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

被引：71

作者：

Wilson, Matthew R. ^{[1
]}

Eyre, Toby A. ^{[2
]}

Kirkwood, Amy A. ^{[3
,4
]}

Doo, Nicole Wong ^{[5
]}

Soussain, Carole ^{[6
]}

Choquet, Sylvain ^{[7
]}

Martinez-Calle, Nicolas ^{[8
]}

Preston, Gavin ^{[9
]}

Ahearne, Matthew ^{[10
]}

Schorb, Elisabeth ^{[11
]}

Moles-Moreau, Marie-Pierre ^{[12
]}

Ku, Matthew ^{[13
]}

Rusconi, Chiara ^{[14
]}

Khwaja, Jahanzaib ^{[15
]}

Narkhede, Mayur ^{[16
]}

Lewis, Katharine L. ^{[17
,18
]}

Calimeri, Teresa ^{[19
]}

Durot, Eric ^{[20
]}

Renaud, Loic ^{[21
]}

Ovlisen, Andreas Kiesbye ^{[22
]}

McIlroy, Graham ^{[23
]}

Ebsworth, Timothy J. ^{[24
]}

Elliot, Johnathan ^{[25
]}

Santarsieri, Anna ^{[26
]}

Ricard, Laure ^{[27
]}

Shah, Nimish ^{[28
]}

Liu, Qin ^{[29
]}

Zayac, Adam S. ^{[30
,31
]}

Vassallo, Francesco ^{[32
]}

Lebras, Laure ^{[33
]}

Roulin, Louise ^{[34
]}

Lombion, Naelle ^{[35
]}

Manos, Kate ^{[36
]}

Fernandez, Ruben ^{[37
]}

Hamad, Nada ^{[38
]}

Lopez-Garcia, Alberto ^{[39
]}

O'Mahony, Deirdre ^{[40
]}

Gounder, Praveen ^{[5
]}

Forgeard, Nathalie ^{[7
]}

Lees, Charlotte ^{[2
]}

Agbetiafa, Kossi ^{[6
]}

Struessmann, Tim ^{[11
]}

Htut, Thura Win ^{[9
]}

Clavert, Aline ^{[12
]}

Scott, Hamish ^{[13
]}

Guidetti, Anna ^{[14
]}

Barlow, Brett R. ^{[16
]}

Tchernonog, Emmanuelle ^{[41
]}

Smith, Jeffery ^{[42
]}

Miall, Fiona ^{[10
]}

机构：

[1] Beatson West Scotland Canc Ctr, Glasgow, Lanark, Scotland

[2] Oxford Univ Hosp NHS Trust, Churchill Canc Ctr, Oxford, England

[3] UCL Canc Inst, Canc Res UK, London, England

[4] UCL Canc Inst, UCL Canc Trials Ctr, London, England

[5] Concord Hosp Univ Sydney, Concord Clin Sch, Sydney, NSW, Australia

[6] Inst Curie Hop Rene Huguenin, St Cloud, France

[7] Sorbonne Univ, La Pitie Salpetriere Hosp, Assistance Publ Hop Paris AP HP, Paris, France

[8] Nottingham Univ Hosp NHS Trust, Nottingham, England

[9] Aberdeen Royal Infirm, Aberdeen, Scotland

[10] Univ Hosp Leicester NHS Trust, Leicester, Leics, England

[11] Univ Med Ctr Freiburg, Dept Med, Freiburg, Germany

[12] CHU Angers, Serv Malad Sang, Angers, France

[13] St Vincents Private Hosp Melbourne, Melbourne, Vic, Australia

[14] Fdn IRCCS Ist Nazl Tumori, Milan, Italy

[15] Univ Coll London Hosp NHS Fdn Trust, London, England

[16] Univ Alabama Birmingham, Birmingham, AL USA

[17] Linear Clin Res, Perth, WA, Australia

[18] Sir Charles Gairdner Hosp, Perth, WA, Australia

[19] IRCCS San Raffaele Sci Inst, Milan, Italy

[20] CHU Reims, Hop Robert Debre, Reims, France

[21] Hop St Louis, AP HP, Paris, France

[22] Aalborg Univ Hosp, Aalborg, Denmark

[23] Univ Hosp Birmingham, Birmingham, W Midlands, England

[24] Univ Hosp Southampton NHS Fdn Trust, Southampton, Hants, England

[25] Christie NHS Fdn Trust, Manchester, Lancs, England

[26] Cambridge Univ Hosp NHS Fdn Trust, Cambridge, England

[27] Hosp St Antoine, AP HP, Paris, France

[28] Norfolk & Norwich Univ Hosp NHS Fdn Trust, Norwich, Norfolk, England

[29] Princess Margaret Canc Ctr, Toronto, ON, Canada

[30] Brown Univ, Providence, RI 02912 USA

[31] Lifespan Canc Inst, Providence, RI USA

[32] Citta Salute & Sci Torino, Turin, Italy

[33] Ctr Leon Berard, Lyon, France

[34] Univ Hosp Henri Mondor, AP HP, Paris, France

[35] Ctr Hosp Versailles, Hop Mignot, Versailles, France

[36] Austin Hosp, Melbourne, Vic, Australia

[37] Hosp Cabuenes, Gijon, Spain

[38] St Vincents Hosp Sydney, Sydney, NSW, Australia

[39] Fdn Jimenez Diaz Univ Hosp, Hlth Res Inst, Inst Invest Sanitaria, Fdn Jimenex Diaz IIS FJD, Madrid, Spain

[40] Bon Secours Cork Canc Ctr, Cork, Ireland

[41] CHU Montpellier, Montpellier, France

[42] Liverpool Univ Hosp Fdn Trust, Liverpool, Merseyside, England

来源：

BLOOD | 2022年 / 139卷 / 16期

关键词：

B-CELL LYMPHOMA; NERVOUS-SYSTEM RELAPSE; HIGH-RISK PATIENTS; SINGLE-ARM; OPEN-LABEL; PHASE-III; R-CHOP; RITUXIMAB; LENALIDOMIDE; STRATEGIES;

D O I：

10.1182/blood.2021014506

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

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 5 749) or at the end (n 5 635) 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 5.98; 3-year difference: 0.04% (22.0% to 3.1%). Conclusions were unchanged on adjusting for baseline prognostic factors or on 6-month landmark analysis (n 5 1253). In patients with a high CNS international prognostic index (n 5 600), 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.

引用

页码：2499 / 2511

页数：13

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