Originally published as JCO Early Release 10.1200/JCO.2004.07.170 on May 24 2004

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Fludarabine Plus Mitoxantrone With and Without Rituximab Versus CHOP With and Without Rituximab As Front-Line Treatment for Patients With Follicular Lymphoma

From the Institute of Hematology and Medical Oncology L. e A. Seràgnoli, University of Bologna, Bologna; Departments of Cellular Biotechnology and Hematology, University La Sapienza of Rome; Department of Hematology, La Cattolica University of Rome; Department of Hematology, Tor Vergata University of Rome, Rome; Department of Hematology, University of Udine, Udine; Department of Hematology, University of Napoli, Napoli; Department of Internal Medicine, University of Bari, Bari; Cesena Hospital, Cesena; Division of Oncology, Forlì Hospital, Forlì; Division of Hematology, Brescia Hospital, Brescia; Division of Hematology, Ravenna Hospital, Ravenna; Chair of Hematology, University of Genova, Genova; Department of Hematology, University of Perugia, Perugia; Division of Oncology, Rimini Hospital, Rimini; Division of Hematology, Latina Hospital, Latina, Italy

Address reprint requests to Pier Luigi Zinzani, MD, Istituto di Ematologia e Oncologia Medica L. e A. Seràgnoli, Policlinico S. Orsola, Via Massarenti 9, 40138 Bologna, Italy; e-mail: plzinzo{at}med.unibo.it

PURPOSE: Promising new therapeutic options for follicular lymphoma (FL) include fludarabine plus mitoxantrone (FM) and the mouse/human anti-CD20 antibody, rituximab. We performed a randomized comparative trial of FM with cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) front-line chemotherapy with and without sequential rituximab.

PATIENTS AND METHODS: All previously untreated CD20⁺ FL patients presenting in 15 Italian cooperative institutions from October 1999 were randomly allocated to FM or CHOP. Following clinical or molecular restaging, patients in complete remission (CR) with bcl-2/IgH negativity (CR^–) received no further treatment; those in CR with bcl-2/IgH positivity (CR⁺) received rituximab, as did those in partial remission (PR) with bcl-2/IgH negativity (PR^–) or positivity (PR⁺); nonresponders (NR subgroup) were off study.

RESULTS: After chemotherapy, the FM arm achieved higher rates of CR (68% [49 of 72 patients] v 42% [29 of 68 patients]; P = .003) and CR^– (39% [28 of 72 patients] v 13 of 68 patients [19%]; P = .001). Rituximab elicited CR^– in 55 of 95 treated patients (58%). The final CR^– rate was higher in the FM arm (71% [51 of 72 patients] v 51% [35 of 68 patients]; P = .01). However, with a median follow-up of 19 months (range, 9 to 37 months), no statistically significant difference was found among the various study arms in terms of both progression-free (PFS) and overall survival (OS).

CONCLUSION: These results indicate that FM is superior to CHOP for front-line treatment of FL and that rituximab is an effective sequential treatment option. However, they also confirm that this superiority is unlikely to translate into either better PFS or OS.

Supported by a grant from Fondazione del Monte di Bologna e Ravenna.

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

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