Blinatumomab Shows Promising Activity in Phase I Study of Relapsed NHL

A phase I trial found that blinatumomab, a bispecific T-cell engager (BiTE) antibody, is feasible with regard to safety for the treatment of patients with relapsed or refractory non-Hodgkin lymphoma (NHL). The agent showed anti-lymphoma activity in the trial.

“Since the monoclonal antibody rituximab became an integral part of treatment regimens for B-cell NHL, patient outcomes have improved significantly. However, both early relapse and refractory disease remain associated with a dismal prognosis,” wrote study authors led by Maria-Elisabeth Goebeler, MD, of Wurzburg University Hospital in Germany. Blinatumomab targets both the CD3c subunit of the T-cell receptor complex and the B-cell differentiation antigen CD19, and previous work has shown some activity in other malignancies.

The new study was a phase I dose-escalation trial in 76 heavily pretreated relapsed/refractory NHL patients; 42 of those actually received treatment in the dose-escalation phase. The results of the trial were published online ahead of print in the Journal of Clinical Oncology.

The median number of pretreatment regimens was three, and 93% of patients had previously received rituximab. Five of 42 patients experienced a dose-limiting toxicity, primarily neurologic in nature; the maximum tolerated dose was established at 60 µg/m²/day.

Grade 3 adverse events (AEs) occurred in 90% of patients, grade 4 AEs in 66%, and grade 5 AEs in 4%, regardless of the cause. The most common AEs included lymphopenia, pyrexia, increased C-reactive protein level, and others.

The full 76-patient cohort was included in an analysis of response to blinatumomab. At the dose of 60 µg/m²/day (35 patients), the overall response rate was 69%, with 37% complete responses and 31% partial responses. At lower doses of 15 µg/m²/day and 30 µg/m²/day (21 patients), there were four observed responses, and none at doses below 15 µg/m²/day.

The authors noted that at the optimal dose, blinatumomab showed “notable single-agent activity” specifically in patients with follicular lymphoma, mantle cell lymphoma, and diffuse large B-cell lymphoma (DLBCL). The median response duration for patients who received the target dose was 404 days, and 12 patients had long-term remissions of more than 1 year.

“Single-agent blinatumomab showed promising anti-lymphoma activity in relapsed/refractory NHL,” the authors concluded. On the strength of these results, a phase II study of the agent is underway in patients with relapsed/refractory DLBCL.