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).
Epratuzumab (hLL2 [LymphoCide]), a humanized monoclonal antibody directedagainst the B-cell specific antigen CD22, has been demonstrated to be a safe andactive monotherapy in phase I/II trials for the treatment of relapsed andrefractory non-Hodgkin’s lymphoma (NHL). Given the potential for synergy withother biologic agents, we have conducted a phase II trial to examine the safetyand efficacy of the combination of epratuzumab with rituximab (Rituxan), achimeric anti-CD20 antibody, for the treatment of NHL.
A total of 18 patients have been enrolled and treated on study, 12 of whichare currently evaluable for safety only. Half of evaluable patients were overage 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 histologiesinclude diffuse large B cell (3 patients), follicular (8), and marginal zone(1). The treatment regimen included four weekly infusions of epratuzumab (360mg/m²/wk over 60 minutes) and rituximab (375 mg/m²/wk over 4 to 6 hours).Acetaminophen and diphenhydramine premedication was administered, and in theinitial cohort (six patients), epratuzumab was administered on day 1, rituximabon day 3, and both drugs on days 8, 15, and 22. In cohort 2, both drugs (epratuzumabfollowed by rituximab) were provided on days 1, 8, 15, and 22.
Most treatment-related adverse events occurred with the first week’sinfusion, and all were grade 1/2. No infusion reaction required termination ofinfusion, and no drug-related serious adverse events were observed. The mostfrequently reported adverse events were chills/rigors (5/12, 42%), fever (4/12,34%), and nausea and flushing (3 patients each, 25%). Other less commontreatment-related adverse events (reported in one or two patients only) wereabdominal pain, dyspnea, fatigue, and headache. One patient who received theweek 1 infusions separated by 48 hours had no adverse events. The majority ofinfusion-related events appeared to be temporally related to rituximab infusion,although with the sequential nature of the treatment, drug attribution isunclear.
Given the delayed time to response with biologic agents, efficacy results arepremature with a limited number of evaluable patients, but to date fiveobjective responses have been observed, all of which are complete responses.
CONCLUSION: These preliminary data demonstrate that the addition ofepratuzumab into a combination regimen does not appear to alter the known safetyprofile of rituximab. This combination monoclonal antibody therapeutic regimenappears feasible, has promising activity, and warrants further evaluation inlarger clinical studies in NHL.