GM-CSF plus rituximab immunotherapy: translation of biologic mechanisms into therapy for indolent B-cell lymphomas

Historically, patients with indolent non-Hodgkin lymphomas (NHL) have been treated with radiotherapy, chemotherapy or a combination of these therapies. The introduction of biologic agents, most notably rituximab, a monoclonal antibody targeting cell-surface CD20 present on B-cell NHL cells, has enhanced patient response rates; however, relapse continues to limit long-term disease-free survival. Recent advances in the treatment of patients with indolent B-cell NHL have taken two directions--combining rituximab with chemotherapy or enhancing rituximab-mediated mechanisms of action. The combination of rituximab with the cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) takes the second approach and appears to lead to improved patient responses over rituximab monotherapy without compromising its tolerability profile. GM-CSF functions by increasing the numbers and cytotoxic activity of effector cells, perhaps in part by increasing the expression of some cell surface molecules (i.e., receptors, antigens). The combined biologic effects of GM-CSF and rituximab appear promising in that they might enhance a patient's inherent immune response against malignant cells. The biologic effects of these individual and combined immunotherapeutic agents, with or without chemotherapy, and their translation into patient outcomes are reviewed here.