CNS Prophylaxis in High-Risk Diffuse Large B-Cell Lymphoma

Prophylactic high-dose methotrexate (MTX), intrathecal MTX, or both are commonly given in conjunction with induction immunochemotherapy for patients with diffuse large B-cell lymphoma (DLBCL) and risk factors for parenchymal or leptomeningeal central nervous system (CNS) relapse; risk factors include testicular, sinonasal, renal, and adrenal sites of disease. To determine whether timing of MTX administration affects outcomes, investigators conducted an international retrospective analysis of 1384 patients with newly diagnosed DLBCL who were deemed at high risk for CNS relapse.

Patients had received cycles of induction R-CHOP or R-CHOP-like regimens (rituximab, cyclophosphamide, hydroxydaunorubicin, vincristine, and prednisone) along with high-dose MTX administered either intercalated with or after completion of the induction cycles. Roughly half of patients also received intrathecal MTX.

The 3-year rate of CNS relapse did not differ between the intercalated-MTX and end-of-treatment-MTX groups (5.7% and 5.8%). In the subset of patients with the highest CNS-international prognostic index risk scores, relapse rates also were similar in the two groups (9.1% and 10.5%, respectively). Intrathecal MTX did not affect outcomes. Treatment-related toxicities were higher with intercalated MTX, which impaired the ability to deliver on-schedule, full-dose induction therapy — which may in turn impair systemic disease control.