Journal of Clinical Oncology, Vol 20, Issue 5
(March), 2002: 1288-1294
© 2002 American Society for Clinical Oncology
Rituximab and CHOP Induction Therapy for Newly Diagnosed Mantle-Cell Lymphoma: Molecular Complete Responses Are Not Predictive of Progression-Free Survival
By Orion M. Howard,
John G. Gribben,
Donna S. Neuberg,
Michael Grossbard,
Christina Poor,
Milos J. Janicek,
Margaret A. Shipp
From the Departments of Adult Oncology, Biostatistics, and Radiology, Dana-Farber Cancer Institute, and Division of Medical Oncology, Massachusetts General Hospital, Harvard Medical School, Boston, MA.
Address reprint requests to M. Shipp, MD, Dana-Farber Cancer Institute, 44 Binney St, Boston, MA 02115; email: margaret_shipp{at}dfci.harvard.edu
PURPOSE: To evaluate the efficacy of rituximab and cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) induction therapy in patients with newly diagnosed mantle-cell lymphoma (MCL).
PATIENTS AND METHODS: From March 1997 to May 1999, 40 previously untreated patients with stage II through IV MCL were treated with six cycles of rituximab and CHOP chemotherapy in a phase II trial. Pretreatment and interval peripheral-blood (PB) and bone marrow (BM) specimens were also analyzed by polymerase chain reaction (PCR) for tumor-specific BCL-1/immunoglobulin H (IgH) translocations and clonal IgH rearrangements. Study end points included clinical and molecular response rates and long-term progression-free survival (PFS).
RESULTS: Forty-eight percent of patients achieved a complete response (CR)/CR unconfirmed (CRu), and 48% of patients obtained a partial response (PR). However, 28 of the 40 patients have already relapsed or developed progressive disease with a median PFS of 16.6 months. Twenty-five patients had PCR-detectable BCL-1/IgH or clonal IgH products in PB or BM at diagnosis. Nine of the 25 informative patients had no evidence of PCR-detectable disease in PB or BM after rituximab and CHOP therapy. However, patients who achieved molecular remissions in PB or BM had PFS similar to patients without molecular remissions (16.5 v 18.8 months, P = .51).
CONCLUSION: Favorable clinical and molecular response rates associated with rituximab and CHOP chemotherapy do not translate into prolonged PFS in MCL. Nevertheless, rituximab and combination chemotherapy may transiently clear PB or BM of detectable tumor cells, prompting additional consideration of antibody-based in vivo purging in subsequent clinical trials.
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113(18):
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|
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|
|
|
|
|
|
|
C. H. Geisler, A. Kolstad, A. Laurell, N. S. Andersen, L. B. Pedersen, M. Jerkeman, M. Eriksson, M. Nordstrom, E. Kimby, A. M. Boesen, et al.
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112(7):
2687 - 2693.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. G. Till, M. C. Jensen, J. Wang, E. Y. Chen, B. L. Wood, H. A. Greisman, X. Qian, S. E. James, A. Raubitschek, S. J. Forman, et al.
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112(6):
2261 - 2271.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
B. D. Cheson and J. P. Leonard
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359(6):
613 - 626.
[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
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93(4):
551 - 559.
[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]
|
|
|
|
|
|
|
B. S. Kahl
New Therapeutic Strategies for Mantle Cell Lymphoma
ASCO Educational Book,
January 1, 2008;
2008(1):
392 - 397.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
X. Zhao, R. Lapalombella, T. Joshi, C. Cheney, A. Gowda, M. S. Hayden-Ledbetter, P. R. Baum, T. S. Lin, D. Jarjoura, A. Lehman, et al.
Targeting CD37-positive lymphoid malignancies with a novel engineered small modular immunopharmaceutical
Blood,
October 1, 2007;
110(7):
2569 - 2577.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
S. Nomura, K. Ishii, Y. Kamitsuji, N. Uoshima, E. Ishikawa, H. Kitayama, and K. Hayashi
Elevation of Activated Platelet-Dependent Chemokines in Patients With Anti-CD20 Monoclonal Antibody (Rituximab)-Treated Non-Hodgkin's Lymphoma
Clinical and Applied Thrombosis/Hemostasis,
April 1, 2007;
13(2):
206 - 212.
[Abstract]
[PDF]
|
|
|
|
|
|
|
F Morschhauser, S Depil, E Jourdan, M Wetterwald, R Bouabdallah, G Marit, P Solal-Celigny, C Sebban, B Coiffier, N Chouaki, et al.
Phase II study of gemcitabine-dexamethasone with or without cisplatin in relapsed or refractory mantle cell lymphoma
Ann. Onc.,
February 1, 2007;
18(2):
370 - 375.
[Abstract]
[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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
J. E. Romaguera, L. Fayad, M. A. Rodriguez, K. R. Broglio, F. B. Hagemeister, B. Pro, P. McLaughlin, A. Younes, F. Samaniego, A. Goy, et al.
High Rate of Durable Remissions After Treatment of Newly Diagnosed Aggressive Mantle-Cell Lymphoma With Rituximab Plus Hyper-CVAD Alternating With Rituximab Plus High-Dose Methotrexate and Cytarabine
J. Clin. Oncol.,
October 1, 2005;
23(28):
7013 - 7023.
[Abstract]
[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. E. Witzig, S. M. Geyer, I. Ghobrial, D. J. Inwards, R. Fonseca, P. Kurtin, S. M. Ansell, R. Luyun, P. J. Flynn, R. F. Morton, et al.
Phase II Trial of Single-Agent Temsirolimus (CCI-779) for Relapsed Mantle Cell Lymphoma
J. Clin. Oncol.,
August 10, 2005;
23(23):
5347 - 5356.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
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]
|
|
|
|
|
|
|
A. K. Ganti, P. J. Bierman, J. C. Lynch, R. G. Bociek, J. M. Vose, and J. O. Armitage
Hematopoietic stem cell transplantation in mantle cell lymphoma
Ann. Onc.,
April 1, 2005;
16(4):
618 - 624.
[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]
|
|
|
|
|
|
|
G. Lenz, M. Dreyling, E. Hoster, B. Wormann, U. Duhrsen, B. Metzner, H. Eimermacher, A. Neubauer, H. Wandt, H. Steinhauer, et al.
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)
J. Clin. Oncol.,
March 20, 2005;
23(9):
1984 - 1992.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Fisher
Mantle Cell Lymphoma: At Last, Some Hope for Successful Innovative Treatment Strategies
J. Clin. Oncol.,
February 1, 2005;
23(4):
657 - 658.
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. Goy, A. Younes, P. McLaughlin, B. Pro, J. E. Romaguera, F. Hagemeister, L. Fayad, N. H. Dang, F. Samaniego, M. Wang, et al.
Phase II Study of Proteasome Inhibitor Bortezomib in Relapsed or Refractory B-Cell Non-Hodgkin's Lymphoma
J. Clin. Oncol.,
February 1, 2005;
23(4):
667 - 675.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. B. Maris, B. M. Sandmaier, B. E. Storer, T. Chauncey, M. J. Stuart, R. T. Maziarz, E. Agura, A. A. Langston, M. Pulsipher, R. Storb, et al.
Allogeneic hematopoietic cell transplantation after fludarabine and 2 Gy total body irradiation for relapsed and refractory mantle cell lymphoma
Blood,
December 1, 2004;
104(12):
3535 - 3542.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. Forstpointner, M. Dreyling, R. Repp, S. Hermann, A. Hanel, B. Metzner, C. Pott, F. Hartmann, F. Rothmann, R. Rohrberg, et al.
The addition of rituximab to a combination of fludarabine, cyclophosphamide, mitoxantrone (FCM) significantly increases the response rate and prolongs survival as compared with FCM alone in patients with relapsed and refractory follicular and mantle cell lymphomas: results of a prospective randomized study of the German Low-Grade Lymphoma Study Group
Blood,
November 15, 2004;
104(10):
3064 - 3071.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
W. Brugger, J. Hirsch, F. Grunebach, R. Repp, P. Brossart, W. Vogel, H.-G. Kopp, M. G. Manz, M. Bitzer, G. Schlimok, et al.
Rituximab consolidation after high-dose chemotherapy and autologous blood stem cell transplantation in follicular and mantle cell lymphoma: a prospective, multicenter phase II study
Ann. Onc.,
November 1, 2004;
15(11):
1691 - 1698.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Bendandi, S. A. Pileri, and P. L. Zinzani
Challenging paradigms in lymphoma treatment
Ann. Onc.,
May 1, 2004;
15(5):
703 - 711.
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Belhadj, M.-H. Delfau-Larue, T. Elgnaoui, F. Beaujean, J.-L. Beaumont, C. Pautas, I. Gaillard, Y. Kirova, A. Allain, P. Gaulard, et al.
Efficiency of in vivo purging with rituximab prior to autologous peripheral blood progenitor cell transplantation in B-cell non-Hodgkin's lymphoma: a single institution study
Ann. Onc.,
March 1, 2004;
15(3):
504 - 510.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Mangel, H. A. Leitch, J. M. Connors, R. Buckstein, K. Imrie, D. Spaner, M. Crump, N. Pennell, A. Boudreau, and N. L. Berinstein
Intensive chemotherapy and autologous stem-cell transplantation plus rituximab is superior to conventional chemotherapy for newly diagnosed advanced stage mantle-cell lymphoma: a matched pair analysis
Ann. Onc.,
February 1, 2004;
15(2):
283 - 290.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
R. I. Fisher, T. P. Miller, and O. A. O'Connor
Diffuse Aggressive Lymphoma
Hematology,
January 1, 2004;
2004(1):
221 - 236.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
M. Coleman, D. M. Goldenberg, A. B. Siegel, J. C. Ketas, M. Ashe, J. M. Fiore, and J. P. Leonard
Epratuzumab: Targeting B-Cell Malignancies through CD22
Clin. Cancer Res.,
September 1, 2003;
9(10):
3991S - 3994.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
A. M. Gianni, M. Magni, M. Martelli, M. Di Nicola, C. Carlo-Stella, S. Pilotti, A. Rambaldi, S. Cortelazzo, C. Patti, G. Parvis, et al.
Long-term remission in mantle cell lymphoma following high-dose sequential chemotherapy and in vivo rituximab-purged stem cell autografting (R-HDS regimen)
Blood,
July 15, 2003;
102(2):
749 - 755.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. Boye, T. Elter, and A. Engert
An overview of the current clinical use of the anti-CD20 monoclonal antibody rituximab
Ann. Onc.,
April 1, 2003;
14(4):
520 - 535.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
K. Branson, R. Chopra, P. D. Kottaridis, G. McQuaker, A. Parker, S. Schey, R. K. Chakraverty, C. Craddock, D. W. Milligan, R. Pettengell, et al.
Role of Nonmyeloablative Allogeneic Stem-Cell Transplantation After Failure of Autologous Transplantation in Patients With Lymphoproliferative Malignancies
J. Clin. Oncol.,
October 1, 2002;
20(19):
4022 - 4031.
[Abstract]
[Full Text]
[PDF]
|
|
|
|
|
|
|
J. M. Vose, B. C.-H. Chiu, B. D. Cheson, J. Dancey, and J. Wright
Update on Epidemiology and Therapeutics for Non-Hodgkin's Lymphoma
Hematology,
January 1, 2002;
2002(1):
241 - 262.
[Abstract]
[Full Text]
|
|
|
|
