Efficacy and safety of rituximab in the treatment of primary central nervous system lymphoma: A meta-analysis and systematic review of 1,388 patients.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive form of non-Hodgkin's lymphoma with a generally poor prognosis, and the median age at diagnosis is 65 years. The clinical value of rituximab in the treatment of PCNSL remains controversial. The present study aimed to evaluate the therapeutic benefits and safety of rituximab in patients with newly diagnosed PCNSL. The EMBASE, PubMed, Web of Science and Cochrane Library were systematically searched from database inception to May 5, 2025, without any language restrictions. Efficacy outcomes included complete remission (CR), overall survival (OS) and progression-free survival (PFS). Safety outcomes were assessed by adverse drug reactions. Statistical analysis was performed using Review Manager 5.3 and Stata16 software to calculate relative risks and 95% confidence intervals (CIs) for categorical data and to analyze survival data. The meta-analysis included 15 studies with 1,388 patients, with a relatively high proportion of males and elderly individuals, and comparable baseline characteristics between rituximab-containing chemotherapy group and the standard chemotherapy-alone control group. Compared with the control group, the rituximab combination group achieved a significantly improved 3-year OS, with an odds ratio (OR) of 2.01 (95% CI: 1.42-2.84, P<0.00001). The combined hazard ratio (HR) for OS was 0.57 (95% CI: 0.36-0.91, P=0.02). The 3-year PFS also showed significant improvement in the rituximab group with an OR of 2.3 (95% CI: 1.47-3.58, P=0.0002), and the combined PFS-HR was 0.54 (95% CI: 0.37-0.79, P=0.002). The rate of CR was significantly higher with an OR of 2.04 (95% CI: 1.5-2.77, P<0.00001). For safety outcomes, the OR for grade ≥3 leukopenia was 1.74 (95% CI: 0.92-3.27, P=0.09) and the OR for any-grade hepatic toxicity was 1.42 (95% CI: 0.98-2.05, P=0.06). In subgroup analyses, the OR for 3-year OS was 2.62 (95% CI: 1.16-5.91) for Asians and 1.69 (95% CI: 1.23-2.32) for Caucasians; the OR for 3-year PFS was 2.98 (95% CI: 1.17-7.6) for Asians and 2.02 (95% CI: 1.22-3.34) for Caucasians. In conclusion, based on this meta-analysis, rituximab significantly improved the prognosis of patients with PCNSL without a significant difference in safety compared to the existing treatment regimens. Further high-quality randomized controlled trials are warranted to confirm these findings.