Efficacy and Safety of BTKis in Central Nervous System Lymphoma: A Systematic Review and Meta-Analysis

Simple Summary Central nervous system lymphoma (CNSL) is a highly aggressive form of lymphoma. However, treatments such as chemotherapy and radiotherapy may be intolerable for older or specific patients due to the associated toxicity and severe neurotoxicity. Some studies have shown that Bruton tyrosine kinase inhibitors (BTKis) are effective for CNSL. However, most of these studies were small-sample studies, so the efficacy and safety of BTKis in CNSL are not yet clearly defined. Furthermore, the existing reviews have mainly focused on patients with relapsed/refractory CNSL or primary CNSL, and there have been fewer studies on second-generation BTKis, with a lack of reviews on the evidence of BTKis for CNSL. Therefore, this systematic review aims to comprehensively and systematically elucidate the efficacy and safety of BTKis in the treatment of CNSL. The results indicate that BTKis are effective not only for relapsed/refractory cases but also for newly diagnosed CNSL, with an acceptable safety profile. However, high-quality clinical trials are still needed in the future.Abstract Background: This systematic review and meta-analysis aimed to evaluate the efficacy and safety of Bruton tyrosine kinase inhibitors (BTKis) for central nervous system lymphoma (CNSL). Methods: A systematic review was carried out to identify relevant studies from the PubMed, Embase, Cochrane Library, Web of Science, WanFang, CNKI, and CBM databases. The studies included patients with CNSL who received BTKis and reported the overall response (OR), complete remission (CR), and partial response (PR). An overall effect analysis was performed using STATA 15.0. A random-effects model was utilized to calculate the pooled rates, and 95% confidence intervals (CI) were determined for all outcomes. Results: A total of 21 studies involving 368 patients were included in the meta-analysis. For newly diagnosed CNSL, due to the small simple size, we conducted a quantitative description, and the ORR could reach up to 100%. For relapsed/refractory patients, the pooled ORR was 72% (95% CI: 64-80%, I2 = 54.89%, p = 0.00), with a pooled CR and PR of 43% (95% CI: 33-54%, I2 = 65.40%, p = 0.00) and 23% (95% CI: 13-35%, I2 = 78.05%, p = 0.00), respectively. Most adverse events were hematology-related and generally manageable. Conclusion: BTKis showed acceptable efficacy and safety in treating patients with CNSL. However, large and well-designed trials are still required to confirm BTKis as a treatment for CNSL.