Upfront Therapy Strategies in Follicular Lymphoma



Ian W. Flinn, MD, PhD: Loretta, maybe you could discuss how you approach patients with the timing of therapy, perhaps what your first choices are in the treatment of patients with follicular lymphoma.

Loretta J. Nastoupil, MD: I think you raise a very valid point. It’s very challenging to have this discussion with patients in the clinic when you’re first meeting them and they have a newly diagnosed follicular lymphoma where you have to cover life expectancy, which, as been mentioned, is quite long. The variability in treatment options and the heterogeneity in terms of how people use these options is quite complex. So, it’s a difficult discussion to have. But I think it’s still important to note there are clear indicators for therapy. In academic settings, we typically apply the GELF criteria, which takes into account several factors, including tumor bulk symptoms, blood values in terms of LDH, and cytopenias.

But when you talk to community physicians and you explore practice patterns, that’s usually not uniformly used as an indicator for therapy. What we also learned from outcomes in community practices is that they’re generally very good. So, you can draw 2 conclusions. Despite having an agreed-upon gold standard of care, these patients generally do very well, and clinicians are applying their own characteristics or criteria for deciding which therapy to use and when to initiate that therapy. They’re good at choosing treatments, and indications for treatment, when applied across various patient characteristics.

Ian W. Flinn, MD, PhD: How about when you decide that a patient needs therapy. So, a patient has bulky disease, they’re obviously symptomatic, and maybe they’re getting some cytopenia. You’ve decided it’s time to treat rather than watch and wait anymore. Do you have a standard approach? Do you use one chemotherapy regimen, or are there a variety of ones? How do you make that decision?

Loretta J. Nastoupil, MD: That’s a great question, and no, I don’t have a standard approach that I apply to all patients. I think though we know that the median age of diagnosis is someone in the early 60s. We’ve all seen patients in their 40s, up until 80 years of age, and that comes with various comorbidities and performance statuses. We also apply those factors when we decide therapy. As been mentioned, there are biology factors that drive some of our treatment decisions, such as PET scans, LDH, Ki-67, and grading, though it’s still quite controversial.

We have seen practice patterns change over time as well. What I mean by that is R-CHOP tended to be the most commonly prescribed regimen a number of years ago, and that seems to be replaced currently by bendamustine and rituximab. Some of that is ease of use or comfort level with the varying side effects or toxicity profiles. We do have prospective data that can help guide some of those decisions. Things have gotten even more complex now that we’re also questioning the CD20 antibody that should be paired with chemotherapy. But in general, if you have a high tumor burden patient, chemotherapy plus immunotherapy is the most common approach. You may choose your chemotherapy backbone according to patient characteristics, including frailty or performance status. There will be other questions or discussions that we have in terms of the duration of therapy as well. I would like to add one point. As we still don’t have one therapy that cures patients with follicular lymphoma, a clinical trial is something that I always discuss with patients as well.

Ian W. Flinn, MD, PhD: Perfect. Anas, do you have anything to add to that in terms of first choice of therapy for patients with follicular lymphoma?

Anas Younes, MD: I think the good news is that we have choices. We have different options to tailor what’s appropriate treatment for which patient. So, I tend to prescribe R-CHOP for patients who are preferably young and have high SUV by PET scan or a questionable biopsy that may indicate transformation. For elderly patients, I tend to use BR [bendamustine and rituximab]. For fragile patients, I tend to use rituximab also. We have options, which is good.

Ian W. Flinn, MD, PhD: Loretta, there’s this new formulation of rituximab that’s given subcutaneously. Do you have any experience with that? What do you think?

Loretta J. Nastoupil, MD: As you probably know, the first dose we’re still giving intravenously. And for patients who do not have a grade 3 infusion reaction, it’s then appropriate to consider. The ease of use is something that’s clearly influencing our practice patterns in time. What I mean by that is we have tremendous wait times in our infusion center, given the volume of patients, and this is something that’s usually injected over 7 minutes and can be done in the clinic or an infusion center. What we’ve learned is that patients prefer this, and it may be because of the time spent in our office versus at home. We’ve not seen any local reactions, and the nurses who are administering this, though there was some training involved, are quite comfortable with administering it. Though we’ve all had great experience and longstanding outcomes with rituximab IV, I think this now provides another option that will decrease some of our wait times.

Ian W. Flinn, MD, PhD: Perfect. Anas, we’ve recently seen this publication. We’ve seen the presentations about the combination of obinutuzumab and bendamustine. What’s your take on this? Is everyone going to be using this as frontline therapy? What are your thoughts?

Anas Younes, MD: I think you’re referring to the GALLIUM study, which included 3 different regimens: CVP, CHOP, and bendamustine with rituximab or with obinutuzumab. The randomized trial showed that there is trend in favor of the obinutuzumab-based combination compared to rituximab, about a 7% difference in median PFS favoring obinutuzumab. However, there’s a trade-off of slightly increased toxicity when you add the obinutuzumab, especially in the setting with maintenance where you get prolonged exposure to both bendamustine and the anti-CD20 antibody, more with obinutuzumab than rituximab. So, I think we have to choose and, as I mentioned before, tailor recommendations based on our patients’ needs, performance statuses, and disease statuses. I think obinutuzumab plus chemotherapy can be used safely to some patients. I don’t think it’s going to be a blanket usage for all different indications. I would favor it with CHOP or CVP. I rarely use CVP, but I would favor it with CHOP more than bendamustine. I tend not to use it as maintenance if I don’t need to.

Ian W. Flinn, MD, PhD: Peter, do you agree? What are your thoughts?

Peter Martin, MD, MS: I agree 100% with Anas that it’s great we have all of these options. And I also agree that it’s hard to predict necessarily how people will interpret the data and how they’ll use it. Loretta made the point that people tend to do really well with whatever decisions physicians are making already. I think that this will just give us more options to help that along. I think the data are supportive that obinutuzumab does improve progression-free survival at the expense of some toxicity. And so, it’s a discussion to have with patients every time.

Transcript Edited for Clarity

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