Lead investigator, John Leonard, MD, reviews the phase 3 AUGMENT trial investigating lenalidomide plus rituximab for the treatment of relapsed/refractory follicular lymphoma.
Results from the phase 3 AUGMENT trial investigating lenalidomide plus rituximab for the treatment of relapsed/refractory follicular lymphoma were presented at the 60th ASH Annual Meeting & Exposition in San Diego, California.
Although rituximab is an FDA-approved single agent for the treatment of relapsed/refractory low-grade or follicular CD20-positive B-cell non-Hodgkin lymphoma, preclinical and clinical data have shown antilymphoma activity when administered in combination with lenalidomide, which is an immunomodulatory agent that has also demonstrated antilymphoma activity independently.
While on site at the conference, lead investigator John Leonard, MD, sat down with Rare Disease Report®(RDR®) to review the trial data and translate what it means for the potential combination therapy moving forward.
[Editor’s note: Transcript is slightly modified for readability.]
RDR®: What was the inspiration behind the phase 3 AUGMENT trial?
Leonard: “The AUGMENT trial is a trial in patients with relapsed and refractory follicular lymphoma. It is evaluating the drug lenalidomide in combination with rituximab versus rituximab alone.
The inspiration behind this study was the fact that rituximab is the standard therapy for relapsed and refractory follicular lymphoma. There were a number of different preclinical and clinical studies that suggested adding lenalidomide to rituximab could improve efficacy.
That led us, after various phase 2 trials, [which then led us to] conduct the phase 3 trial in order to really make a comparison of the 2 drugs versus the 1 drug.”
RDR®: What are the hallmarks you observed in the data?
Leonard: “The primary endpoint of the study was to determine if the combination—adding lenalidomide to rituximab—was more effective than rituximab plus placebo. The primary endpoint was focused on progression-free survival, and it was a very positive study.
The progression-free survival in the combination arm was over 39 months versus 14 months in the single agent arm. Clearly, we met that endpoint and showed that progression-free survival and efficacy, by that measure, were improved.”
RDR®: Were there any surprises or challenges that you encountered in the trial?
Leonard: “I don’t think there were really surprises form the standpoint that the preclinical and, particularly, the early clinical data suggested that there would be a benefit. There were some randomized phase 2 and other single-arm phase 2 trials that suggested that the doublet—so to speak—would be better.
I would say that I was slightly surprised that the toxicity profile was quite manageable, relative to the single agent. As you would expect, you always have a little bit more in the way of toxicity, but in my view, it was pretty well tolerated. I think the tradeoffs of the safety and efficacy seem pretty favorable.”
RDR®: What sets the lenalidomide/rituximab combination apart from other treatments for relapsed/refractory follicular lymphoma?
Leonard: “There is a substantial fraction of patients with recurrent antilymphoma that are treated with single agent rituximab. Alternate treatments include a variety of other agents—chemotherapy, antibody combinations, some other kinds of drugs like PI3 kinase inhibitors, and others—are approved for patients with recurrent follicular lymphoma and other antilymphomas in certain situations.
I think the difference here is that this is not a chemotherapy approach, and it has a different safety profile from some of those alternatives. To be able to have a nice efficacy profile in the context of what is a pretty manageable safety profile is useful for some patients.
RDR®: What are the next steps with the phase 3 data?
Leonard: “The next steps with lenalidomide are quite broad. Lenalidomide is active in a variety of different lymphoma subtypes. It’s approved for certain lymphoma subtypes already. I think that this will be an important new option for patients; I think there will be patients that are treated with this regimen.
There are a number of different studies that are going on using lenalidomide in combination with other approaches—other agents—that will show how we can improve outcomes with additional treatment combinations.