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/m2 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/m2 vs.3.5 g/m2, 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/m2 provided a higher CR rate and PFS benefits with acceptable adverse effects.