Efficacy and safety of ibrutinib in central nervous system lymphoma: A systematic review and meta-analysis.

Background: Primary central nervous system lymphoma (CNSL) is a rare, aggressive non-Hodgkin lymphoma confined to the CNS. Although radiation and chemotherapy, particularly high-dose methotrexate (HD-MTX), are effective treatments, the relapse rates remain high, prompting the exploration of novel therapeutic options. Ibrutinib, an irreversible Bruton tyrosine kinase (BTK) inhibitor, has shown promise in various B-cell malignancies, including CNSL.

Objectives: This systematic review and meta-analysis aimed to evaluate the safety and efficacy of ibrutinib in the treatment of CNSL, focusing on overall response (OR), complete response (CR), partial response (PR), progression-free survival (PFS), overall survival (OS), and adverse events.

Methods: A comprehensive search of the PubMed, Google Scholar, and Scopus databases was conducted. The included studies were prospective and retrospective studies focusing on ibrutinib as monotherapy or in combination with CNSL. Data extraction and quality assessment were independently performed by two reviewers, and statistical analyses were conducted using R version 4.4.0.

Results: Fourteen studies (eight cohort studies and six clinical trials) involving 784 patients were included. The median age was 61 years, with nearly equal sex distribution. The meta-analysis for CNSL, the partial response rate was 29.52 %, complete response rate was 49.19 %, and overall response rate was 72.11 %. For PCNSL, the partial response rate was 20.85 %, complete response rate was 48.13 %, and overall response rate was 66.92 %. For SCNSL, the partial response rate was 29.42 %, complete response rate was 44.64 %, and overall response rate was 66.82 %. Significant heterogeneity was observed in some comparisons. There were no significant differences in the efficacy of ibrutinib between CNSL subtypes.

Conclusions: Ibrutinib shows promising efficacy in improving partial and complete response rates in CNSL. The substantial heterogeneity observed underscores the need for further well-designed studies to confirm these findings and explore the optimal use of ibrutinib in CNSL treatment protocols. Future trials should consider comparing ibrutinib to standard therapies and investigate its long-term efficacy and safety profile.