Originally published as JCO Early Release 10.1200/JCO.2005.08.133 on January 24 2005
Journal of Clinical Oncology, Vol 23, No 9 (March 20), 2005: pp. 1984-1992
© 2005 American Society of Clinical Oncology.
Immunochemotherapy With Rituximab and Cyclophosphamide, Doxorubicin, Vincristine, and Prednisone Significantly Improves Response and Time to Treatment Failure, But Not Long-Term Outcome in Patients With Previously Untreated Mantle Cell Lymphoma: Results of a Prospective Randomized Trial of the German Low Grade Lymphoma Study Group (GLSG)
Georg Lenz,
Martin Dreyling,
Eva Hoster,
Bernhard Wörmann,
Ulrich Dührsen,
Bernd Metzner,
Hartmut Eimermacher,
Andreas Neubauer,
Hannes Wandt,
Hjalmar Steinhauer,
Sonja Martin,
Else Heidemann,
Ali Aldaoud,
Reza Parwaresch,
Joerg Hasford,
Michael Unterhalt,
Wolfgang Hiddemann
From the Department of Internal Medicine III, Ludwig-Maximilians University; Department of Medical Informatics, Biometrics and Epidemiology (IBE), Ludwig-Maximilians University, Munich; Department of Internal Medicine II, Städtisches Klinikum Braunschweig, Braunschweig; Department of Hematology, University of Essen, Essen; Department of Internal Medicine II, Klinikum Oldenburg, Oldenburg; Department of Hematology and Oncology, Katholisches Krankenhaus, Hagen, Hagen; Department of Hematology and Oncology, University of Marburg, Marburg; Department of Hematology and Oncology, Klinikum Nord, Nuernberg; Department of Internal Medicine II, Carl-Thiem Klinikum, Cottbus; Department of Internal Medicine II, Robert-Bosch-Hospital; Department of Internal Medicine II, Diakonie-Klinikum, Stuttgart; Praxis für Hämatologie/Onkologie, Leipzig; Department of Hematopathology and Lymph Node Registry Kiel, Kiel, Germany
Address reprint requests to Wolfgang Hiddemann, MD, PhD, Department of Internal Medicine III of the Ludwig-Maximilians University, Marchioninistrasse 15, 81377 Munich, Germany; e-mail: wolfgang.hiddemann{at}med.uni-muenchen.de
PURPOSE: Mantle cell lymphoma (MCL) is characterized by a poor prognosis with a low to moderate sensitivity to chemotherapy and a median survival of only 3 to 4 years. In an attempt to improve outcome, the German Low Grade Lymphoma Study Group (GLSG) initiated a randomized trial comparing the combination of cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) and rituximab (R-CHOP) with CHOP alone as first-line therapy for advanced-stage MCL.
PATIENTS AND METHODS: One hundred twenty-two previously untreated patients with advanced-stage MCL were randomly assigned to six cycles of CHOP (n = 60) or R-CHOP (n = 62). Patients up to 65 years of age achieving a partial or complete remission underwent a second randomization to either myeloablative radiochemotherapy followed by autologous stem-cell transplantation or interferon alfa maintenance (IFN ). All patients older than 65 years received IFN maintenance.
RESULTS: R-CHOP was significantly superior to CHOP in terms of overall response rate (94% v 75%; P = .0054), complete remission rate (34% v 7%; P = .00024), and time to treatment failure (TTF; median, 21 v 14 months; P = .0131). No differences were observed for progression-free survival. Toxicity was acceptable, with no major differences between the two therapeutic groups.
CONCLUSION: The combined immunochemotherapy with R-CHOP resulted in a significantly higher response rate and a prolongation of the TTF as compared with chemotherapy alone. Hence, R-CHOP may serve as a new baseline regimen for advanced stage MCL, but needs to be further improved by novel strategies in remission.
Supported in part by a grant from the Deutsche Krebshilfe (T14/96/Hi 1, project No.: 70-2208-Hi 2).
Presented in part at the 40th Annual Meeting of the American Society of Clinical Oncology, New Orleans, LA, June 5-8, 2004.
Authors' disclosures of potential conflicts of interest are found at the end of this article.
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B. D. Cheson and J. P. Leonard
Monoclonal Antibody Therapy for B-Cell Non-Hodgkin's Lymphoma
N. Engl. J. Med.,
August 7, 2008;
359(6):
613 - 626.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Tarella, M. Zanni, M. Magni, F. Benedetti, C. Patti, T. Barbui, A. Pileri, M. Boccadoro, F. Ciceri, A. Gallamini, et al.
Rituximab Improves the Efficacy of High-Dose Chemotherapy With Autograft for High-Risk Follicular and Diffuse Large B-Cell Lymphoma: A Multicenter Gruppo Italiano Terapie Innnovative nei Linfomi Survey
J. Clin. Oncol.,
July 1, 2008;
26(19):
3166 - 3175.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Martin, A. Chadburn, P. Christos, R. Furman, J. Ruan, M. A. Joyce, E. Fusco, P. Glynn, R. Elstrom, R. Niesvizky, et al.
Intensive treatment strategies may not provide superior outcomes in mantle cell lymphoma: overall survival exceeding 7 years with standard therapies
Ann. Onc.,
July 1, 2008;
19(7):
1327 - 1330.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Bottcher, M. Ritgen, S. Buske, S. Gesk, W. Klapper, E. Hoster, W. Hiddemann, M. Unterhalt, M. Dreyling, R. Siebert, et al.
Minimal residual disease detection in mantle cell lymphoma: methods and significance of four-color flow cytometry compared to consensus IGH-polymerase chain reaction at initial staging and for follow-up examinations
Haematologica,
April 1, 2008;
93(4):
551 - 559.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
O. Determann, E. Hoster, G. Ott, H. Wolfram Bernd, C. Loddenkemper, M. Leo Hansmann, T. E. F. Barth, M. Unterhalt, W. Hiddemann, M. Dreyling, et al.
Ki-67 predicts outcome in advanced-stage mantle cell lymphoma patients treated with anti-CD20 immunochemotherapy: results from randomized trials of the European MCL Network and the German Low Grade Lymphoma Study Group
Blood,
February 15, 2008;
111(4):
2385 - 2387.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
F. Morschhauser, J. F. Seymour, H. C. Kluin-Nelemans, A. Grigg, M. Wolf, M. Pfreundschuh, H. Tilly, J. Raemaekers, M. B. van 't Veer, N. Milpied, et al.
A phase II study of enzastaurin, a protein kinase C beta inhibitor, in patients with relapsed or refractory mantle cell lymphoma
Ann. Onc.,
February 1, 2008;
19(2):
247 - 253.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
E. Hoster, M. Dreyling, W. Klapper, C. Gisselbrecht, A. van Hoof, H. C. Kluin-Nelemans, M. Pfreundschuh, M. Reiser, B. Metzner, H. Einsele, et al.
A new prognostic index (MIPI) for patients with advanced-stage mantle cell lymphoma
Blood,
January 15, 2008;
111(2):
558 - 565.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. S. Kahl
New Therapeutic Strategies for Mantle Cell Lymphoma
ASCO Educational Book,
January 1, 2008;
2008(1):
392 - 397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
D. J. Straus
How I Treat Mantle Cell Lymphoma
J. Oncol. Pract,
September 1, 2007;
3(5):
281 - 282.
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Thieblemont and B. Coiffier
Lymphoma in Older Patients
J. Clin. Oncol.,
May 10, 2007;
25(14):
1916 - 1923.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
H. Schulz, J. F. Bohlius, S. Trelle, N. Skoetz, M. Reiser, T. Kober, G. Schwarzer, M. Herold, M. Dreyling, M. Hallek, et al.
Immunochemotherapy With Rituximab and Overall Survival in Patients With Indolent or Mantle Cell Lymphoma: A Systematic Review and Meta-analysis
J Natl Cancer Inst,
May 2, 2007;
99(9):
706 - 714.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Watanabe, N. Homma, N. Ogata, H. Saito, T. Kanefuji, K. Hasegawa, K. Soga, K. Shibasaki, T. Endo, and Y. Ajioka
Complete response in a patient with colonic mantle cell lymphoma with multiple lymphomatous polyposis treated with combination chemotherapy using anti-CD20 antibody and cladribine
Gut,
March 1, 2007;
56(3):
449 - 450.
[Full Text]
[PDF]
|
|
|
|
|
|
|
P. Dreger, M. Rieger, B. Seyfarth, M. Hensel, M. Kneba, A. D. Ho, N. Schmitz, and C. Pott
Rituximab-augmented myeloablation for first-line autologous stem cell transplantation for mantle cell lymphoma: effects on molecular response and clinical outcome
Haematologica,
January 1, 2007;
92(1):
42 - 49.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Bello and E. M. Sotomayor
Monoclonal Antibodies for B-Cell Lymphomas: Rituximab and Beyond
Hematology,
January 1, 2007;
2007(1):
233 - 242.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Forstpointner, M. Unterhalt, M. Dreyling, H.-P. Bock, R. Repp, H. Wandt, C. Pott, J. F. Seymour, B. Metzner, A. Hanel, et al.
Maintenance therapy with rituximab leads to a significant prolongation of response duration after salvage therapy with a combination of rituximab, fludarabine, cyclophosphamide, and mitoxantrone (R-FCM) in patients with recurring and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low Grade Lymphoma Study Group (GLSG)
Blood,
December 15, 2006;
108(13):
4003 - 4008.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Fisher, S. H. Bernstein, B. S. Kahl, B. Djulbegovic, M. J. Robertson, S. de Vos, E. Epner, A. Krishnan, J. P. Leonard, S. Lonial, et al.
Multicenter Phase II Study of Bortezomib in Patients With Relapsed or Refractory Mantle Cell Lymphoma
J. Clin. Oncol.,
October 20, 2006;
24(30):
4867 - 4874.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. F. Leahy, J. F. Seymour, R. J. Hicks, and J. H. Turner
Multicenter Phase II Clinical Study of Iodine-131-Rituximab Radioimmunotherapy in Relapsed or Refractory Indolent Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
September 20, 2006;
24(27):
4418 - 4425.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. Kahl, W. Longo, J. Eickhoff, J Zehnder, C Jones, J Blank, T McFarland, W Bottner, H Rezazedeh, J Werndli, et al.
Maintenance rituximab following induction chemoimmunotherapy may prolong progression-free survival in mantle cell lymphoma: a pilot study from the Wisconsin Oncology Network
Ann. Onc.,
September 1, 2006;
17(9):
1418 - 1423.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
C. Pott, C. Schrader, S. Gesk, L. Harder, M. Tiemann, T. Raff, M. Bruggemann, M. Ritgen, B. Gahn, M. Unterhalt, et al.
Quantitative assessment of molecular remission after high-dose therapy with autologous stem cell transplantation predicts long-term remission in mantle cell lymphoma
Blood,
March 15, 2006;
107(6):
2271 - 2278.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
I. F. Khouri
Reduced-Intensity Regimens in Allogeneic Stem-Cell Transplantation for Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
Hematology,
January 1, 2006;
2006(1):
390 - 397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. F. Israel, M. Gulley, S. Elmore, S. Ferrini, W.-h. Feng, and S. C. Kenney
Anti-CD70 antibodies: a potential treatment for EBV+ CD70-expressing lymphomas
Mol. Cancer Ther.,
December 1, 2005;
4(12):
2037 - 2044.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. R. Klumpp
R-CHOP for Mantle Cell Lymphoma
J. Clin. Oncol.,
September 20, 2005;
23(27):
6802 - 6802.
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Hiddemann, G. Lenz, M. Dreyling, and M. Unterhalt
In Reply:
J. Clin. Oncol.,
September 20, 2005;
23(27):
6802 - 6803.
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. E. Witzig
Current Treatment Approaches for Mantle-Cell Lymphoma
J. Clin. Oncol.,
September 10, 2005;
23(26):
6409 - 6414.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
T. Kober, N. Skoetz, S. Trelle, J. Bohlius, and A. Engert
Third Biannual Report of the Cochrane Haematological Malignancies Group
J Natl Cancer Inst,
August 17, 2005;
97(16):
E2 - E.
[Full Text]
|
|
|
|
|
|
|
M. J. Rummel, S. E. Al-Batran, S.-Z. Kim, M. Welslau, R. Hecker, D. Kofahl-Krause, K.-M. Josten, H. Durk, A. Rost, M. Neise, et al.
Bendamustine Plus Rituximab Is Effective and Has a Favorable Toxicity Profile in the Treatment of Mantle Cell and Low-Grade Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
May 20, 2005;
23(15):
3383 - 3389.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Dreyling, G. Lenz, E. Hoster, A. Van Hoof, C. Gisselbrecht, R. Schmits, B. Metzner, L. Truemper, M. Reiser, H. Steinhauer, et al.
Early consolidation by myeloablative radiochemotherapy followed by autologous stem cell transplantation in first remission significantly prolongs progression-free survival in mantle-cell lymphoma: results of a prospective randomized trial of the European MCL Network
Blood,
April 1, 2005;
105(7):
2677 - 2684.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Ghielmini
Multimodality Therapies and Optimal Schedule of Antibodies: Rituximab in Lymphoma as an Example
Hematology,
January 1, 2005;
2005(1):
321 - 328.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
