Bendamustine in combination with ofatumumab in relapsed or refractory chronic lymphocytic leukemia : a GIMEMA multicenter phase II trial

We conducted a phase II, non-comparative, open-label, multicenter GIMEMA (Gruppo Italiano Malattie EMatologiche dell'Adulto) study (CLL0809) to assess the efficacy and safety of bendamustine in combination with ofatumumab (BendOfa) in relapsed/refractory chronic lymphocytic leukemia (CLL). Forty-seven patients from 14 centers were evaluated. Therapy consisted of bendamustine (70 mg/m2) for two consecutive days every 28 days, and ofatumumab 300 mg on day 1 and 1000 mg on day 8 during the first cycle, and 1000 mg on day 1 subsequently. Treatment was administered up to 6 cycles. The overall response rate (ORR), as per intention-to-treat analysis, was 72.3% (95% CI, 57–84%), with 17% complete responses. After a median follow-up of 24.2 months, the overall survival was 83.6% (95% CI, 73.0–95.7%) and the progression-free survival (PFS) 49.6% (95% CI, 35.9–68.6%). The median PFS was 23.6 months. Univariate and multivariate analyses were used to identify clinical and biological characteristics associated with ORR and PFS. Myelosuppression was the most common toxicity; grade greater than or equal to3 neutropenia was observed in 61.7% of patients, however grade greater than or equal to3 infections occurred in 6% of patients. BendOfa is feasible and effective in relapsed/refractory CLL patients, including patients with high risk clinical and biological features.