Results of a Phase 2 Multicenter Study of Obinutuzumab plus Bendamustine in Patients with Previously Untreated CLL

Bendamustine plus rituximab is a commonly used first-line treatment for chronic lymphocytic leukemia (CLL), with an overall response rate (ORR) of 96% and complete response (CR) of 31%. But there is substantial opportunity to improve patient outcomes. For instance, obinutuzumab in combination with chlorambucil significantly improved progression-free survival (PFS) and CR rate compared with rituximab and chlorambucil (Goede. 2014). Obinutuzumab is a glycoengineered, type II anti-CD20 monoclonal antibody. As such, this phase 2 study evaluates the efficacy and safety of bendamustine plus obinutuzumab as first-line treatment for patients with CLL.

A total of 102 patients with previously untreated CLL were enrolled. Patients received six 28-day cycles of bendamustine plus obinutuzumab by intravenous infusion. The median patient age was 61 years (range, 35-90 years); 68.6% were male; and 44.1% had Rai stage 3 to 4. The primary end point was CR assessed using International Workshop on CLL criteria. Secondary end points included ORR, PFS, overall survival, and minimal residual disease (MRD). The median follow-up at the time of analysis was 11.0 months.

The CR rate was 49.0% and ORR was 89.2% after 6 cycles. MRD negativity in blood, as measured by 4-color flow cytometry, was achieved in 42.7% of patients at the end of induction-response assessment and in 75.5% of patients at any time after induction. The most frequent adverse events of all grades were infusion-related reactions (72.5%), nausea (52.0%), and pyrexia (36.3%). The most frequent grade 3/4 adverse event was neutropenia (26.5%). The incidence of tumor lysis syndrome (all grade 3) was 4.9%. Three patients died; none of the deaths were related to study treatment or CLL.

Bendamustine plus obinutuzumab is an effective regimen for first-line treatment of patients with CLL, inducing a high CR rate after 6 cycles of therapy. No unexpected safety signals were observed.

Sharman JP, et al. ASCO Abstract 7523.