First-Line Treatment Options for Patients With Follicular Lymphoma


Sameh Gaballa, MD, and Matthew Lunning, DO, FACP, review the frontline treatment armamentarium available to patients with follicular lymphoma.


Sameh R. Gaballa, MD: How about we switch gears now and talk about management in the first line? Let me start by telling you my approach, and then we could see how you manage these patients. But at this time, at least in my practice, the patients who are obviously not having any symptoms with global disease…are the patients we typically would not jump to treatments right away. Observation is reasonable. For some patients, I sometimes recommend single-agent rituximab. We have the UK data, the watch and wait vs rituximab, either 4 weekly doses or followed by maintenance in low-bulk disease, asymptomatic patients. The time to next treatment was not surprisingly longer in the rituximab arms, but still the survival was the same. Although patients were disease free for a longer time, you have to remember that about a third of patients in the watch-and-wait approach still have not needed therapy at all. So that’s something to keep in mind, but some patients are not very comfortable with the watch and wait. Anxious patients want to feel that they have more control over the disease. For those patients, I would recommend simulation rituximab. But for the vast majority of patients, I typically would suggest watch and wait. In terms of first-line therapy, rituximab/bendamustine is certainly one of the common options for patients with symptomatic multi-disease. I reserve R-CHOP [rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone] treatment typically for people I suspect have transformation based on PET imaging or any clinical characteristics that suggest disease transformation. Rituximab/ lenalidomide is an option, although it’s not FDA approved. We have the relevant study that randomly assigned patients with lenalidomide/rituximab vs chemoimmunotherapy. It was technically a negative study because the study was designed as a superiority study and the R-squared one is not superior. Overall, if you look at the response rates and the PFS [progression-free survival], they looked very similar, although obviously, we cannot say it’s not inferior because the statistical plan was not designed to look for noninferiority. But if I get a patient who’s very uncomfortable, say, with chemoimmunotherapy approach, they want a nonchemotherapy approach, rituximab/lenalidomide is certainly one of the considerations. How do you manage those patients?

Matthew A. Lunning, DO, FACP: Very similarly. I’ve often tried to bucket my [patients with] follicular lymphoma into 4 kinds of segments or squares. The asymptomatic, low-burden patients—I agree with you. Active surveillance is a reasonable approach. I think based upon the data, we know that about 20% of those patients will never need therapy in the lifetime of their follicular lymphoma. We just can’t predict who those patients are. So it’s hard to do active surveillance if you don’t actively survey them. To your point about the low burden—[if patients] can’t get their pillow to the head at night knowing that they have follicular lymphoma, if that is impacting their quality of life, then I agree with you. I pull vitamin R [methylphenidate] off the shelf, give them 4 weekly doses, and then put it back on the shelf and know that we’ve done it. I think COVID-19 has decreased my enthusiasm for doing that. In those situations, it just takes time and a lot of visits and a lot of trust because a lot of times these patients are the cases that are found incidentally, right? When they’re going for a mammogram, for instance, and they see an actual lymph node on the mammogram, and it leads to an ultrasound guided biopsy. So those scenarios where we have to get the opportunity to have a longer discussion, I think those are 2 to 3 visits [and] discussions. Often what I’ll do in those situations is an interim scan at 6 months after the diagnosis just to have the discussion of velocity of change. This is more my practice than driven by a lot of data, but I think that it does help patients, and it helps me to understand what the pace of their disease is. Because there’s lead time bias, this 2-cm lymph node could have been 2 cm for 5 years, or it could have been 1 cm 1 month ago. While you can palpate it, I think that objectively having that [scan] 6 months from diagnosis can help ease the active surveillance train and allow it to shift gears into a little bit more of a stable mental state of what their follicular lymphoma is doing. The third bucket is those patients who are asymptomatic, but have GELF [Groupe d'Etude des Lymphomes Folliculaires]–related criteria. So you know that historically the GELF criteria have been there to not necessarily mandate therapy but at least start to have the discussion of where it’s reasonable to start to dip your toe into the chemoimmunotherapy realm. And that’s where R-squared, I feel, enters into the room, but you can’t always get it from an insurance standpoint. I’m more keen on BR [bendamustine/rituximab] over BO [bendamustine/obinutuzumab] in those situations, especially if I’m not going down the R-CHOP arm. Then to your point, symptomatic bulky disease, I’m asking myself the question of transformation or no transformation as a de novo aspect. And if the PET scan—I agree with you—looks concerning, but you’ve been throwing darts in them and you can’t get a large cell lymphoma, or you excised the hottest lymph node and it still comes back as grade 1/2 follicular lymphoma, I still may have the discussion about using R-CHOP. The other one is grade 3A. I’ve classically used R-CHOP in that scenario. I know it’s kind of a gray zone where unless they have peripheral neuropathy where I think bendamustine is going to be a problem, then I would give them BR, and I have done that. But my bias is to give follicular lymphoma grade 3A R-CHOP from that standpoint. I haven’t been doing maintenance as of late, regardless of response. I think that a PET CT at the end of induction therapy is probably the best predictor of time to next therapy or PFS. But I think that time to next therapy—while it’s the best end point, not everybody uses the same end points to give the next therapy, and I think that that can cloud that end point a little bit. But also, so can PFS, if you do monitoring 3, 6, 9, 12, 15, 18, 21, and 24 months. With CT scans, you’re probably going to catch more asymptomatic relapses than if you just do an end-of-treatment PET and say, “We'll do scans if you don’t feel well, if your labs change, or if I feel something on physical exam.” So a lot of these real-world data come with the caveats of how you monitor the disease after the end of their first therapy.

Transcript edited for clarity.

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