Epratuzumab, a humanized anti-CD22 antibody, in aggressive non-Hodgkin's lymphoma: Phase I/II clinical trial results

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 (it = 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 (greater than or equal to5 cm). Epratuzumab was well tolerated, with no dose-limiting 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 greater than or equal to34 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 greater than or equal to240 mg/m(2), thus warranting further evaluation in this clinical setting.