Confirmation of Safety, Efficacy and Response Duration in Non-Hodgkin Lymphoma Patients Treated with 60 μg/m²/d of BiTE® Antibody Blinatumomab.

Abstract 2723

Poster Board II-699

Indolent and mantle cell lymphoma (MCL) are predominantly treated with chemotherapy or a combination of chemotherapy with monoclonal antibodies. Despite high initial response rates, eventually almost all patients however relapse, leaving the disease incurable. Moreover, with increasing numbers of regimens administered, the responsiveness of patients is reduced. Blinatumomab is a single-chain bispecific antibody construct with specificity for CD19 and CD3, belonging to the class of bispecific T cell engager (BiTE®). Here, we report on patients in an ongoing phase 1 trial treated at a dose of 60 μg/m²/d for 4–8-week by continuous i.v. infusion with single-agent blinatumomab. In total, 12 patients with indolent mainly follicular lymphoma or MCL were treated at 60 μg/m²/d during the first treatment cycle. 11/12 patients showed an objective response (7 PR and 4 CR). As of July 2009, median response duration was 12 months with 6 out of 11 responses still ongoing. The single non-responding patient experienced a reversible, neurological adverse event leading to early discontinuation of treatment. Of the 11 responders, one patient developed a port infection and 4 patients showed neurological symptoms, which were all fully reversible. In order to mitigate neurological adverse events during first dosing, which can occur in a defined subset of patients, patients were treated for 1–2 weeks with a lower initial dose (5 and/or 15 μg/m²/d) followed by a maintenance dose of 60 μg/m²/d. A lower starting dose appeared to ameliorate initial adverse events to an extent that treatment could be continued without interruption. Taken together, our data confirm a high single-agent activity of 60 μg/m²/d blinatumomab infused for 4–8 week with long lasting remissions and a favorable risk/benefit profile. The confirmed dose will be considered for further clinical development of blinatumomab in follicular lymphoma and MCL. New data on patients treated with a dose of 90 μg/m²/d will be presented.