Treatment Approaches to Relapsed Refractory FL


Carla Casulo, MD: Patients with relapsed follicular lymphoma have a number of different therapeutic options. Fortunately, there’s a lot of research being done in this space, which makes it a very exciting time. Personally, I think that the decision of selecting therapy at the time of relapse should be put in context of when the relapse takes place. Given the research that we’ve done, if relapse happens within the first 2 years of diagnosis or treatment, that is associated with a very poor prognosis for patients. So, I think that those patients should be approached slightly differently, perhaps treated with a more aggressive therapy, put on a clinical trial, or considered for something else.

But for patients who have relapse of their follicular lymphoma after the 2-year time point, there are a number of different options. Idelalisib was recently approved for patients with relapsed and refractory follicular lymphoma. We also have obinutuzumab and bendamustine approved for patients with relapsed and refractory follicular lymphoma.

Nathan H. Fowler, MD: Probably one of the most difficult decision points in treating a patient with follicular lymphoma is when that patient comes with relapsed disease. Relapse can be very, very different in different patients. What I mean by that is patients with relapsed disease can sometimes present with very asymptomatic disease because it’s found by accident or on a CT scan. They can sometimes present with transformed disease, or they can sometimes present with threatened organ function or symptoms. Depending on the patient’s comorbid conditions, the patient’s age, as well as how the disease presents, those factors often influence the next line therapy. I’ll give you an example.

In a patient who is fairly asymptomatic and achieves a durable remission—and I say durable is 3 or more years—I often will go back to the induction regimen. For example, if patients received single-agent rituximab, I’ll just use rituximab again. If they received bendamustine-rituximab and they achieved a durable remission and they don’t have a lot of disease, I often will use single-agent rituximab.

In patients who present with symptomatic relapse or bulky relapse, oftentimes if the patient is healthy, I’ll go back to chemotherapy. That would mean if a patient received CHOP plus rituximab in the front line and they’re presenting with bulky disease or symptomatic disease, I’ll use bendamustine-rituximab. Or, vice versa, I’ll use CHOP [cyclophosphamide, doxorubicin, vincristine, and prednisone] if they received bendamustine-rituximab.

Regarding patients who progress early, it’s becoming clearer that these patients represent a group with an inferior prognosis. There are data from Carla Casulo’s LymphoCare trial that suggest patients who progress within 2 years of initial therapy tend to do worse, regardless of the salvage regimen. Unfortunately, there are no studies looking specifically at that group, but if you extrapolate data from several other trials—for example, trials with a drug such as idelalisib, a Pi3 kinase inhibitor—there are patients who will likely respond. In those studies, they did have patients who were refractory to prior therapy or were resistant to rituximab, and they saw responses in over 60% of patients. We also saw patients from the early bendamustine trials who were refractory to prior chemotherapy and responded, as well as patients from emerging treatments, like lenalidomide or lenalidomide-rituximab, who were refractory to prior regimens and responded to therapy.

The punchline of all that is that in patients who relapsed early, I would explore novel agents. This would mean targeted therapy or immunotherapy, because we still don’t know if moving to novel agents could potentially change the natural history of these patients who traditionally have a poor prognosis.

Transcript Edited for Clarity

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