Alternating R-CHOP and R-cytarabine is a safe and effective regimen for transplant-ineligible patients with a newly diagnosed mantle cell lymphoma

被引:17
作者
Klener, Pavel [1 ,2 ]
Fronkova, Eva [3 ,4 ]
Belada, David [5 ,6 ]
Forsterova, Kristina [1 ]
Pytlik, Robert [1 ]
Kalinova, Marketa [7 ,8 ]
Simkovic, Martin [5 ,6 ]
Salek, David [9 ]
Mocikova, Heidi [10 ,11 ]
Prochazka, Vit [12 ,13 ]
Blahovcova, Petra [1 ]
Janikova, Andrea [9 ]
Markova, Jana [10 ,11 ]
Obr, Ales [12 ,13 ]
Berkova, Adela [14 ]
Kubinyi, Jozef [15 ]
Vaskova, Martina [3 ,4 ]
Mejstrikova, Ester [3 ,4 ]
Campr, Vit [7 ,8 ]
Jaksa, Radek [16 ]
Kodet, Roman [7 ,8 ]
Michalova, Kyra [14 ]
Trka, Jan [3 ,4 ]
Trneny, Marek [1 ]
机构
[1] Charles Univ Prague, Gen Hosp Prague, Med Dept 1, Prague, Czech Republic
[2] Charles Univ Prague, Inst Pathol Physiol, Fac Med 1, Prague, Czech Republic
[3] Second Fac Med, Deparment Pediat Hematol Oncol, CLIP, Prague, Czech Republic
[4] Univ Hosp Motol, Prague, Czech Republic
[5] Charles Univ Hosp Hradec Kralove, Dept Internal Med Hematol 4, Hradec Kralove, Czech Republic
[6] Fac Med Hradec Kralove, Hradec Kralove, Czech Republic
[7] Charles Univ Hosp Motol, Dept Pathol & Mol Med, Prague, Czech Republic
[8] Second Fac Med, Prague, Czech Republic
[9] Masaryk Univ Hosp Brno, Dept Hematol & Oncol, Brno, Czech Republic
[10] Charles Univ Prague, Fac Hosp Kralovske Vinohrady, Dept Internal Med & Haematol, Prague, Czech Republic
[11] Charles Univ Prague, Fac Med 3, Dept Internal Med & Haematol, Prague, Czech Republic
[12] Palacky Univ, Fac Med & Dent, Dept Hematooncol, Olomouc, Czech Republic
[13] Univ Hosp Olomouc, Olomouc, Czech Republic
[14] Charles Univ Prague, Fac Med 1, Inst Clin Biochem & Lab Diagnost, Ctr Oncocytogenet, Prague, Czech Republic
[15] Charles Univ Prague, Gen Hosp Prague, Inst Nucl Med, Prague, Czech Republic
[16] Charles Univ Prague, Inst Pathol, Gen Hosp Prague, Prague, Czech Republic
关键词
elderly patients; high-dose cytarabine; mantle cell lymphoma; PET-CT; rituximab maintenance; DOSE CYTARABINE; PLUS RITUXIMAB; OPEN-LABEL; MULTICENTER; TRIAL; IMMUNOCHEMOTHERAPY; BENDAMUSTINE; THERAPY;
D O I
10.1002/hon.2483
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Implementation of cytarabine into induction therapy became standard of care for younger patients with mantle cell lymphoma (MCL). On the basis of its beneficial impact, many centers incorporated cytarabine at lower doses also into first-line treatments of elderly patients. We conducted a multicenter observational study that prospectively analyzed safety and efficacy of alternating 3+3cycles of R-CHOP and R-cytarabine for newly diagnosed transplant-ineligible MCL patients. A total of 73 patients were enrolled with median age 70years. Most patients had intermediate (39.7%) and high-risk (50.7%) disease according to MCL international prognostic index. Rituximab maintenance was initiated in 58 patients. Overall response rate reached 89% by positron emission tomography-computed tomography, including 75.3% complete remissions. Two patients (2.7%) did not complete the induction therapy because of toxicity. Three patients (4.1%) were considered nonresponders, which led to therapy change before completion of induction. Estimated progression-free survival and overall survival were 51.3% and 68.6% at 4years, respectively. Mantle cell lymphoma international prognostic index, bulky disease ( 5cm), and achievement of positron emission tomography-negativity independently correlated with progression-free survival. Grade 3 to 4 hematologic and nonhematologic toxicity was documented in 48% and 20.5% patients, respectively. Alternation of R-CHOP and R-cytarabine represents feasible and very effective regimen for elderly/comorbid MCL patients. This study was registered at GovTrial () NCT03054883.
引用
收藏
页码:110 / 115
页数:6
相关论文
共 10 条
[1]   Revised response criteria for malignant lymphoma [J].
Cheson, Bruce D. ;
Pfistner, Beate ;
Juweid, Malik E. ;
Gascoyne, Randy D. ;
Specht, Lena ;
Horning, Sandra J. ;
Coiffier, Bertrand ;
Fisher, Richard I. ;
Hagenbeek, Anton ;
Zucca, Emanuele ;
Rosen, Steven T. ;
Stroobants, Sigrid ;
Lister, T. Andrew ;
Hoppe, Richard T. ;
Dreyling, Martin ;
Tobinai, Kensei ;
Vose, Julie M. ;
Connors, Joseph M. ;
Federico, Massimo ;
Diehl, Volker .
JOURNAL OF CLINICAL ONCOLOGY, 2007, 25 (05) :579-586
[2]   Newly diagnosed and relapsed mantle cell lymphoma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up [J].
Dreyling, M. ;
Geisler, C. ;
Hermine, O. ;
Kluin-Nelemans, H. C. ;
Le Gouill, S. ;
Rule, S. ;
Shpilberg, O. ;
Walewski, J. ;
Ladetto, M. .
ANNALS OF ONCOLOGY, 2014, 25 :83-92
[3]   Long-term progression-free survival of mantle cell lymphoma after intensive front-line immunochemotherapy with in vivo-purged stem cell rescue:: a nonrandomized phase 2 multicenter study by the Nordic Lymphoma Group [J].
Geisler, Christian H. ;
Kolstad, Arne ;
Laurell, Anna ;
Andersen, Niels S. ;
Pedersen, Lone B. ;
Jerkeman, Mats ;
Eriksson, Mikael ;
Nordstrom, Marie ;
Kimby, Eva ;
Boesen, Anne Marie ;
Kuittinen, Outi ;
Lauritzsen, Grete F. ;
Nilsson-Ehle, Herman ;
Ralfkiaer, Elisabeth ;
Akerman, Mans ;
Ehinger, Mats ;
Sundstrom, Christer ;
Langholm, Ruth ;
Delabie, Jan ;
Karjalainen-Lindsberg, Marja-Liisa ;
Brown, Peter ;
Elonen, Erkki .
BLOOD, 2008, 112 (07) :2687-2693
[4]   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 [J].
Hermine, Olivier ;
Hoster, Eva ;
Walewski, Jan ;
Bosly, Andre ;
Stilgenbauer, Stephan ;
Thieblemont, Catherine ;
Szymczyk, Michal ;
Bouabdallah, Reda ;
Kneba, Michael ;
Hallek, Michael ;
Salles, Gilles ;
Feugier, Pierre ;
Ribrag, Vincent ;
Birkmann, Josef ;
Forstpointner, Roswitha ;
Haioun, Corinne ;
Haenel, Mathias ;
Casasnovas, Rene Olivier ;
Finke, Juergen ;
Peter, Norma ;
Bouabdallah, Kamal ;
Sebban, Catherine ;
Fischer, Thomas ;
Duehrsen, Ulrich ;
Metzner, Bernd ;
Maschmeyer, Georg ;
Kanz, Lothar ;
Schmidt, Christian ;
Delarue, Richard ;
Brousse, Nicole ;
Klapper, Wolfram ;
Macintyre, Elizabeth ;
Delfau-Larue, Marie-Helene ;
Pott, Christiane ;
Hiddemann, Wolfgang ;
Unterhalt, Michael ;
Dreyling, Martin .
LANCET, 2016, 388 (10044) :565-575
[5]   Treatment of Older Patients with Mantle-Cell Lymphoma [J].
Kluin-Nelemans, H. C. ;
Hoster, E. ;
Hermine, O. ;
Walewski, J. ;
Trneny, M. ;
Geisler, C. H. ;
Stilgenbauer, S. ;
Thieblemont, C. ;
Vehling-Kaiser, U. ;
Doorduijn, J. K. ;
Coiffier, B. ;
Forstpointner, R. ;
Tilly, H. ;
Kanz, L. ;
Feugier, P. ;
Szymczyk, M. ;
Hallek, M. ;
Kremers, S. ;
Lepeu, G. ;
Sanhes, L. ;
Zijlstra, J. M. ;
Bouabdallah, R. ;
Lugtenburg, P. J. ;
Macro, M. ;
Pfreundschuh, M. ;
Prochazka, V. ;
Di Raimondo, F. ;
Ribrag, V. ;
Uppenkamp, M. ;
Andre, M. ;
Klapper, W. ;
Hiddemann, W. ;
Unterhalt, M. ;
Dreyling, M. H. .
NEW ENGLAND JOURNAL OF MEDICINE, 2012, 367 (06) :520-531
[6]   Bortezomib-Based Therapy for Newly Diagnosed Mantle-Cell Lymphoma [J].
Robak, Tadeusz ;
Huang, Huiqiang ;
Jin, Jie ;
Zhu, Jun ;
Liu, Ting ;
Samoilova, Olga ;
Pylypenko, Halyna ;
Verhoef, Gregor ;
Siritanaratkul, Noppadol ;
Osmanov, Evgenii ;
Alexeeva, Julia ;
Pereira, Juliana ;
Drach, Johannes ;
Mayer, Jiri ;
Hong, Xiaonan ;
Okamoto, Rumiko ;
Pei, Lixia ;
Rooney, Brendan ;
van de Velde, Helgi ;
Cavalli, Franco .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 372 (10) :944-953
[7]   Lenalidomide plus Rituximab as Initial Treatment for Mantle-Cell Lymphoma [J].
Ruan, Jia ;
Martin, Peter ;
Shah, Bijal ;
Schuster, Stephen J. ;
Smith, Sonali M. ;
Furman, Richard R. ;
Christos, Paul ;
Rodriguez, Amelyn ;
Svoboda, Jakub ;
Lewis, Jessica ;
Katz, Orel ;
Coleman, Morton ;
Leonard, John P. .
NEW ENGLAND JOURNAL OF MEDICINE, 2015, 373 (19) :1835-1844
[8]   Bendamustine plus rituximab versus CHOP plus rituximab as first-line treatment for patients with indolent and mantle-cell lymphomas: an open-label, multicentre, randomised, phase 3 non-inferiority trial [J].
Rummel, Mathias J. ;
Niederle, Norbert ;
Maschmeyer, Georg ;
Banat, G. Andre ;
von Gruenhagen, Ulrich ;
Losem, Christoph ;
Kofahl-Krause, Dorothea ;
Heil, Gerhard ;
Welslau, Manfred ;
Balser, Christina ;
Kaiser, Ulrich ;
Weidmann, Eckhart ;
Duerk, Heinz ;
Ballo, Harald ;
Stauch, Martina ;
Roller, Fritz ;
Barth, Juergen ;
Hoelzer, Dieter ;
Hinke, Axel ;
Brugger, Wolfram .
LANCET, 2013, 381 (9873) :1203-1210
[9]   Rituximab, bendamustine, and low-dose cytarabine as induction therapy in elderly patients with mantle cell lymphoma: a multicentre, phase 2 trial from Fondazione Italiana Linfomi [J].
Visco, Carlo ;
Chiappella, Annalisa ;
Nassi, Luca ;
Patti, Caterina ;
Ferrero, Simone ;
Barbero, Daniela ;
Evangelista, Andrea ;
Spina, Michele ;
Molinari, Annalia ;
Rigacci, Luigi ;
Tani, Monica ;
Di Rocco, Alice ;
Pinotti, Graziella ;
Fabbri, Alberto ;
Zambello, Renato ;
Finotto, Silvia ;
Gotti, Manuel ;
Carella, Angelo M. ;
Salvi, Flavia ;
Pileri, Stefano A. ;
Ladetto, Marco ;
Ciccone, Giovannino ;
Gaidano, Gianluca ;
Ruggeri, Marco ;
Martelli, Maurizio ;
Vitolo, Umberto .
LANCET HAEMATOLOGY, 2017, 4 (01) :E15-E23
[10]   Mantle cell lymphoma: 2015 update on diagnosis, risk-stratification, and clinical management [J].
Vose, Julie M. .
AMERICAN JOURNAL OF HEMATOLOGY, 2015, 90 (08) :739-745