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Monoclonal antibodies in the treatment of non-Hodgkin’s lymphoma: moving targets

Abstract:

In 1997 rituximab, a chimeric monoclonal anti-CD20 antibody, was the first monoclonal antibody to be approved by the US Food and Drug Administration (FDA), based on the results of a rather limited phase II trial in 166 patients with relapsed/refractory follicular lymphoma. In the last decade the impressive results of a substantial number of randomised clinical trials have totally changed treatment paradigms in B-cell non-Hodgkin’s lymphomas. Importantly, its widespread use and associated commercial success have also given an enormous boost to the development of other monoclonal antibodies. As of 2009, the combination of rituximab and chemotherapy (R-Chemo) is the standard of care for remission induction treatment for both follicular lymphoma and diffuse large B-cell lymphoma because it results in a significantly better progression-free and overall survival than chemotherapy alone. 2-5 In relapsed follicular lymphoma, this should be followed by rituximab maintenance treatment. 6 However, resistance develops in about 50% of previously sensitive patients. Possible mechanisms of rituximab resistance are shown in table 1. Two interesting papers address novel treatment options for rituximab-resistant patients. 7, 8 In the July/August issue of the Netherlands Journal of Medicine, Meerten and Hagenbeek discuss the second-and third-generation anti-CD20 antibodies. These antibodies differ from rituximab in their capacity to differentially activate the three possible effector mechanisms of monoclonal antibodies: antibody-dependent cellular cytotoxicity, complement-dependent cytotoxicity, and direct induction of apoptosis. The key question of …