Durable Complete Responses Following Therapy with Epratuzumab Plus Rituximab: Final Efficacy Results of a Multicenter Study in Recurrent Indolent Non-Hodgkin's Lymphoma (NHL).

Abstract

BACKGROUND: Epratuzumab, an anti-CD22 humanized monoclonal antibody, has shown clinical activity as a single-agent (Leonard et al, J Clin Oncol. 2003; 21:3051–3059) and in combination with rituximab in relapsed/refractory B-cell NHL (Leonard et al, J Clin Oncol. 2005; 23:5044–5051). To evaluate this combination regimen in a larger cohort of patients and to evaluate long-term efficacy, we conducted an international multicenter, open-label, single-arm study in patients with recurrent indolent NHL.METHODS: Forty-nine patients (23F/26M, median age: 61, elevated LDH: 25%, bone marrow involvement: 49%) with chemotherapy-relapsed or refractory follicular NHL (n=41) or small lymphocytic lymphoma (n=7) (as well as one enrolled patient with histological evidence of follicular and diffuse large B-cell lymphoma) were evaluated. Thirty-five (71%) were rituximab-naive, with the remainder having previously received and responded to then relapsed from rituximab (single agent or with chemotherapy). Patients received 360 mg/m2 IV of epratuzumab, followed by 375 mg/m2 IV of rituximab, weekly for 4 consecutive weeks.RESULTS: As preliminarily reported (Emmanouilides et al, Blood 2003; 102/11:69a), the combination therapy was well tolerated, without notable additive toxicity over that expected with single-agent rituximab. Twenty-two of the 41 (54%, 95% CI: 37% – 69%) follicular NHL (FL) patients achieved an objective response (OR) using IWG response criteria, including 10 (24%) patients with complete responses (CR), half of whom remained in remission at the last evaluation with a median duration of follow-up of 44.3 months (range: 18.2 – 52.4 months). The median duration of response (DR) was 13.4 months (95% CI: 8.4 – 28.2 months) and the median progression-free survival (PFS) was 10.2 months (95% CI: 6.3 – 13.6 months), with a Kaplan-Meier estimated median DR of 33.4 months (range: 11.2 – 47.9 months) and an estimated median PFS of 35.1 months (range: 12.9 – 52.4 months) for the 10 patients who achieved CR. Importantly, 4/7 SLL patients (57%) experienced OR, including 2 CR, 1 CRu and 1 PR. Furthermore, while the rituximab-naive FL and SLL patients (n=34) showed an OR of 50% (26% CR/CRu, 24% PR), those patients who had responded to prior rituximab (n=14) had an OR of 64% (29% CR, 36% PR).CONCLUSIONS: Overall, this study confirms that the combination of epratuzumab and rituximab, in addition to being well tolerated, demonstrates promising anti-lymphoma activity for indolent NHL, and can result in durable complete remissions in a subset of patients. Further evaluation of this combination regimen as initial therapy for indolent NHL is planned (CALGB 50701), and in diffuse large B cell lymphoma (CHOP + epratuzumab + rituximab) is ongoing (NCCTG N0489).