The experimental antibody obinutuzumab proved significantly more effective than standard therapy for newly diagnosed patients with chronic lymphocytic leukemia who have coexisting medical conditions that prohibit more-aggressive therapy, according to a recent study.
The experimental antibody obinutuzumab (Genentech) proved significantly more effective than standard therapy for newly diagnosed patients with chronic lymphocytic leukemia (CLL) who have coexisting medical conditions that prohibit more-aggressive therapy, according to a recent study.
Researchers from Germany randomly assigned nearly 800 patients to receive the oral medication chlorambucil (Leukeran; GlaxoSmithKline), chlorambucil plus rituximab (Rituxan; Genentech), or chlorambucil plus the experimental antibody obinutuzumab (Gazyva; Genentech). Both rituximab and obinutuzumab are antibodies that bind to CD20, a protein expressed on the surface of normal mature B cells, as well as most B-cell lymphomas and CLL. However, obinutuzumab is glycosylated, giving it higher binding affinity.
Patients in the obinutuzumab arm fared significantly better, according to the study, published in The New England Journal of Medicine. They experienced nearly 27 months of progression-free survival, compared to 16 months for patients in the rituximab–chlorambucil arm, and 11 months for patients who received chlorambucil alone.
“Obinutuzumab plus chlorambucil gives a pretty impressive result,” says Lee Greenberger, PhD, chief scientific officer for The Leukemia & Lymphoma Society, which has supported some obinutuzumab research. “It's possible that obinutuzumab will basically just replace rituximab in this patient population.”
Like many biologics, obinutuzumab, which is infused, can cause “a pretty significant infusion reaction,” Greenberger says. However, fever, chills, and nausea, which are most likely to occur during the first rounds of therapy, are manageable for most patients, he adds.
The research clearly shows that obinutuzumab is superior to the fellow CD20 antibody rituximab, says John C. Byrd, MD, professor and director of the Division of Hematology in the Department of Medicine at The Ohio State University in Columbus.
“The obinutuzumab–chlorambucil study really shows for the first time that we can prolong survival by adding a targeted therapy to chemotherapy,” he says, “but I don't think we'll be using that approach long term.”
Other research, he notes, suggests that there are better first-line therapies, such as ibrutinib (Imbruvica), jointly marketed by Pharmacyclics of Sunnyvale, CA, and Janssen Biotech Inc. of Raritan, NJ.
“Obinutuzumab will have a place, but it's hard to say exactly what the place is,” he says.