Role of obinutuzumab in the treatment of chronic lymphocytic leukemia

The pharmacology, pharmacokinetics, safety and efficacy, and place in therapy of obinutuzumab in the treatment of chronic lymphocytic leukemia (CLL) are reviewed.

Obinutuzumab, a fully humanized monoclonal antibody that targets the CD20 receptor on mature B cells, was recently approved for use in combination with chlorambucil in patients with previously untreated CLL. In a Phase III clinical trial including 671 patients with CLL and significant comorbidities, patients who received obinutuzumab-chlorambucil combination therapy had longer median progression-free survival than those who received rituximab plus chlorambucil (26.7 months versus 15.2 months, p < 0.001) or chlorambucil alone (11.1 months, p < 0.001). Overall survival was also improved with the use of obinutuzumab-chlorambucil versus chlorambucil alone (hazard ratio for death, 0.41, p = 0.002) and similar to survival with the use of rituximab plus chlorambucil. The main type of adverse effect reported in association with obinutuzumab use is infusion-related reactions (IRRs), which occurred in 66% of patients in the Phase III trial, with 20% of reactions categorized as grade 3 or 4; IRR risk can be reduced with appropriate dosing, premedication, patient monitoring, and immediate treatment of IRRs. Ongoing clinical trials are evaluating the effects of obinutuzumab in patients with newly diagnosed and relapsed or treatment-refractory CLL.

In patients who are elderly or who have multiple comorbidities, the use of obinutuzumab, a CD20 monoclonal antibody, in combination with chlorambucil is an efficacious regimen for treatment-naive patients with symptomatic CLL.