Insights From:Bruce D. Cheson, MD, FACP, FAAAS, Georgetown University Hospital; Shuo Ma, MD, PhD, Northwestern University Feinberg School of Medicine; Richard R. Furman, MD, Weill Cornell Medical College
Shuo Ma, MD, PhD: Another area to pay attention to is novel monoclonal antibodies. So among those, obinutuzumab is being studied now in the lymphoma field. Obinutuzumab has been FDA approved for use in chronic lymphocytic leukemia in combination with chlorambucil. This is a novel anti-CD20 antibody that's a type II glyco-engineered antibody that increases the Fc binding affinity. Because of this modification, obinutuzumab does have stronger ADCC activity, thus leading to more efficient tumor-killing compared to rituximab.
In the CLL11 study that compared the combination of obinutuzumab with chlorambucil versus rituximab plus chlorambucil, the obinutuzumab combination showed prolonged progression-free survival, as well as improved response and quality of response, demonstrating that the novel modified anti-CD20 antibody is superior to rituximab.
In the lymphoma field, there is a study that's being reported at this ASH meeting regarding combing obinutuzumab with chemotherapy. So, at this ASH meeting there are updated reports of combining obinutuzumab with a chemotherapy backbone in follicular lymphoma.
Bruce D. Cheson, MD: The GADOLIN study was a very important, very exciting phase III trial conducted in rituximab refractory follicular lymphoma. The design was that patients received either bendamustine at a dose of 120 mg/m2 on days 1 and 2. Or, bendamustine at a dose of 90 mg/m2 on days 1 and 2, plus obinutuzumab. The combination arm was also followed by maintenance obinutuzumab.
And there were some interesting observations. The first, was there was no difference in overall response rate by the end of induction therapy. However, the primary endpoint was progression-free survival. And, it was significantly longer with the obinutuzumab, with a hazard ratio of 0.55, without much in the way of additional toxicities. And this study has the potential to alter how we approach patients in this context who did not receive bendamustine-rituximab as part of their initial treatment.
Obinutuzumab is an interesting monoclonal antibody, an anti-CD20. How it will fit into the overall management of follicular lymphoma remains to be seen. In a head-to-head comparison with rituximab in relapsed follicular lymphoma, there actually was no difference in efficacy, and this was recently published by Laurie Sehn and her colleagues.
But in the GADOLIN trial, adding it to bendamustine with maintenance had a marked improvement in progression-free survival, and we are waiting longer for follow-up to see what the implications are, and potentially, for a survival benefit. We're way too early for that.
While we're trying to figure that out, we are now combining obinutuzumab with other agents active in the treatment of follicular lymphoma, other than, bendamustine. Some of the newer targeted drugs—idelalisib, ibrutinib, venetoclax and others. So, it's a very exciting time where we have new targeted therapies that may be more effective for improving the outcome of patients with follicular lymphoma.
Transcript Edited for Clarity