Originally published as JCO Early Release 10.1200/JCO.2007.13.7729 on April 21 2008

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Granulocyte-Macrophage Colony-Stimulating Factor Potentiates Rituximab in Patients With Relapsed Follicular Lymphoma: Results of a Phase II Study

Guillaume Cartron, Lu Zhao-Yang, Marion Baudard, Tarik Kanouni, Valérie Rouillé, Philippe Quittet, Bernard Klein, Jean-Francois Rossi

From the Service d'Hématologie et d'Oncologie Médicale, Centre Hospitalier Universitaire (CHU) Montpellier; L'Institut National de la Santé et de la Recherche Médicale (INSERM) U847; Institut de Recherche en Biothérapie, Université Montpellier I; and the Unit of Cellular Therapy, CHU Montpellier, France

Corresponding author: Jean-Francois Rossi, MD, PhD, CHU Montpellier, Service d'Hématologie et d'Oncologie Médicale, CHU Lapeyronie, Avenue du Doyen Giraud, 34295 Montpellier Cedex, France; e-mail: jf-rossi{at}chu-montpellier.fr

Purpose: We hypothesized that granulocyte-macrophage colony-stimulating factor (GM-CSF) could potentiate the clinical activity of rituximab given its individual and cooperative effects on FcRIIa- and FcRIIIa-expressing cells. A phase II clinical study combining GM-CSF and rituximab was initiated in patients with relapsed follicular lymphoma (FL) to determine the clinical and biologic responses, as well as safety of the combination.

Patients and Methods: Thirty three patients with relapsed FL were treated with GM-CSF 5 µg/kg/d on days 1 to 8 and rituximab 375 mg/m² on day 5 of each 21-day cycle for four cycles. Clinical response and tolerability were examined according to international criteria. Biologic monitoring included evaluation of immune cells involved in rituximab activity.

Results: Of 33 evaluated patients, a 70% overall response rate (complete response plus complete response unconfirmed, 45%) and a median progression-free survival (PFS) of 16.5 months were achieved. Outcome was influenced by the quality of response and the Follicular Lymphoma International Prognostic Index (FLIPI), where low- and intermediate-risk FLIPI groups were associated with significantly better PFS. After treatment there was a significant increase in granulocyte and monocyte counts. Examination of dendritic cell response showed an overall increase in plasmacytoid dendritic cells, especially in non-complete response patients, after treatment. Addition of GM-CSF did not impair tolerance to rituximab, and adverse events were rare and mild.

Discussion: GM-CSF plus rituximab results in high response rates, along with a tolerable safety profile in patients with relapsed or progressive FL. The improved efficacy over rituximab monotherapy may be due to increases seen in monocyte, granulocyte, and dendritic cell populations.

published online ahead of print at www.jco.org on April 21, 2008.

Supported in part by grants from the Ligue Nationale Contre Le Cancer (équipe labellisée), Paris, France, and by Bayer Healthcare Pharmaceuticals Inc.

Presented in part at the 47th Annual Meeting of the American Society of Hematology, Atlanta, GA, December 10-13, 2005.

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