Epratuzumab Active in Indolent Lymphomas

NEW ORLEANS—Epratuzumab (LymphoCide), a monoclonal antibody directed against the CD22 antigen, was safe and produced some objective tumor responses in indolent non-Hodgkin’s lymphoma (NHL) in a Phase I/II study. Data from the study were reported in a poster presentation at the ASH meeting by John P. Leonard, MD, of Weill Medical College of Cornell University and New York Presbyterian Hospital, New York. He said that the data suggested that the antibody is a potential new therapy for NHL that may be effective in cases where rituximab (Rituxan) is not.

CD22 is an attractive antigen target because it is B-cell specific, is present on the surface of mature B cells and in the cytoplasm of most B cells, and is rapidly internalized, Dr. Leonard summarized. Epratuzumab is a humanized monoclonal antibody (see Table 1). Dr. Leonard said that epratuzumab reacts with both indolent and aggressive lymphomas but has minimal activity in normal tissue except for the spleen.

 Dose-Escalation Study

This Phase I/II dose-escalation study involved patients who had relapsed after chemotherapy and included 12 patients with indolent lymphomas and 13 with aggressive lymphomas. At least 6 patients (3 indolent and 3 aggressive) were treated with 4 weekly infusions of epratuzumab at each of five dose levels ranging from 120 mg/m² to 600 mg/m² per injection. To date, 30 patients have been enrolled, and 25 have completed treatment. The indolent and aggressive groups were dose-escalated separately.

In patients with indolent lymphomas, epratuzumab produced a 67% objective response rate at dose levels of 360-480 mg/m² x 4 weeks (see Table 2). Responses were seen in aggressive lymphomas at lower dose levels (see Table 3). Interestingly, no responses were seen in aggressive lymphomas at the 360 mg/m² or 480 mg/m² dose levels.

Tolerated at All Dose Levels

“B cells decreased and T cells were variable 4 weeks after treatment [in the responders],” Dr. Leonard reported. No dose-limiting toxicities were observed, and the 1-hour infusions were well-tolerated at all dose levels. Serum immunoglobulin levels were not affected. There was no evidence of pharmacokinetic changes following repeated injections, nor evidence of anti-human antibody response.

Dr. Leonard said that further dose escalation in larger numbers of patients is ongoing to determine the optimal dose of epratuzumab in NHL.