• Olivier Hermine, Eva Hoster, Jan Walewski, André Bosly, Stephan Stilgenbauer, Catherine Thieblemont, Michal Szymczyk, Reda Bouabdallah, Michael Kneba, Michael Hallek, Gilles Salles, Pierre Feugier, Vincent Ribrag, Josef Birkmann, Roswitha Forstpointner, Corinne Haioun, Mathias Hänel, René Olivier Casasnovas, Jürgen Finke, Norma Peter, Kamal Bouabdallah, Catherine Sebban, Thomas Fischer, Ulrich Dührsen, Bernd Metzner, Georg Maschmeyer, Lothar Kanz, Christian Schmidt, Richard Delarue, Nicole Brousse, Wolfram Klapper, Elizabeth Macintyre, Marie-Hélène Delfau-Larue, Christiane Pott, Wolfgang Hiddemann, Michael Unterhalt, Martin Dreyling, and European Mantle Cell Lymphoma Network.
• Department of Hematology, Hôpital Necker, Assistance Publique Hôpitaux de Paris, University Paris Descartes, Paris, France; INSERM U1163 and CNRS 8254, Imagine Institute, Université Sorbonne Paris Cité, Paris, France.
• Lancet. 2016 Aug 6; 388 (10044): 565-75.

BackgroundMantle 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.MethodsThis 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 ASCT (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 ASCT (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.FindingsOf 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 241m 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 ASCT-related deaths was similar (eight [3.4%]) in both groups.InterpretationImmunochemotherapy containing high-dose cytarabine followed by ASCT should be considered standard of care in patients aged 65 years or younger with mantle cell lymphoma.FundingEuropean Commission, Lymphoma Research Foundation, and Roche.Copyright © 2016 Elsevier Ltd. All rights reserved.

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