Originally published as JCO Early Release 10.1200/JCO.2006.06.4618 on April 9 2007

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Rituximab Added to First-Line Mitoxantrone, Chlorambucil, and Prednisolone Chemotherapy Followed by Interferon Maintenance Prolongs Survival in Patients With Advanced Follicular Lymphoma: An East German Study Group Hematology and Oncology Study

Michael Herold, Antje Haas, Stefanie Srock, Sabine Neser, Kathrin Haifa Al-Ali, Andreas Neubauer, Gottfried Dölken, Ralph Naumann, Wolfgang Knauf, Mathias Freund, Robert Rohrberg, Klaus Höffken, Astrid Franke, Thomas Ittel, Erika Kettner, Ursula Haak, Ulrich Mey, Christian Klinkenstein, Michael Aßmann, Ullrich von Grünhagen

From the HELIOS Klinikum Erfurt GmbH, Erfurt; Klinikum Ernst von Bergmann, Potsdam; Charité, Rudolph-Virchow-Klinikum; Charité, Campus Klinikum Benjamin Franklin, Berlin; Klinikum Chemnitz, Chemnitz; Klinikum der Universität Leipzig, Leipzig; Klinikum der Philips Universität Marburg, Marburg; Klinikum der Ernst-Moritz-Arndt Universität, Greifswald; Klinikum der Technischen Universität Dresden, Dresden; Onkologische Schwerpunktpraxis Frankfurt/Main, Frankfurt/Main; Klinikum der Universität Rostock, Rostock; Onkologische Schwerpunktpraxis; Städitisches Krankenhaus Martha-Maria Halle-Dölau, Halle; Klinikum der Friedrich-Schiller-Universität, Jena; Klinikum der Otto-von-Guericke-Universität; Städtisches Klinikum Magdeburg, Magdeburg; Klinikum der Hansestadt Stralsund GmbH, Stralsund; Klinikum der Rheinischen Friedrich-Wilhelms Universität Bonn, Bonn; Klinikum Frankfurt/Oder, Frankfurt; Krankenhaus Riesa, Riesa; and Onkologische Schwerpunktpraxis, Cottbus, Germany

Address reprint requests to Michael Herold, MD, HELIOS Klinikum Erfurt GmbH, 2 Medizinische Klinik, Bereich Hamatologie/Onkologie, Nordhauserstr 74, 99089, Erfurt, Germany; e-mail: miherold{at}erfurt.helios-kliniken.de

Purpose Rituximab has been shown to be active in follicular lymphoma (FL), both as monotherapy and in combination with chemotherapy. We conducted a randomized trial comparing mitoxantrone, chlorambucil, and prednisolone (MCP) chemotherapy plus rituximab with MCP alone.

Patients and Methods Previously untreated patients with stage III or IV CD20⁺ indolent or mantle cell lymphoma were randomly assigned to either eight 28-day cycles of MCP plus rituximab (R-MCP; n = 181) or eight cycles of MCP alone (n = 177). All patients who achieved a complete or partial remission were treated with interferon maintenance until relapse. Herein, we report the results from the primary analysis population of patients with FL, who constituted the majority of patients (56%) recruited to the trial (n = 201; R-MCP, n = 105; MCP, n = 96).

Results Rates of overall and complete response were significantly higher in the R-MCP arm than the MCP arm (overall response, 92% v 75%, respectively; P = .0009; complete response, 50% v 25%, respectively; P = .004). With a median follow-up time of 47 months, median event-free survival (EFS) and progression-free survival (PFS) times were significantly prolonged with R-MCP compared with MCP (EFS, not reached v 26 months, respectively; P < .0001; PFS, not reached v 28.8 months, respectively; P < .0001), and overall survival (OS) was significantly improved with R-MCP compared with MCP (4-year OS rate, 87% v 74%, respectively; P = .0096).

Conclusion The R-MCP regimen significantly improves complete and overall response rates, EFS, PFS, and OS in patients with previously untreated advanced FL, without a clinically significant increase in toxicity.

published online ahead of print at www.jco.org on April 9, 2007.

Supported by grants from F. Hoffmann–La Roche Ltd, Germany.

Presented in part at the 46th Annual Meeting of the American Society of Hematology, December 4-7, 2004, San Diego, CA; the 9th International Conference on Malignant Lymphoma, June 8-11, 2005, Lugano, Switzerland; and the 48th Annual Meeting of the American Society of Hematology, December 9-12, 2006, Orlando, FL.

Authors' disclosures of potential conflicts of interest and author contributions are found at the end of this article.

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