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Title: Timing of high-dose methotrexate CNS prophylaxis in DLBCL: a multicenter international analysis of 1384 patients.
Austin Authors: 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, Pamela
Affiliation: Austin Health
Beatson West of Scotland Cancer Centre, Glasgow, United Kingdom
Concord Clinical School, Concord Hospital University of Sydney, Sydney, NSW, Australia
St Vincent's Private Hospital Melbourne, Melbourne, VIC, Australia
St Vincent's Hospital Sydney, Sydney, Australia
Oxford University Hospitals NHS Trust, Churchill Cancer Center, Oxford, United Kingdom
Cancer Research UK and UCL Cancer Trials Centre, UCL Cancer Institute, London, United Kingdom
Institut Curie Hôpital René Huguenin, Saint-Cloud, France
La Pitie Salpetriere Hospital, Assistance Publique-Hôpitaux de Paris (AP-HP)-Sorbonne Universite, Paris, France
Nottingham University Hospitals NHS Trust, Nottingham, United Kingdom
Department of Medicine, University Medical Center Freiburg, Freiburg, Germany
Service des Maladies du Sang, CHU Angers, Angers, France
Fondazione IRCCS Istituto Nazionale dei Tumori, Milan, Italy
University of Alabama at Birmingham, Birmingham, AL
IRCCS San Raffaele Scientific Institute, Milan, Italy
Hôpital Robert Debré CHU de Reims, Reims, France
Hôpital Saint-Louis, AP-HP, Paris, France
University Hospitals Birmingham, Birmingham, United Kingdom
University Hospital Southampton NHS Foundation Trust, Southampton, United Kingdom
The Christie NHS Foundation Trust, Manchester, United Kingdom
Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom
Hospital Saint-Antoine AP-HP, Paris, France
Norfolk and Norwich University Hospitals NHS Foundation Trust, Norwich, United Kingdom
Princess Margaret Cancer Centre, Toronto, ON, Canada
Brown University and Lifespan Cancer Institute, Providence, RI
Città della Salute e della Scienza di Torino, Torino, Italy
Centre Léon Bérard, Lyon, France
University Hospital Henri-Mondor AP-HP, Paris, France
Hopital Mignot Centre Hospitalier de Versailles, Versailles, France
Hospital de Cabueñes, Gijon, Spain
Fundacion Jimenez Diaz University Hospital, Health Research Institute Instituto de Investigaciòn Sanitaria-Fundacion Jimenex Diaz (IIS-FJD), Madrid, Spain
Bon Secours Cork Cancer Centre, Cork, Ireland
Aberdeen Royal Infirmary, Aberdeen, United Kingdom
CHU de Montpellier, Montpellier, France
Liverpool University Hospitals Foundation Trust, Liverpool, United Kingdom
University Hospitals of Leicester NHS Trust, Leicester, United Kingdom
Aalborg University Hospital, Aalborg, Denmark
University College London Hospitals NHS Foundation Trust, London, United Kingdom
Linear Clinical Research and Sir Charles Gairdner Hospital, Perth, WA, Australia
Issue Date: 21-Apr-2022
Publication information: Blood 2022; 139(16): 2499-2511
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.
DOI: 10.1182/blood.2021014506
ORCID: 0000-0001-5423-3270
Journal: Blood
PubMed URL: 34995350
PubMed URL:
Type: Journal Article
Appears in Collections:Journal articles

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