A new study published in the Journal of Clinical Oncology (19:3918-3928, 2001) reported that radioimmunotherapy with tositumomab/iodine-131 tositumomab (Bexxar), produced more durable complete or partial clinical responses in patients with low-grade and transformed low-grade non-Hodgkin’s lymphoma (NHL) than did their last round of chemotherapy. All patients in the study had chemotherapy-refractory NHL. Typically, response rates and durations of response in refractory patients decline with each successive therapy, but in this study, the tositumomab/iodine-131 tositumomab combination was shown to reverse the expected outcome.
"Bexxar therapy has resulted in durable remissions in a low-grade NHL population refractory to chemotherapy, and in those with transformed low-grade NHLan aggressive form of lymphoma that is associated with a very poor prognosis," said Mark S. Kaminski, md, professor of internal medicine and codirector of the leukemia/lymphoma bone marrow transplant program at the University of Michigan Cancer Center. "The results of this study demonstrate a measurable improvement over previous therapy and suggest a reversal of the downward trend seen in relapsed and refractory patients following prior treatments."
Significantly Higher Response Rates
The study investigated the safety and efficacy of tositumomab/iodine-131 tositumomab compared to the patient’s previous chemotherapy. Researchers observed a partial or complete response to the investigational combination in 65% of patients vs a 28% response rate to the patient’s last chemotherapy agent. Results for patients achieving a complete response were 20% after tositumomab/iodine-131 tositumomab compared to 3% after treatment with their previous drug. For patients who achieved a complete response with tositumomab/iodine-131 tositumomab, the median duration of response has not yet been reached, and 9 of the 12 patients with complete responses have ongoing responses ranging from 32.3 to 47.4 months.
"Bexxar demonstrated a high rate of response and a low rate of hematologic toxicity in a heavily treated patient population," said Dr. Kaminski.
Tositumomab/iodine-131 tositumomab combines the targeting ability of a monoclonal antibody and the therapeutic potential of radiation, with patient-specific dosing. The radiolabeled monoclonal antibody attaches to the target marker CD20 found on NHL cells, thereby eliciting an immune response and delivering a dose of iodine-131 radiation to tumor cells.
"This targeted approach was designed to ensure that the tumor cells will receive a greater concentration of the therapeutic radiation than normal tissues, and the radioactive component is probably a major factor in the drug’s antitumor effect," said Dr. Kaminski.