Efficacy of Bruton tyrosine kinase inhibitors in mantle cell lymphoma with central nervous system involvement: a meta-analysis

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Background. Mantle cell lymphoma (MCL) is a highly aggressive disease characterized by rapid progression, with central nervous system (CNS) involvement reported in 1–4 % of cases, significantly worsening outcomes. Bruton tyrosine kinase (BTK) inhibitors have shown promising results in treating MCL; however, their efficacy in cases with CNS involvement (CNSi) remains controversial. This requires a systematic analysis of existing data to optimize therapeutic strategies. Aim. To evaluate the efficacy of BTK inhibitors in patients with CNSi of MCL. Materials and methods. A systematic search was conducted using the PubMed database, covering the period from January 1, 2013, to December 15, 2024. Inclusion criteria were as follows: morphologically confirmed MCL with CNSi, treatment with BTK inhibitors, and assessment of at least one therapeutic efficacy endpoint, including overall response rate, complete and partial response rates, overall survival, and hazard ratio estimates. Data analysis was performed in R (v4.4.2) using the meta package (v8.0–1). Combined metrics were calculated using fixed-­effects or random-­effects models, with 95 % confidence intervals (CIs) provided for all outcomes. Results. The meta-analysis summarized data from six retrospective studies involving 170 patients with MCL and CNS involvement. The use of BTK inhibitors was associated with a 74 % reduction in the risk of adverse outcomes (HR 0,26; 95 % CI: 0,13–0,52; p = 0.0001) compared to intrathecal and standard immunochemotherapy. Combined rates of complete and partial responses to BTK inhibitors were 41,8 % and 36,2 %, respectively, with minimal heterogeneity between studies. The overall response rate reached 74,95 %, demonstrating the stability of therapeutic efficacy. The absence of significant statistical heterogeneity ( I 2 ≤37,9 %) supports the robustness of these findings. Conclusions. Compared to intrathecal and standard immunochemotherapy, BTK inhibitors significantly improve response rates and reduce the risk of adverse outcomes in patients with MCL and CNSi. However, overall clinical outcomes remain suboptimal, underscoring the need for further research and the development of more effective treatment strategies.

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