Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients

Wilson, Matthew R.; Eyre, Toby A.; Kirkwood, Amy A.; Wong Doo, Nicole; Soussain, Carole; Choquet, Sylvain; Martinez-Calle, Nicolás; Preston, Gavin; Ahearne, Matthew; Schorb, Elisabeth; Moles-Moreau, Marie-Pierre; Ku, Matthew; Rusconi, Chiara; Khwaja, Jahanzaib; Narkhede, Mayur; Lewis, Katharine L.; Calimeri, Teresa; Durot, Eric; Renaud, Loïc; Øvlisen, Andreas Kiesbye; McIlroy, Graham; Ebsworth, Timothy J.; Elliot, Johnathan; Santarsieri, Anna; Ricard, Laure; Shah, Nimish; Liu, Qin; Zayac, Adam S.; Vassallo, Francesco; Lebras, Laure; Roulin, Louise; Lombion, Naelle; Manos, Kate; Fernandez, Ruben; Hamad, Nada; Lopez-Garcia, Alberto; O'Mahony, Deirdre; Gounder, Praveen; Forgeard, Nathalie; Lees, Charlotte; Agbetiafa, Kossi; Strüßmann, Tim; Htut, Thura Win; Clavert, Aline; Scott, Hamish; Guidetti, Anna; Barlow, Brett R.; Tchernonog, Emmanuelle; Smith, Jeffery; Miall, Fiona; Fox, Christopher P.; Cheah, Chan Y.; El Galaly, Tarec Christoffer; Ferreri, Andrés J. M.; Cwynarski, Kate; McKay, Pam...

Abstract

Prophylactic high-dose methotrexate (HD-MTX) is often used for diffuse large B-cell lymphoma (DLBCL) patients at high risk of central nervous system (CNS) relapse, despite limited evidence demonstrating efficacy or the optimal delivery method. We conducted a retrospective, international analysis of 1384 patients receiving HD-MTX CNS prophylaxis either intercalated (i-HD-MTX) (n = 749) or at the end (n = 635) of R-CHOP/R-CHOP-like therapy (EOT). There were 78 CNS relapses (3-year rate 5.7%), with no difference between i-HD-MTX and EOT: 5.7% vs 5.8%, P =.98; 3-year difference: 0.04% (−2.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n = 1253). In patients with a high CNS international prognostic index (n = 600), the 3-year CNS relapse rate was 9.1%, with no difference between i-HD-MTX and EOT. On multivariable analysis, increasing age and renal/adrenal involvement were the only independent risk factors for CNS relapse. Concurrent intrathecal prophylaxis was not associated with a reduction in CNS relapse. R-CHOP delays of ≥7 days were significantly increased with i-HD-MTX vs EOT, with 308 of 1573 (19.6%) i-HD-MTX treatments resulting in a delay to subsequent R-CHOP (median 8 days). Increased risk of delay occurred in older patients when delivery was later than day 10 in the R-CHOP cycle. In summary, we found no evidence that EOT delivery increases CNS relapse risk vs i-HD-MTX. Findings in high-risk subgroups were unchanged. Rates of CNS relapse in this HD-MTX-treated cohort were similar to comparable cohorts receiving infrequent CNS prophylaxis. If HD-MTX is still considered for certain high-risk patients, delivery could be deferred until R-CHOP completion.

Citation

Wilson, M. R., Eyre, T. A., Kirkwood, A. A., Wong Doo, N., Soussain, C., Choquet, S., …McKay, P. (2022). Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients. Blood, 139(16), 2499-2511. https://doi.org/10.1182/blood.2021014506

• Journal Article Type: Article
• Acceptance Date: Dec 30, 2021
• Online Publication Date: Jan 11, 2022
• Publication Date: Apr 21, 2022
• Deposit Date: Feb 8, 2023
• Publicly Available Date: Feb 9, 2023
• Journal: Blood
• Print ISSN: 0006-4971
• Electronic ISSN: 1528-0020
• Publisher: American Society of Hematology
• Peer Reviewed: Peer Reviewed
• Volume: 139
• Issue: 16
• Pages: 2499-2511
• DOI: https://doi.org/10.1182/blood.2021014506
• Keywords: Cell Biology; Hematology; Immunology; Biochemistry
• Public URL: https://nottingham-repository.worktribe.com/output/17078441
• Publisher URL: https://ashpublications.org/blood/article-abstract/139/16/2499/483371/Timing-of-high-dose-methotrexate-CNS-prophylaxis?redirectedFrom=fulltext
• Additional Information: This research was originally published in Blood. Matthew R. Wilson et al. Title. Blood. 2022;139(16): 2499–2511. © the American Society of Hematology.