Scott Huntington, MD, MPH, MSc: There are currently a number of unmet needs in follicular lymphoma in the relapsed setting. The greatest being what do we do for those patients who early relapse following standard immunochemotherapy? These are the 20% of patients who have early progression without large-cell transformation. There’s been a real shift to understanding that it’s unlikely that additional chemotherapy in that setting is the beneficial approach, and we’re incorporating earlier use of novel therapies in that highest-risk group.

There’s also an unmet need about patients who have a 7-, 8-, 9-year remission from the first-line therapy. What is that next-best treatment in second-line setting? Is it to use a similar immunochemotherapy approach, or should we be incorporating novel therapies?

Much like the first-line setting, where we need additional predictive and prognostic models, we need a similar approach and additional information to really help guide and personalize the medicine and the administration of therapy in the second-line setting.

One of the most important pieces of information before selecting a second-line therapy is what the patient received in the first line. Whether a patient received rituximab alone versus rituximab and chemotherapy, that is really the most critical first step to deciding on subsequent treatment.

The next is the duration of remission. If a patient achieved a remission in the first-line setting from immunochemotherapy that has lasted 5 to 10 years, perhaps going back to immunotherapy in the second-line setting would be in the patient’s best interest. If the patient had a nice remission to rituximab alone, it would also be a very reasonable and appropriate thing to rechallenge with rituximab upon progression as well. And knowing what they received in the first-line setting and the duration of response are really the 2 critical pieces hard to select in a second-line therapy.

A critical point in deciding what to do for someone in the second-line setting is assessing the response and how deep the response and how durable the response was in the first-line setting. We know from a number of trials now that early progression, typically within the first 2 years, portends an inferior outcome long term. Deciding if a patient has early progression and whether to treat them with a novel therapy or ideally on a clinical trial is key. I think we have less knowledge about what to do in those patients who had progressions, not quite 2 years but not quite 7 years, in that between area where there’s a lot of gray data on whether we should be rechallenging them with a different chemotherapy—if you had bendamustine switching to, say, a CHOP [cyclophosphamide, hydroxydaunorubicin hydrochloride, vincristine, prednisone]—based therapy, or whether we should be incorporating novel therapies in that patient population.

Transcript Edited for Clarity