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: There have been a number of risk classification schemes developed for follicular lymphoma. The first of these was the FLIPI score (Follicular Lymphoma International Prognostic Index) based on nodes, LDH, age, stage, and hemoglobin levels. This was in the pre-rituximab era. And subsequently the F2, or FLIPI-2 was developed, which included some other features such as beta-2 microglobulin, the size of a lymph node, and bone marrow involvement. This has not been as widely adopted. We're having enough trouble remembering the first one, and along comes the second one. These include things that we mostly don't have any control over and can't target. You can't target a patient's age. You can't target their LDH level or their beta-2 microglobulin.
Very recently, Pastorian coworkers have published what's called the m7-FLIPI. They went through a number of genes—about 74 genes—that have been shown to be mutated frequently in patients with follicular lymphoma. And they developed a scoring system, which included 7 genes, along with the FLIPI score and performance status. And using those factors, putting them all together, they were able to develop a schema that better distinguished high-risk and low-risk patients. In fact, it took some of the FLIPI high-risk patients and made them low-risk patients. And they behaved like low-risk patients.
This is important because we have another scheme system here and who cares? But we do care because some of these genes may eventually be targetable and may provide another opportunity for a noncytotoxic approach to the treatment of patients with follicular lymphoma.
Richard R. Furman, MD: It certainly is always nice to know what the future holds. And, of course, that's just not possible with our patients. Certainly knowing when to intervene with a more toxic therapy, in order to have a better outcome, is very important. Right now, the risk stratification is predominantly based upon time-to-disease treatment, disease burden, all those things that are identified in the FLIPI and other scoring systems, which really measure tumor bulk.
I think that knowing a little bit more about the genetics in the future will help us identify those patients who really need to be treated differently. So, looking at genes like c-Myc and BCL-2 and BCL-6 and their interactions with the triple hit lymphomas, has taught us a tremendous amount of information regarding the aggressiveness of large cells. We will certainly find information similar to that in the follicular lymphoma patients.
Transcript Edited for Clarity