In the December issue of ASH Clinical News Lymphoma Program, Dr. John Leonard outlined an approach to treating follicular lymphoma with Dr. Jonathan W. Friedberg and Dr. Brad Kahl. Noting how improved diagnostic accuracy and novel therapeutic approaches for follicular lymphoma patients have led to overall survival rates that are now measured in decades instead of months or years, they call for a new paradigm in the clinical research that leads to the development of new therapies for follicular lymphoma.
Given these recent observations, it is clear that the vast majority of patients with FL have very prolonged overall survival and, given the asymptomatic and non-morbid nature of their disease, are at risk for over treatment. However, certain subsets of patients remain resistant to standard therapies and suffer significant morbidity and mortality from this disease.
We feel that the most important advances in FL moving forward will come from understanding the underlying “high-risk” FL biology – including the events leading to histologic transformation, a frequent cause of morbidity and mortality – and applying precision medicine approaches to this biologically defined subset. Large phase III trials enrolling unselected patients with advanced-stage FL that incorporate prolonged maintenance approaches or continuous treatment with expensive medications and that use PFS should be avoided. Even in the relapsed setting, maintenance therapy has been shown to improve PFS over observation after bendamustine treatment, as seen in the recently reported GADOLIN trial, but this observations is unlikely to translate ultimately to clinical benefit for an unselected group of patients.23
For the majority of patients with FL who will die with rather than from their disease – and who have survival length similar to their counterparts without lymphoma – it is appropriate to consider rethinking our therapeutic goals. Such patients may receive numerous treatments over many years, all of which may be associated with acute, chronic, or long-term toxicities. If the patient’s overall survival is not limited by the disease, then the objective of therapy should be to optimize his or her quality of life.