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