Immunomedics reported today that epratuzumab labeled with the potent radioisotope, yttrium-90 (Y-90), produced significant clinical results when given in small fractionated doses repeatedly to patients with non-Hodgkin’s lymphoma (NHL) in a multicenter, open-label, dose-escalation study, at the 2008 American Society of Clinical Oncology (ASCO) meeting in Chicago.
The study completed its targeted enrollment of 64 adult patients with documented B-cell NHL, who had failed one or more regimen therapies, including rituximab.
The researchers reported that 61 patients were evaluable with an overall objective response rate of 64 percent and a complete response rate of 49 percent. Complete responses appear durable with 15 patients remaining disease free for more than one year, including five continuing for two to four years. Immunomedics said that both the objective and complete response rates appear to increase with higher cumulative doses.
The investigators reported 16 patients were treated at the highest fractionated dose level, resulting in 37.5 - 40 mCi/m2 total Y-90 administered in two or three doses.
The overall objective response rate was 100 percent, and the complete response rate was 75 percent, according to the Morris Plains, N.J.-based Immonumedics. The company also noted that responses to radioiodine therapy (RAIT) were seen in patients with different types of NHL, in both rituximab-naïve and treated patients, and in the subgroup of patients who had failed to respond to their last therapy, had bulky disease and elevated lactic dehydrogenase.
“This study, we believe, has validated the concept of fractionated RAIT. By splitting the radioactive dose over two or three fractions, we have demonstrated that higher radioactivity can be delivered selectively and locally to lymphoma cells without simultaneously increasing the bone marrow toxicity normally associated with RAIT. The 45 mCi/m2 Y-90 cumulative dose level reported in this study is more than two-fold higher than the maximum allowable dose of 32 mCi currently approved for ibritumomab tiuxetan,” said Cynthia L. Sullivan, president and CEO of Immonumedics.
“We are in the process of formulating a strategy for further development of this agent,” she added.