Epratuzumab is a humanized anti-CD22 monoclonal antibody immunoglobulin G1 (hLL2 [LymphoCide]) that has been studied in radiolabeled forms (iodine-131[131I] and yttrium-90 [90Y]) in the treatment of chemotherapy-refractory non-Hodgkins lymphoma (NHL). The aim of this trial is to assess the safety and efficacy of escalating doses of the naked (unlabeled) form of epratuzumab in patients with NHL who relapsed after chemotherapy.
At least six patients (three with indolent and three with aggressive lymphomas) were treated with four weekly infusions of epratuzumab at each of five dose levels, ranging from 120 to 600 mg/m² per injection. To date, 30 patients have been enrolled, with 25 currently assessable for toxicity and response.
Dose-limiting toxicity has not been observed, and the 1-hour infusions have been tolerated well at all dose levels. No drug-related grade 3 or 4 toxicity has been observed; only grade 2 hypotension (N = 2) and grade 1 rigors and fatigue (N = 3 each) were noted, primarily during the initial infusion. All other drug-related events were only grade 1, including blood count or chemistry changes.
Serum immunoglobulin levels have not been affected, nor has there been evidence of pharmacokinetic changes following repeated injections. There is no evidence of a significant antihuman antibody response.
Reduction in circulating CD22-positive cells has been observed in several patients. No responses were seen at dose level 1 (120 mg/m²/wk). One diffuse large cell lymphoma patient treated at dose level 2 (240 mg/m²/wk), who previously relapsed after chemotherapy and autologous stem-cell transplantation and who was also unresponsive to rituximab(Drug information on rituximab) (Rituxan) therapy, has achieved an ongoing complete remission (CR) for over 1 year. Two of three indolent NHL patients treated at dose level 3 (360 mg/m²/wk) responded (1 CR, 1 partial response [PR]), as well as two of three indolent NHL patients treated at dose level 4 (480 mg/m²/wk; 1 CR, 1 PR). Four of these five responses are ongoing.
Epratuzumab levels were detectable in the serum for up to 3 months after treatment, and patients with objective responses had higher circulating levels.
CONCLUSION: Epratuzumab is well tolerated across a wide range of protein doses given as a 1-hour infusion, and can result in objective tumor responses. These results suggest that the antibody is a potential new therapy for NHL that may be effective in cases of rituximab failure. Further dose escalation in larger numbers of patients is ongoing to determine the optimal dose and response rate.