Will Obinutuzumab Replace Rituximab for CLL Combination Treatment?
Researchers are attempting to identify treatment strategies that would allow for shorter therapy duration. Obinutuzumab, in combinations, may represent one of those strategies.
Before the 2010 US Food and Drug Administration (FDA) approval of the anti-CD20 antibody, rituximab, the mainstay of treatment for patients with chronic lymphocytic leukemia (CLL) was chemotherapy. While rituximab with chemotherapy significantly improved survival rates, the majority of patients still eventually relapse.
The next-generation anti-CD20 antibody, obinutuzumab, was developed to attempt deeper and longer-lasting remission compared with rituximab.
“Obinutuzumab is an anti-CD20 monoclonal antibody that has been glycoengineered to have a reduced fucose content,” Nadia Khan, MD, assistant professor in the department of hematology/oncology at Fox Chase Cancer Center in Philadelphia, Pennsylvania, told Cancer Therapy Advisor. “The result of this engineering is really an antibody that binds to the immune effector cells in a slightly more efficient way than rituximab, and results in enhanced antibody dependent cellular cytotoxicity (ADCC).”
The FDA approved obinutuzumab in 2013 for use in combination with chlorambucil for patients with previously untreated CLL.1
The approval was based on the results of the CLL11 trial (ClinicalTrials.gov Identifier: NCT01010061), which demonstrated an improved progression-free survival (PFS) with obinutuzumab plus chlorambucil.2 The trial included patients with untreated CLL and coexisting conditions. Patients were randomly assigned to chlorambucil only or to chlorambucil plus obinutuzumab or rituximab.
Treatment with either combination significantly improved response rates and prolonged PFS compared with chlorambucil alone. These patients had a median PFS of about 2 years and an 82% risk reduction for progression or death. Obinutuzumab also significantly prolonged PFS compared with rituximab plus chlorambucil (hazard ratio, 0.39; 95% CI, 0.31-0.49; P < .001).