Phase I Study of Rituximab-CHOP Regimen in Combination with Granulocyte Colony-Stimulating Factor in Patients with Follicular Lymphoma

Abstract

Purpose: Rituximab is an anti-CD20 monoclonal antibody, and it is used to treat B-cell lymphomas. Antibodydependent cellular cytotoxicity (ADCC) is considered one of the mechanisms through which rituximab exerts its effects. Granulocyte colony-stimulating factor (G-CSF) enhances the cytotoxicity of neutrophils through ADCC, and it can be speculated that a combination of rituximab and G-CSF may augment the treatment efficacy of rituximab.Experimental Design: We administered rituximab with CHOP (cyclophosphamide, doxorubicin, vincristine, prednisone) treatment with G-CSF to 15 patients with follicular lymphoma, and we investigated the safety and efficacy of this regimen. We investigated ADCC activity in neutrophils and the expression of cell surface antigens including Fc␥ receptor type I [Fc␥RI (CD64)] on neutrophils to determine the optimal dose of G-CSF.Results: Adverse reactions occurred in 14 of 15 patients and consisted mainly of grade 3/4 hematological toxicity. The response rate was 100%, with complete remission in 12 patients (80%) and partial remission in 3 patients (20%). At 14 months, the median length of the observation period, 2 of 12 patients had relapsed. G-CSF administration increased both Fc␥RI expression and ADCC activity. There were no significant differences in the levels of Fc␥RI expression or ADCC activity between the 2 g/kg G-CSF and 5 g/kg G-CSF groups, indicating that the optimal dose of G-CSF was 2 g/kg. Conclusions:We conclude that the combination of rituximab-CHOP and G-CSF is well tolerated. We plan to carry out a randomized trial to compare efficacy between rituximab-CHOP treatment and treatment with a combination of rituximab-CHOP and G-CSF.

Anti-BR3 antibodies: a new class of B-cell immunotherapy combining cellular depletion and survival blockade

“…[40][41][42] In addition to intrinsic molecule improvements, combinations of B-cell-depleting agents with molecules enhancing other arms of the immune system including effector mechanisms for B-cell depletion (eg, interferon-␣, granulocyte-colony-stimulating factor, granulocyte macrophagecolony-stimulating factor, interleukin 2) are being attempted in B-cell malignancies with variable success. [43][44][45][46] Based on the demonstrated synergy between B-cell depletion and blockade of B-cell survival through BR3, we developed anti-BR3 antibodies that combine, in one molecule, the abilities to deplete B cells and to block BAFF-mediated B-cell survival. These antibodies combine 2 mechanisms of action and show increased in vivo B-cell reduction in some subsets compared with anti-CD20 mAb-mediated B-cell depletion or BAFF-dependent survival blockade on their own.…”

Human Anti-CD40 Antagonist Antibody Triggers Significant Antitumor Activity against Human Multiple Myeloma

“…Despite the impressive responses to rituximab in lowgrade, follicular lymphoma (12), responses to rituximab in multiple myeloma occur only in those 20% of patients whose tumor expresses CD20 (16). Ongoing efforts to improve rituximab treatments for B-cell malignancies include its use with other biological agents (17,18), with chemotherapy (19,20) and with mAbs that target antigens other than CD20.…”

Transplantation and cancer

“…Plusieurs é tudes ont montré que le rituximab (un anticorps anti-CD20) est efficace dans le traitement de ces né oplasies, mê me si le nombre de cures et l'association avec une chimiothé rapie standard ne sont pas encore codifié s [8,14].…”