Looking Ahead in the Treatment of Follicular Lymphoma


Scott Huntington, MD, MPH, MSc: The greatest unmet needs in frontline follicular lymphoma are really to develop predictive tools to identify the patients for the right treatment. For the majority of patients, they do quite well with immunochemotherapy, but there’s likely a subset in that group that immunotherapy alone, rituximab or bivatuzumab single agent, might actually lead to very meaningful responses. So I think we need to identify where we might be able to de-escalate therapy in that group.

The next is really to identify the patients who are at greatest risk for progression beyond immunochemotherapy, that 20% of patients who have early progression of disease. We really need to focus our clinical research efforts our correlative studies to identify the patients at greatest risk for failure of our current standard of care, which is immunochemotherapy.

This has been an exciting ASH [American Society of Hematology Annual Meeting & Exposition]. There have been a number of new therapies that have been presented. Certainly, incorporating obinutuzumab with lenalidomide in the first-line setting looked quite compelling in terms of the overall response rate and the PFS [progression-free survival] rate. I think it will be warranted to look at and enroll in randomized trials going forward. There may be a role of antibody-drug conjugates—polatuzumab, anti-CD79 drug conjugate that looks like it may have activity in follicular lymphoma.

There’s also perhaps an ability to incorporate additional antibodies beyond anti-CD20s. Anti-CD19 antibodies look to have activity in follicular lymphoma, and there’s a role of going forward with those trials as well.

And then lastly, we’re moving toward an age of perhaps having more targeted therapies available for follicular lymphoma. There are data presented here about EZH2 inhibitors, and use of EZH2 inhibitors in either EZH2-mutant or wild type. There seems to be activity in both subsets. Incorporating that therapy alongside either chemotherapy or other novel backbones I think will be an important strategy going forward as well.

A number of new clinical trials have been published recently about using obinutuzumab or using lenalidomide or PI3K inhibitors. I think there’s a role of all that in our patients. I think we still need to identify the patients who will benefit greatest from those, and currently we don’t have those tools at our disposal. And so for community oncologists who may not be as many patients with lymphoma using immunotherapy with a chemotherapy backbone is actually a good choice for most patients.

I think the critical need is identifying those patients who do poorly with immunochemotherapy—those 20% or so of early progressors. And in that subset, really getting patients into clinical trials; to really help understand how best to treat those patients is the critical need. So there are lots of exciting developments, but at least for the short term, standard rituximab-based immunochemotherapy is still a reasonable option for the vast majority of patients with follicular lymphoma.

Transcript Edited for Clarity

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