Purpose:We conducted a single-center, dose-escalation study evaluating the safety, pharmacokinetics, and efficacy of epratuzumab, an anti-CD22 humanized monoclonal antibody, in patients with aggressive non-Hodgkin's lymphoma.Experimental Design: Epratuzumab was administered once weekly for 4 weeks at 120-1000-mg/m 2 doses to 56 patients [most (n ‫؍‬ 35) with diffuse large B-cell lymphoma].Results: Patients were heavily pretreated (median, 4 prior therapies), 25% received prior high-dose chemotherapy with stem cell transplant, and 84% had bulky disease (>5 cm). Epratuzumab was well tolerated, with no doselimiting toxicity. Most (95%) infusions were completed within 1 h. The mean serum half-life was 23.9 days. Across all dose levels and histologies, objective responses (ORs) were observed in five patients (10%; 95% confidence interval, 3-21%), including three complete responses. In patients with diffuse large B-cell lymphoma, 15% had ORs. Overall, 11 (20%) patients experienced some tumor mass reduction. Median duration of OR was 26.3 weeks, and median time to progression for responders was 35 weeks. Two responses are ongoing at >34 months, including one rituximab-refractory patient.Conclusions: These data demonstrate that epratuzumab has a good safety profile and exerts antitumor activity in aggressive non-Hodgkin's lymphoma at doses of >240 mg/m 2 , thus warranting further evaluation in this clinical setting.

Epratuzumab was well tolerated at up to 1,000 mg/m2/wk (for 4 weeks) and had clinical activity. One third of responding patients achieved CR. A 43% objective response rate in follicular NHL patients treated at 360 mg/m2/wk indicates that this dose should be explored in additional studies.