Dosage of high‐dose methotrexate as CNS prophylaxis in DLBCL: A detailed analysis of toxicity and impact on CNS relapse

Abstract

Central nervous system (CNS) relapse in diffuse large B-cell lymphoma (DLBCL) is a rare event, occurring in 2%-5% and is associated with a poor prognosis. 1 Certain patient and disease characteristics significantly increase this risk. 2 CNS-directed prophylaxis has often been incorporated into first-line therapy in patients at highest risk. In light of cumulative evidence suggesting that intrathecal (IT) therapy is ineffective, 3 high-dose intravenous methotrexate (HD-MTX) has become widely used as prophylaxis, based largely on retrospective, underpowered analyses suggesting a potential benefit. 4 We published an analysis of 1384 patients receiving HD-MTX prophylaxis either intercalated between R-CHOP (i-HD-MTX) or at "end-of-treatment" (EOT), demonstrating increased R-CHOP delays with i-HD-MTX and, crucially, similar rates of CNS relapse between the approaches. 5 EOT HD-MTX is now considered the optimal approach. The overall rate of CNS relapse seen in patients with a high CNS-IPI (9.1%), despite the use of HD-MTX, raised the question as to