues, reliance on single-arm trial data introduces potential confounding, and no formal risk-of-bias assessment was conducted. In addition, the study was sponsored by the manufacturer of zanubrutinib, with several authors employed by BeOne Medicines.

References

  1. Zinzani PL, Williams R, Xue M, et al. A meta-analysis investigating response rates with continuous Bruton tyrosine kinase inhibitor monotherapies in the treatment of B cell lymphomas. Oncol Ther. Published online March 7, 2026. doi: 10.1007/s40487-026-00425-y
  2. Byrd JC, Hillmen P, Ghia P, et al. Acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia: results of the first randomized phase III trial. J Clin Oncol. 2021;39(31):3441-3452. doi:10.1200/JCO.21.01210
  3. Brown JR, Eichhorst B, Lamanna N, et al. Sustained benefit of zanubrutinib vs ibrutinib in patients with R/R CLL/SLL: final comparative analysis of ALPINE. Blood. 2024;144(26):2706-2717. doi:10.1182/blood.2024024667
  4. Tam CS, Opat S, D'Sa S, et al. A randomized phase 3 trial of zanubrutinib vs ibrutinib in symptomatic Waldenström macroglobulinemia: the ASPEN study. Blood;136(18):2038-2050. doi:10.1182/blood.2020006844

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