Antibody Therapy with Rituximab for Patients with Low-Grade Non-Hodgkin’s Lymphoma

Abstract

Rituximab (Mabthera^® , Rituxan^® ) is a genetically engineered chimeric murine/human monoclonal antibody directed against the CD20 antigen found on the surface of normal and malignant B lymphocytes; it has recently been licensed in the United States and Europe as a novel antibody therapy for patients with relapsed or refractory low-grade or follicular, CD20 positive, B-cell non-Hodgkin’s lymphoma (NHL). Preclinical studies have shown that rituximab specifically recognizes the CD20 antigen, can induce human effector mechanisms in vitro, and effectively depletes B cells in cynomolgus monkeys with limited toxicity. Previous clinical studies have demonstrated that 4 infusions of 375 mg/m² rituximab given over a 22-day period in patients with low-grade NHL is effective, with an overall response rate of 50%. Adverse events associated with treatment are primarily mild and are most frequent with the first infusion, decreasing with subsequent infusions. B cells are effectively depleted during treatment: Levels return to normal ranges between 9 and 12 months post-treatment. Immunoglobulin levels of IgM, IgG, and IgA remain within the normal range. A human anti-chimeric antibody response has been detected in only less than 1% of patients treated and has not interfered with treatment. Rituximab offers a novel, effective, well-tolerated alternative treatment for NHL compared with existing therapies. The clinic al success of rituximab reinforces the promising potential of antibody therapy.