NEW ORLEANSEpratuzumab (LymphoCide), a monoclonal
antibody directed against the CD22 antigen, was safe and produced
some objective tumor responses in indolent non-Hodgkins
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.
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.