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Clinical Trial
. 2008 Jun 1;26(16):2725-31.
doi: 10.1200/JCO.2007.13.7729. Epub 2008 Apr 21.

Granulocyte-macrophage colony-stimulating factor potentiates rituximab in patients with relapsed follicular lymphoma: results of a phase II study

Guillaume Cartron  1 , Lu Zhao-Yang, Marion Baudard, Tarik Kanouni, Valérie Rouillé, Philippe Quittet, Bernard Klein, Jean-Francois Rossi
Affiliations
Clinical Trial

Granulocyte-macrophage colony-stimulating factor potentiates rituximab in patients with relapsed follicular lymphoma: results of a phase II study

Guillaume Cartron et al. J Clin Oncol. .

Abstract

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 Fc gamma RIIa- and Fc gamma RIIIa-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 microg/kg/d on days 1 to 8 and rituximab 375 mg/m(2) 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.

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Figures

Figure 1
Figure 1
Treatment regimen for GM-CSF plus rituximab. Patients were treated with subcutaneous GM-CSF (Leucomax®) 5 μg/kg/day from day 1 through day 8, with the addition of rituximab (MabThera®) intravenously at 375 mg/m2 on day 5. Patients received this 8-day regimen every 21 days for a total of four courses. IV, intravenous; SC, subcutaneous.
Figure 2
Figure 2
Progression-free survival in patients with relapsed follicular lymphoma treated with rituximab and GM-CSF (n = 29). (A) In all patients. (B) Based on FLIPI risk at relapse. (C) Based on the quality of the clinical response. (D) Based on the number of cycles of treatment. One cycle was defined as four courses of rituximab and GM-CSF treatment.
Figure 3
Figure 3
Effect of GM-CSF plus rituximab treatment on mean cell counts (± SD) before and after treatment (*P< .05). mDC, myeloid dendritic cell; pDC, plasmacytoid dendritic cell; SD, standard deviation; WBC, white blood cell.
Figure 4
Figure 4
Ratio of mean cell counts after versus before treatment according to response for CR patients and non-CR (PR + SD + PD) patients (*P < .05). CR, complete response; mDC, myeloid dendritic cell; pDC, plasmacytoid dendritic cell; PD, progressive disease; PR, partial response; SD, stable disease; WBC, white blood cell.
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