Comparative Efficacy of BTK Inhibitors in Treatment-Naïve and Relapsed/Refractory Mantle Cell Lymphoma: A Systematic Review and Meta-Analysis.

Bruton tyrosine kinase inhibitors (BTKis) have been employed in the treatment of mantle cell lymphoma (MCL). However, direct comparisons of ibrutinib, zanubrutinib, and acalabrutinib across treatment-naïve (TN) and relapsed/refractory (R/R) MCL remain limited. This meta-analysis was intended to evaluate their efficacy, addressing critical gaps in clinical decision-making. We systematically searched PubMed, Embase, and Cochrane up to January 2025 for studies (RCT/single-arm) assessing the efficacy of BTKis in MCL patients. Among 70 studies, the pooled CR rate in the TN group was higher than that in the R/R group (76.5% vs. 43.2%). Among TN patients, the CR rate of the regimen incorporating zanubrutinib (95.2% [95% CI 0.893, 1.000]) was significantly higher than that of the regimens containing acalabrutinib or ibrutinib (p = 0.0042). In the R/R group, the BTKi + anti-CD20 monoclonal antibody + small-molecular therapy group presented a better CR rate (68.3% [95% CI 0.546, 0.820]; p < 0.0001). When comparing the monotherapy efficacy of three BTKis in R/R MCL, the results indicated that acalabrutinib exhibited a higher CR rate (43.2% [95% CI 0.339, 0.525]) than zanubrutinib or ibrutinib. In addition, zanubrutinib-based therapy exhibited a lower pooled rate of haematological toxicities compared to the other two BTKi therapies. This work resolved critical uncertainties in BTKi selection for MCL, demonstrating acalabrutinib's and zanubrutinib's first-line potential, leading to a meaningful improvement in response rate and a manageable safety profile. Chemotherapy-free regimen can partially overcome the traditionally unfavourable prognosis associated with R/R MCL. These results provide a roadmap for optimizing MCL therapy. Chemotherapy-free regimens for MCL based on BTKis warrant further validation in RCTs. These findings may advocate for updated guidelines prioritizing zanubrutinib and acalabrutinib in clinical practice.