High-dose methotrexate dosing strategy in primary central nervous system lymphoma
Alexander Wang1, Frank Cirrone1, Francis Andrew De Los Reyes1
1Department of Pharmacy, NYU Langone Health, New York, NY, USA.
Leukemia & Lymphoma
|February 5, 2022
Summary
Lower doses of high-dose methotrexate (HD-MTX) for primary CNS lymphoma (PCNSL) show comparable efficacy with reduced toxicity. This approach may improve treatment completion, especially for vulnerable patients.
Area of Science:
- Oncology
- Neurology
- Pharmacology
Background:
- Primary central nervous system lymphoma (PCNSL) treatment relies on high-dose methotrexate (HD-MTX) and rituximab.
- The optimal HD-MTX dosage for PCNSL induction therapy is not definitively established, with varying effective doses reported.
Purpose of the Study:
- To evaluate the efficacy and safety of a reduced HD-MTX dose (3-5 g/m²) in PCNSL induction therapy.
- To compare outcomes of lower-dose HD-MTX with higher doses in PCNSL patients.
Main Methods:
- Retrospective analysis of PCNSL patients receiving HD-MTX at 3-5 g/m².
- Assessment of overall response rate, complete response, overall survival, and progression-free survival.
- Documentation of adverse events, including nephrotoxicity and hepatotoxicity.
Main Results:
- An overall response rate of 81.8% was observed, with 50% achieving complete response.
- Median overall survival was not reached at 29 months; median progression-free survival was 12.5 months.
- Hepatotoxicity occurred in 18.5% of patients; two discontinuations were due to nephrotoxicity, with no treatment-related mortality.
Conclusions:
- HD-MTX at 3-5 g/m² demonstrates comparable efficacy to higher doses in PCNSL, with a potentially better safety profile.
- Lowering the initial HD-MTX dose may enhance treatment tolerability and completion rates, particularly in elderly patients or those with comorbidities.
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