First-Line Therapeutic Options in Follicular Lymphoma
Insights From:Bruce D. Cheson, MD, FACP, FAAAS, Georgetown University Hospital; Shuo Ma, MD, PhD, Northwestern University Feinberg School of Medicine; Richard R. Furman, MD, Weill Cornell Medical College
Bruce D. Cheson, MD: A number of factors could be taken into account in selecting frontline therapies for patients with follicular lymphoma who need to be treated: age, comorbidities, and, importantly, the suspicion that something else may be going on. For example, if a patient not only has enlarged lymph nodes, but has drenching night sweats, weight loss, and other features suggestive that there may be an aggressive transformation, and perhaps you can't biopsy an appropriate node to confirm that suspicion, that sort of patient I might start on R-CHOP.
Almost every other patient I start on the combination of bendamustine and rituximab, based on two randomized studies, one by the German StiL Group and the other being the BRIGHT study, a pharmaceutical-sponsored trial, both of them showing that bendamustine-rituximab was at least as good as R-CHOP but without some of the very bothersome toxicities. It is hopeful in the future that we will be able to develop noncytotoxic regimens. There are some of these in clinical trials right now, and these would be a great benefit to our patients.
Shuo Ma, MD, PhD: As I mentioned before, patients with a limited-stage follicular lymphoma—those are referring to stage I or a limited stage II disease—can be treated with radiation therapy alone. And there is a 50% to 60% chance of cure with radiation therapy alone. So that's the preferred treatment regimen for limited stage follicular lymphoma. Of course, some patients may choose to avoid radiation and consider treatment with either rituximab or rituximab/chemotherapy. That'll be similar to the advanced-stage follicular lymphoma. The curative potential is demonstrated with radiation therapy.
Richard R. Furman, MD: In determining the long-term therapeutic plan for the patient, it's always very important to figure on what's going to be the important endpoint. For most patients, it really is improving overall survival. There's certainly going to be patients where just palliating symptoms is more important. In general, with patients where improving overall survival is the goal, one can certainly sequence more benign therapies up front—so lenalidomide or rituximab or other novel BCR antagonists—knowing that these patients can often be rescued later with chemotherapy agents like bendamustine or other new agents currently being investigated.
The idea of using a bone marrow transplant in these patients is always an important consideration. I'm not a fan of an autologous stem cell transplant because of a risk of bone marrow failure and secondary myeloid neoplasia, and also a risk of transformation on patients exposed with autologous stem cell transplants. In young patients who are showing active disease, allogeneic transplants, I think, are a very good and viable option.
Bruce D. Cheson, MD: I don't refer patients for autologous transplantation as part of frontline therapy. In fact, there was a consensus statement published by the European Society for Blood and Marrow Transplantation, which also supported that this not be a treatment option in a front-line therapy. Perhaps it has a role later on in the course of the disease, but not as a consolidated frontline measure.
The topic of maintenance therapy with rituximab following initial induction treatment for follicular lymphoma is controversial. Personally, I use it infrequently. There are reasons for this. Every study that has looked at chemo-immunotherapy followed by maintenance or not has shown a prolongation of progression-free survival but no survival benefit, and with an increase in cost and an increase in toxicity. And when you don't have improved survival despite prolonged progression, it's most likely a reflection of salvage therapy.
And there have been a number of clinical trials such as the RESORT study in which patients were randomized to four weekly doses of rituximab and indefinite maintenance or retreatment upon progression. And although the progression-free survival was a bit longer, it was at the cost of 15 versus 4.5 median doses of rituximab. And the eventual outcome was exactly the same.
So, I don't do it personally. There are so many regimens. There is the SAKK regimen, which is one dose every two months, four times. Some do it every two months for two years, every three months for two years, four doses every six months, or indefinite. There isn't a uniformly accepted schedule of maintenance therapy.
Now, it is very popular in some areas, but personally for those reasons, I would rather reserve it for retreatment than put a patient through this prolonged treatment, increased expensed, increased toxicity, and increased nuisance.
Transcript Edited for Clarity