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

作者：Matthew R. Wilson, Amy A. Kirkwood, Nicole Wong Doo, Carole Soussain, Sylvain Choquet, Charlotte Lees, Christopher P. Fox, Gavin Preston, Matthew J. Ahearne, Tim Strüßmann, Aline Clavert, Chiara Rusconi, Matthew Ku, Jahanzaib Khwaja, Mayur Narkhede, Katharine L. Lewis, Éric Durot, Jeffery Smith, Loïc Renaud, Andrés J.M. Ferreri, Tarec Christoffer El‐Galaly, Kate Cwynarski, Pam McKay, Toby A. Eyre · 发表于：American Journal of Hematology · 年份：2023 · DOI：10.1002/ajh.27167 · 被引用次数：6 · 研究领域：CNS Lymphoma Diagnosis and Treatment、Lymphoma Diagnosis and Treatment、Glioma Diagnosis and Treatment

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 whether it has any benefit, irrespective of delivery time. Several additional studies have addressed this question,6-9 with the largest being a recent retrospective analysis of 2418 patients.10 There was no clinically significant reduction in CNS relapse in patients in first complete remission who received HD-MTX (n = 356), nor any clear benefit in ultra-high risk subgroups. Accepting the limitations of retrospective analyses, there is now sig...