Epratuzumab (hLL2 [LymphoCide]), a humanized monoclonal antibody directed against the B-cell specific antigen CD22, has been demonstrated to be a safe and active monotherapy in phase I/II trials for the treatment of relapsed and refractory non-Hodgkin’s lymphoma (NHL). Given the potential for synergy with other biologic agents, we have conducted a phase II trial to examine the safety and efficacy of the combination of epratuzumab with rituximab(Drug information on rituximab) (Rituxan), a chimeric anti-CD20 antibody, for the treatment of NHL.
A total of 18 patients have been enrolled and treated on study, 12 of which are currently evaluable for safety only. Half of evaluable patients were over age 60 (range: 21-84) and 50% had received two or more prior regimens (range: 1 to 5). All patients were rituximab-naive. Non-Hodgkin’s lymphoma histologies include diffuse large B cell (3 patients), follicular (8), and marginal zone (1). The treatment regimen included four weekly infusions of epratuzumab (360 mg/m²/wk over 60 minutes) and rituximab (375 mg/m²/wk over 4 to 6 hours). Acetaminophen and diphenhydramine(Drug information on diphenhydramine) premedication was administered, and in the initial cohort (six patients), epratuzumab was administered on day 1, rituximab on day 3, and both drugs on days 8, 15, and 22. In cohort 2, both drugs (epratuzumab followed by rituximab) were provided on days 1, 8, 15, and 22.
Most treatment-related adverse events occurred with the first week’s infusion, and all were grade 1/2. No infusion reaction required termination of infusion, and no drug-related serious adverse events were observed. The most frequently reported adverse events were chills/rigors (5/12, 42%), fever (4/12, 34%), and nausea and flushing (3 patients each, 25%). Other less common treatment-related adverse events (reported in one or two patients only) were abdominal pain, dyspnea, fatigue, and headache. One patient who received the week 1 infusions separated by 48 hours had no adverse events. The majority of infusion-related events appeared to be temporally related to rituximab infusion, although with the sequential nature of the treatment, drug attribution is unclear.
Given the delayed time to response with biologic agents, efficacy results are premature with a limited number of evaluable patients, but to date five objective responses have been observed, all of which are complete responses.
CONCLUSION: These preliminary data demonstrate that the addition of epratuzumab into a combination regimen does not appear to alter the known safety profile of rituximab. This combination monoclonal antibody therapeutic regimen appears feasible, has promising activity, and warrants further evaluation in larger clinical studies in NHL.