Maintenance Therapy With Rituximab
Dear OncoLink "Ask The Experts,"
I was diagnosed with follicular non-Hodgkin's stage 3 lymphoma. After FND chemotherapy (F= Fludarabine, N = Nitoxantrone, D= Dexamethasone). I have received Rituximab and have continued on it every 6 months. How long should the maintenance doses be continued? Will this cause a resistance to the drug?
Babis (Charalambos) Andreadis, MD, Assistant Professor in Medicine in the Division of Hematology/Oncology at the Abramson Cancer Center and an Associate Scholar in the Center for Clinical Epidemiology and Biostatistics at the University of Pennsylvania, responds:
Rituximab is a humanized monoclonal antibody against the CD20 antigen that is present on normal as well as malignant lymphocytes. It has had a remarkable impact on the treatment of several lymphomas, including low-grade non-Hodgkin's lymphoma. Several studies have clearly established the activity of Rituximab, either as single agent or in combination with chemotherapy. There are also emerging data as to the use of Rituximab in maintenance treatment, after the achievement of partial or complete response to initial therapy.
Following Rituximab monotherapy (that is, treatment with only Rituximab), we know that 4 weekly doses of Rituximab maintenance, administered every 6 months for 2 years, significantly prolongs the length of remission, but not overall survival, in patients with follicular lymphoma. At the most recent meeting of the American Society of Hematology (ASH 2005), 2 additional studies were presented that extend these findings to patients treated with combination chemotherapy and Rituximab. The study of the German Low Grade Lymphoma Group examined Rituximab maintenance following treatment with FCM+/- Rituximab in 174 patients, and demonstrated a prolongation of remission. The European intergroup study examined Rituximab maintenance following CHOP+/- Rituximab in 268 patients, and showed a prolongation of remission and a longer survival.
Although neither of these studies are formally finished or published, they add to a growing body of knowledge that Rituximab maintenance has a significant remission benefit in this disease. Whether this translates to an advantage in patient survival is a question that cannot yet be answered definitively. These benefits need to be balanced by potential risks, which include issues of both drug resistance and side effects. There is a theoretical risk of resistance to Rituximab, other monoclonal antibodies, and radio-monoclonal antibodies, that is thought to occur in patients who progress while on this drug. Most of the patients in these studies did not have the option of other therapies available to them, so the studies may overestimate the benefit of Rituximab maintenance. Lastly, long-term Rituximab use has been associated with a decrease in serum antibody levels, which can predispose to serious infections. Ultimately, the decision rests with the patients and physicians at this time. It should be noted that all maintenance studies have only given Rituximab for up to 2 years.