High dose Methotrexate with intrathecal methotrexate? – pro
Because the CNS complications of NHL are relatively rare, there is limited prospective and/or randomized data to guide its therapy. Historically, CNS lymphomas have been associated with a very poor prognosis. On the other hand, an accumulation of recent prospective phase 1/2 results, as well as retrospective series, demonstrate reproducible improvements in outcomes for patients. These improvement are due to control within the CNS.
Importantly, Glantz and colleagues demonstrated that intravenous administration of methotrexate (8 g/m2 over 4 hours) produces higher cytotoxic levels of methotrexate (>1 M) in serum and CSF than intrathecal methotrexate (12-mg dose) at 48 and 72 hours. In addition, retrospective analysis of PCNSL outcomes at Memorial Sloan-Kettering Cancer Center demonstrated that the elimination of intrathecal methotrexate from induction therapy did not affect outcome in patients treated with HD-MTX at a target dose of 3.5 g/m. Rubenstein et al concluded that HD-MTX is sufficient to treat brain and leptomeningeal disease, withotu intrathecal methotrexate. Current guidelines suggest that prophylaxis may benefit DLBCL patients at high risk for CNS relapse.
Peñalver FJ, Sancho JM, de la Fuente A, et al. Guidelines for diagnosis, prevention and management of central nervous system involvement in diffuse large B-cell lymphoma patients by the Spanish Lymphoma Group (GELTAMO). Haematologica. 2017;102(2):235-245.
Kevin H. Hall, PharmDElyse Hall Panjic, PharmD, BCOPKelly Valla, PharmD, BCOPChristopher R. Flowers, MD, MSJonathon B. Cohen, MD, MSHow to Decide Which DLBCL Patients Should Receive CNS Prophylaxis, Oncology, 32(6), 2018
James L. Rubenstein, Neel K. Gupta, Gabriel N. Mannis, Amanda K. LaMarre and Patrick Treseler, How I treat CNS lymphomas. Blood 2013 122:2318-2330;
Hellmann M, Barnes JA, et al, . Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer 2010;116(18):4283-4290.
James L. Rubenstein, Neel K. Gupta, Gabriel N. Mannis, Amanda K. LaMarre and Patrick Treseler, How I treat CNS lymphomas. Blood 2013 122:2318-2330;
Glantz MJ, Cole BF, Recht L, et al
. High-dose intravenous methotrexate for patients with nonleukemic leptomeningeal cancer: is intrathecal chemotherapy necessary? J Clin Oncol 1998;16(4):1561-1567.
Hellmann M, Barnes JA, et al, . Intravenous methotrexate as central nervous system (CNS) prophylaxis is associated with a low risk of CNS recurrence in high-risk patients with diffuse large B-cell lymphoma. Cancer 2010;116(18):4283-4290.