Phase I/II Trial Results Of 131-I-Anti-B1 (Anti-CD20) Non-Myeloablative Radioimmunotherapy For Refractory B-Cell Lymphoma
Researchers at the University of Michigan Medical Center (Ann Arbor, MI) presented results of a Phase I/II clinical trial of a new form of treatment for non-Hodgkin's lymphoma. There are approximately 51,000 new cases of non-Hodgkin's lymphoma in the U.S. each year.
Chemotherapy and radiotherapy have been the mainstays of lymphoma treatment. Radioimmunotherapy refers to the use of intravenous injections of monoclonal antibodies which have been tagged with radioisotopes. These radioisotopes target radiation to tumors displaying a specific chemical structure to which monoclonal antibodies can selectively attach. The selective binding ability of the radioactive monoclonal antibodies results in a greater accumulation of radiation in tumor sites, minimizing the cell-killing effects of radiation on normal tissue and maximizing them in tumor sites.
In the trial, 47 patients with B-cell lymphoma that had previously received chemotherapy and failed treatment, were given a monoclonal antibody called anti-B1 to which radioactive iodine was chemically attached. Anti-B1 selectively binds to a protein on the exterior surface of more than 95% of all B-cell lymphomas and on a subset of normal B cells, but not on any other cells of the body.
Patients received an initial tracer dose injection of anti-B1 with a small amount of 131-I attached. Patients were evaluated over one week to measure how well the radioactive antibody targeted tumors and the rate at which the radioactivity cleared the body. A therapeutic dose was then injected and adjusted to deliver a specific dose of radiation to the whole body based on the clearance rate of each patient's tracer dose. In addition, an injection of non-radioactive anti-B1 was given to optimize the targeting of the radioactive antibody.
Results presented by Mark S. Kaminski, M.D., associate professor, University of Michigan Medical Center, indicate that radioimmunotherapy with radioactive anti-B1 represents a promising, well-tolerated treatment. In this study, 72% of patients had complete or partial remission (a greater than 50% shrinkage in disease.) The complete remissions have lasted an average of at least 16 months, with a range of four to 38 months. Side effects were generally limited to reversible declines in blood counts. This treatment may be particularly effective (90% remission) in patients with low-grade lymphoma who have failed multiple chemotherapy treatments. These patients have limited treatment options.
"This research represents an exciting step forward in the treatment of disease with monoclonal antibodies," said Ellin Berman, M.D., associate professor, Memorial Sloan-Kettering Cancer Center (New York, NY) at a press briefing today. "While this research is in its early stages, it may potentially provide clinicians with the ability to better manage, and hopefully cure, chemotherapy-resistant patients."