Mechanisms of Resistance to Rituximab Coming into View

ATLANTA, GA – The fog may be lifting as to the mechanisms of treatment resistance due to a promising therapy for patients with lymphoma, according to a study by researchers in the departments of Medicine and Immunology at Roswell Park Cancer Institute (RPCI).  Francisco J. Hernandez-Ilizaliturri, MD, Department of Medicine, will present this research (abstract # 2516)* at the annual meeting of the American Society of Clinical Oncology, June 2-6, Atlanta, GA.

Approximately 18,840 lymphoma patients will die from their disease in 2006, despite treatment with rituximab, a monoclonal antibody that achieved meaningful clinical responses in 40-50% in Phase II/III studies of previously treated patients with indolent lymphoma.

However, not every patient responds to rituximab and many, if not most patients previously treated with rituximab, eventually relapse with variable degrees of biologically resistant disease. The pathways leading to resistance to rituximab have not been defined to date.

In this study, researchers developed several rituximab-resistant cell lines to elucidate the molecular basis for rituximab failures by identifying the factors implicated in the emergence of resistance to rituximab and developing strategies to overcome them.

They found that resistence to rituximab decreases total CD20 expression and/or structural changes in CD20, expression in the internal domains of the proteins, and decreases the activity of rituximab. In addition, they found an association between rituximab resistance and significant changes in the programmed cell pathways and in the calcium mobilization within lymphoma cells.

Plans are to evaluate and further validate these laboratory findings in cells isolated from lymphoma patients and then develop preclinical and clinical strategies to overcome resistance to rituximab. It is anticipated that the information gained through these studies will permit the design of more effective clinical therapies for rituximab-resistant lymphoma patients.

The American Society of Clinical Oncology is the world’s leading professional organization representing physicians of all oncology subspecialties who care for people with cancer. ASCO’s more than 20,000 members from the United States and abroad set the standard for patient care and lead the efforts to discover more effective cancer treatments, increase funding for clinical and translational research, and ultimately, improve cancer care for the estimated 10 million people diagnosed with cancer worldwide each year.

Roswell Park Cancer Institute, founded in 1898, is the nation’s first cancer research, treatment and education center and is the only National Cancer Institute-designated comprehensive cancer center in Upstate New York. RPCI is a member of the prestigious National Comprehensive Cancer Network, an alliance of the nation’s leading cancer centers. For more information, visit RPCI’s website at www.roswellpark.org, call 1-877-ASK-RPCI (1-877-275-7724) or e-mail askrpci@roswellpark.org.