Addition of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation in patients aged 65 years or younger with mantle cell lymphoma (MCL Younger): a randomised, open-label, phase 3 trial of the European Mantle Cell Lymphoma Network

被引：318

作者：

Hermine, Olivier ^{[1
,4
,5
]}

Hoster, Eva ^{[6
,7
]}

Walewski, Jan ^{[8
,9
]}

Bosly, Andre ^{[10
]}

Stilgenbauer, Stephan ^{[11
]}

Thieblemont, Catherine ^{[12
]}

Szymczyk, Michal ^{[8
,9
]}

Bouabdallah, Reda ^{[13
]}

Kneba, Michael ^{[14
]}

Hallek, Michael ^{[15
]}

Salles, Gilles ^{[16
]}

Feugier, Pierre ^{[17
]}

Ribrag, Vincent ^{[18
]}

Birkmann, Josef ^{[19
]}

Forstpointner, Roswitha ^{[6
]}

Haioun, Corinne ^{[20
]}

Haenel, Mathias ^{[21
]}

Casasnovas, Rene Olivier ^{[22
]}

Finke, Juergen ^{[23
]}

Peter, Norma ^{[24
]}

Bouabdallah, Kamal ^{[25
]}

Sebban, Catherine ^{[26
]}

Fischer, Thomas ^{[27
]}

Duehrsen, Ulrich ^{[28
]}

Metzner, Bernd ^{[29
]}

Maschmeyer, Georg ^{[30
]}

Kanz, Lothar ^{[31
]}

Schmidt, Christian ^{[6
]}

Delarue, Richard ^{[1
]}

Brousse, Nicole ^{[2
]}

Klapper, Wolfram ^{[32
,33
]}

Macintyre, Elizabeth ^{[3
]}

Delfau-Larue, Marie-Helene ^{[34
]}

Pott, Christiane ^{[14
]}

Hiddemann, Wolfgang ^{[6
]}

Unterhalt, Michael ^{[6
]}

Dreyling, Martin ^{[6
]}

机构：

[1] Univ Paris 05, Hop Necker, AP HP, Dept Hematol, Paris, France

[2] Univ Paris 05, Hop Necker, AP HP, Dept Pathol, Paris, France

[3] Univ Paris 05, Hop Necker, AP HP, Dept Biol Hematol, Paris, France

[4] Univ Sorbonne Paris Cite, INSERM U1163, Paris, France

[5] Univ Sorbonne Paris Cite, CNRS 8254, Imagine Inst, Paris, France

[6] Ludwig Maximilians Univ Hosp Munich, Dept Internal Med 3, D-81377 Munich, Germany

[7] Univ Munich, Inst Med Informat Biometry & Epidemiol, Munich, Germany

[8] Maria Skiodowska Curie Mem Canc Ctr, Dept Lymphoid Malignancies, Warsaw, Poland

[9] Inst Oncol, Warsaw, Poland

[10] Louvain Catholic Univ, Namur Univ Hosp, Namur, Belgium

[11] Univ Ulm, Dept Internal Med, Ulm, Germany

[12] St Louis Hosp, AP HP, Hematooncol Dept, Paris, France

[13] Inst Paoli Calmettes, Dept Hematol, Marseille, France

[14] Univ Hosp Schleswig Holstein, Dept Med 2, Kiel, Germany

[15] Univ Cologne, Dept Internal Med, Cologne, Germany

[16] Univ Claude Bernard, Ctr Hosp Lyon Sud, Hosp Civils Lyon, Pierre Benite, France

[17] Nancy Univ Hosp, Dept Hematol, Nancy, France

[18] Inst Gustave Roussy, Villejuif, France

[19] Paracelsus Med Univ, Dept Oncol, Nurnberg, Germany

[20] Hosp Henri Mondor, Lymphoid Malignancies Unit, Creteil, France

[21] Klinikum Chemnitz, Dept Internal Med 3, Chemnitz, Germany

[22] CHU Dijon, Hematol Clin, Dijon, France

[23] Univ Hosp Freiburg, Dept Hematol & Oncol, Freiburg, Germany

[24] Carl Thiem Klinikum Cottbus, Dept Med 2, Cottbus, Germany

[25] Univ Hosp Bordeaux, Dept Hematol & Cell Therapy, Pessac, France

[26] Ctr Leon Berard, Dept Haematol, Lyon, France

[27] Univ Hosp Magdeburg, Dept Hematol & Oncol, Magdeburg, Germany

[28] Univ Hosp Essen, Dept Hematol, Essen, Germany

[29] Univ Hosp Oldenburg, Dept Hematol & Oncol, Oldenburg, Germany

[30] Ernst von Bergmann Hospital, Dept Hematol Oncol & Palliat Med, Potsdam, Germany

[31] Univ Tubingen, Dept Med 2, Tubingen, Germany

[32] Univ Kiel, Hematopathol Sect, Dept Pathol, Kiel, Germany

[33] Univ Kiel, Lymph Node Registry, Kiel, Germany

[34] UPEC Univ, Dept Biol Hematol & Immunol, Henri Mondor Hosp, AP HP,INSERM U9SS, Creteil, France

来源：

LANCET | 2016年 / 388卷 / 10044期

关键词：

1ST-LINE TREATMENT; RESPONSE CRITERIA; PLUS RITUXIMAB; FREE SURVIVAL; FOLLOW-UP; THERAPY; CHOP; INDOLENT; TEMSIROLIMUS; MULTICENTER;

D O I：

10.1016/S0140-6736(16)00739-X

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Background Mantle cell lymphoma is characterised by a poor long-term prognosis. The European Mantle Cell Lymphoma Network aimed to investigate whether the introduction of high-dose cytarabine to immunochemotherapy before autologous stem-cell transplantation (ASCT) improves outcome. Methods This randomised, open-label, parallel-group, phase 3 trial was done in 128 haemato-oncological hospital departments or private practices in Germany, France, Belgium, and Poland. Patients aged 65 years or younger with untreated stage II IV mantle cell lymphoma were centrally randomised (1:1), with computer-assisted random block selection, to receive either six courses of R-CHOP (rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone) followed by myeloablative radiochemotherapy and AS CT (control group), or six courses of alternating R-CHOP or R-DHAP (rituximab plus dexamethasone, high-dose cytarabine, and cisplatin) followed by a high-dose cytarabine-containing conditioning regimen and AS CT (cytarabine group). Patients were stratified by study group and international prognostic index. The primary outcome was time to treatment failure from randomisation to stable disease after at least four induction cycles, progression, or death from any cause. Patients with stage II IV mantle cell lymphoma were included in the primary analysis if treatment was started according to randomisation. For safety analyses, patients were assessed according to the treatment actually started. This study is registered with ClinicalTrials.gov, number NCT00209222. Findings Of 497 patients (median age 55 years [IQR 49-60]) randomised from July 20,2004, to March 18,2010,234 of 249 in the control group and 232 of 248 in the cytarabine group were included in the primary analysis. After a median follow-up of 6.1 years (95% CI 5.4-6.4), time to treatment failure was significantly longer in the cytarabine group (median 9.1 years [95% CI 6.3 not reached], 5 year rate 65% [95% CI 57-71]) than in the control group (3 " 9 years [3.2-4 " 4], 40% [33-46]; hazard ratio 0.56; p=0.038). During induction immunochemotherapy, patients who received high-dose cytarabine had increased grade 3 or 4 haematological toxicity (haemoglobin 71 [29%] of 241 vs 19 [8%] of 227 controls; platelets 176 [73%] of 240 vs 21 [9%] of 225), grade 3 or 4 febrile neutropenia (39 [17%] of 230 vs 19 [8%] of 224), and grade 1 or 2 renal toxicity (creatinine 102 [43%] of 236 vs 22 [10%] of 224). The number of AS CT-related deaths was similar (eight [3.4%]) in both groups. Interpretation Immunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma.

引用

页码：565 / 575

页数：11

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