Obinutuzumab Outperforms Rituximab in CLL

Peripheral blood film from a 70-year-old woman with an absolute lymphocyte count of 41,000/uL; source: Ed Uthman, Wikimedia Commons

In a new study, combining the anti-CD20 antibody obinutuzumab with the chemotherapeutic agent chlorambucil improved outcomes over rituximab and the same agent in chronic lymphocytic leukemia (CLL) patients with coexisting conditions.

Adding rituximab-also an anti-CD20 antibody-to chemotherapy has been shown to prolong overall survival in CLL patients who are physically fit. “However, randomized trials have not shown that targeting the CD20 antigen in patients with CLL and coexisting conditions would result in a similar benefit,” wrote study authors led by Valentin Goede, MD, of University Hospital Cologne in Germany. Based on preclinical research, the investigators compared obinutuzumab to rituximab in the new trial; results were published January 8 online ahead of print in the New England Journal of Medicine.

The phase III study included a total of 781 patients with previously untreated CLL; all patients had a score above 6 on the Cumulative Illness Rating Scale (CIRS), or a creatinine clearance of 30 to 69 ml/minute, representing poorer health. The median CIRS score was 8 at baseline. Patients were randomized to either chlorambucil alone, obinutuzumab plus chlorambucil, or rituximab plus chlorambucil.

Both of the combination therapy options increased response rates and prolonged progression-free survival over chemotherapy alone. The median progression-free survival was 26.7 months with obinutuzumab, compared with 11.1 months with chlorambucil alone, for a hazard ratio (HR) for progression or death of 0.18 (95% CI, 0.13-0.24; P < .001). Median progression-free survival for the rituximab combination was 16.3 months, also a significant improvement over chemotherapy alone.

Obinutuzumab and chlorambucil prolonged overall survival compared with chemotherapy alone as well, with a HR for death of 0.41 (95% CI, 0.23-0.74; P = .002).

When the two combination regimens were compared directly, obinutuzumab increased progression-free survival significantly over rituximab, with a HR for progression of 0.39 (95% CI, 0.31-0.49; P < .001). There was also a significantly higher rate of complete response with obinutuzumab, at 20.7% vs 7%. Some adverse events were more common with obinutuzumab; specifically, infusion-related reactions and neutropenia occurred more frequently, but risk of infection was similar.

“To date, targeting of the CD20 antigen is the only therapeutic approach that has been shown to prolong survival among patients with previously untreated CLL,” the authors wrote. “This study showed more complete responses and longer progression-free survival with obinutuzumab than with rituximab.” They noted that no strong predictors of infusion-related reaction were seen, so all CLL patients, “irrespective of leukemic burden,” should be closely monitored during the initial infusion.