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 (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 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
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.