Improvement of outcomes of an escalated high-dose methotrexate-based regimen for patients with newly diagnosed primary central nervous system lymphoma: a real-world cohort study

Purpose: High-dose methotrexate (HD-MTX)-based chemotherapy regimen is the first-line treatment of primary central nervous system lymphoma (PCNSL). At present, doses of MTX in the range of 3.5-8 g/m(2) are frequently used. However, the optimal dose of methotrexate for PCNSL remains controversial. The purpose of this real-world study was to compare the efficacy and toxicity of HD-MTX in patients with untreated PCNSL. Methods: Immunocompetent adults with newly diagnosed PCNSL between January 2015 and December 2018 were investigated and followed up to June 2019. All patients' initial treatments were based on HD-MTX chemotherapy regimens. Results: A total of 73 patients were reviewed. For patients who received HD-MTX at 8 g/m(2) vs.3.5 g/m(2), the complete response (CR) rates were 68.29% vs 43.75% (p = 0.03), and the median PFS times were 17.7 months vs 9.05 months (HR=0.455, 95% CI 0.239-0.865, p=0.016). There was no significant difference in OS between the two groups. Serious adverse effects were uncommon and clinically manageable. Conclusion: There is a correlation of treatment response and clinical outcomes between the dosage of MTX in initial induction therapy in newly diagnosed PCNSL. MTX dose of 8 g/m(2) provided a higher CR rate and PFS benefits with acceptable adverse effects.