Comparison of high dose methotrexate treatments in CNS lymphoma patients: The Henry Ford experience.
Selim R, Philip J, and Donthireddy V. Comparison of high dose methotrexate treatments in CNS lymphoma patients: The Henry Ford experience. J Clin Oncol 2017; 35(15)
J Clin Oncol
Background: The main backbone of therapy for CNS lymphoma involves systemic treatment with high dose methotrexate (HDMTX)-based regimens, with radiotherapy reserved only for cases that fail systemic therapy due to the significant cognitive toxicity of radiation. Over the last decade, rituximab and subsequently temozolomide were added to HDMTX chemotherapy regimens. Methods: Patients diagnosed with CNS lymphoma between 2009 and 2015 were identified. A retrospective cohort study was conducted of patients who received HDMTX alone (Cohort A), HDMTX and rituximab (Cohort B) and HDMTX, rituximab and temozolomide (Cohort C). Data collected included treatment related adverse events along with OS and PFS. Results: 31 patients were diagnosed with CNS lymphoma. 11, 10 and 6 patients were in cohorts A, B and C respectively. Median PFS and OS for the entire cohort were 14 and 25 months respectively. Cohort results were compared to the respective reference trials published in the literature. Cohort A had a PFS of 11 months and OS of 12 months compared to 12.8 months and 22.8+ months in the reference Phase II trial. Cohort B had a median PFS of 25+ months and OS of 41 months compared to 21 months and 33.5 months in the reference trial. Cohort C had a 2-year PFS of 0.50 compared to 0.57 in the reference trial. 3 (9.6%), 5 (16.1%), and 2 (6.4%) patients developed renal dysfunction in cohorts A, B and C respectively. 4 (12.9), 2 (6.4%), and 0 patients developed leukopenia in cohorts A, B and C respectively. 3 (9.6), 2 (6.4%), and 1 (3.2%) patients developed anemia in cohorts A, B and C respectively. 1 (3.2%), 1 (3.2%) and 1 (3.2%) patient developed thrombocytopenia in cohorts A, B and C respectively. Conclusions: The addition of Rituximab to HDMTX treatment for the treatment of CNS lymphoma increased the PFS and OS compared to HDMTX alone and is in concordance with the reference phase II trials reported in the literature if not better. In addition, our data at HFH shows no increased risk of adverse events with combination therapies compared to HDMTX alone. The addition of Temozolomide to Rituximab and High Dose methotrexate treatment showed a median 2 year PFS of 0.50 which is comparable to published reports of a 2-year PFS of 0.59.