Zanubrutinib showed a higher response rate than other BTK inhibitors in B-cell lymphomas

Brukinsa (zanubrutinib) showed higher complete and overall response rates than Calquence (acalabrutinib) and Imbruvica (ibrutinib) across B-cell lymphomas, suggesting it could be the most effective Bruton tyrosine kinase (BTK) inhibitor for these cancers, according to a study published on March 7 in Oncology and Therapy.

BTK inhibitors have become the foundation of treatment for many B-cell lymphomas, but evidence comparing the effectiveness of different drugs in this class has been limited, the study said. B-cell lymphomas account for approximately 85% to 90% of non-Hodgkin lymphoma cases, a group of blood cancers that affect B cells, T cells and natural killer cells.

The study said researchers estimate that approximately 80,350 people in the U.S. will be diagnosed with non-Hodgkin lymphoma in 2025, with approximately 19,390 deaths expected.

Over the past decade, BTK inhibitor monotherapies such as zanubrutinib, acalabrutinib and ibrutinib have improved outcomes for patients with several B-cell malignancies, including chronic lymphocytic leukemia (CLL), Waldenström macroglobulinemia, mantle cell lymphoma (MCL) and marginal zone lymphoma (MZL). Ibrutinib, the first BTK inhibitor approved, marked a major shift in treatment by improving survival compared with earlier therapies. Newer agents such as acalabrutinib and zanubrutinib were developed with greater selectivity, which could reduce off-target effects and improve tolerability while maintaining strong clinical activity.

Other research supports zanubrutinib’s effectiveness across B-cell cancers. A review of studies found that more than 80% of patients with either new or relapsed CLL responded to treatment. In patients with relapsed or refractory MCL, zanubrutinib also produced lasting responses and longer progression-free survival, showing it can help control the disease over time.

However, comparisons across all three therapies and multiple B-cell lymphoma indications have been limited, creating a need for further analyses to guide treatment decisions.

To address this gap, researchers conducted a meta-analysis comparing three BTK inhibitors across several types of B-cell lymphomas. The study was led by Pier Luigi Zinzani, of the University of Bologna in Italy, with collaborators from BeOne Medicines, Thermo Fisher Scientific and HB HEOR.

Using a systematic approach, the researchers reviewed and pooled data from previously published clinical trials evaluating BTK inhibitor monotherapy in patients with B-cell lymphomas. The analysis included zanubrutinib, acalabrutinib and ibrutinib, examining treatment response across both treatment-naive patients and those with relapsed or refractory disease. The cancers studied included CLL, Waldenström macroglobulinemia, MCL and MZL.

Because direct comparisons among all three drugs are limited, the meta-analysis used pooled data to evaluate outcomes such as complete response (CR) and overall response rates (ORRs), which will provide more comparative evidence for clinicians selecting therapies.

The study included 22 clinical trials with 3,599 patients across four B-cell lymphoma indications. Most of the trials (15 of 22) focused on relapsed or refractory disease, whereas four included treatment-naive patients and three assessed mixed populations. CLL accounted for the largest share of studies at 42%. Researchers examined both CR and ORR, and pooled analyses showed significant improvements with zanubrutinib.

Data revealed that across indications, the odds of achieving a CR were 1.80 times higher than acalabrutinib and 2.85 times higher than ibrutinib. In relapsed or refractory MCL, zanubrutinib’s advantage was more pronounced, with odds of CR 3.33 times higher than acalabrutinib and 9.53 times higher than ibrutinib. In relapsed or refractory MZL, zanubrutinib achieved superior CR rates compared with ibrutinib.

ORR showed similar trends, with zanubrutinib outperforming both comparators in most indications. Statistical heterogeneity was moderate to high, but results consistently favored zanubrutinib, reinforcing its potential as a leading BTK inhibitor for B-cell lymphomas.

The study also showed both the strengths and limits of the results and methods of the overall study. Strengths include the large number of trials and patients, which gives a broad view of how the drugs compare. Limitations include relying on single-arm studies, differences across trials and variation in patient and disease characteristics, which could make the results less generalized.

The authors note that response rates alone don’t show long-term outcomes, including progression-free or overall survival. They suggest future studies to confirm these findings, look at factors affecting treatment response and fully assess safety.