Carla Casulo, MD: The evolution of prognostic scores in follicular lymphoma have been in the making for many years. There are several prognostic factors that we use. One of them is the FLIPI [Follicular Lymphoma International Prognostic Index], which was published many years ago now. That was a retrospective overview of many patients diagnosed with follicular lymphoma with an overall survival endpoint, and it characterized survival based on the number of factors that patients had. That’s one parameter that we use for prognostication in follicular lymphoma. It groups patients into high, low, and intermediate risk. The other one that we use is the FLIPI-2, which incorporates other factors, as well as beta-2 microglobulin and bone marrow involvement and bulky disease, in order to prognosticate patients on the basis of progression-free survival. Those are 2 very well-known, well-established prognostic markers that we use. However, they don’t necessarily help to guide treatment of patients. They just help you to understand how they’ll do in the future with the treatment that they receive.
IHC [immunohistochemistry] is something that we use to help understand what’s on the surface of the lymphoma cell. Follicular lymphoma, when you look at it under the microscope, is characterized by the expression of certain proteins, and that includes CD10, CD20, and BCL2 [B-cell lymphoma 2]. It’s a way for us to identify the cell, but it’s not really used in terms of prognostication.
FLIPI is the most-used prognostic score because it has all of the things that we test on patients— hemoglobin, stage, and age. If you use the FLIPI-2, you have to order additional testing that’s not always widely available. I think in standard of care, if you’re in Europe, you may use FLIPI-2 more often, but if you’re in the United States, you’re more likely to use FLIPI.
There’s a third prognostic factor that’s being looked at in terms of research, which is called the m7-FLIPI. That one was developed with a multicenter study that developed the retrospective prognostic score using the mutational status of several different genes in combination with performance status and FLIPI score. Again, that’s really used for research purposes, and it’s not part of our standard practice for widespread complications.
In general, follicular lymphoma outcomes are very good. Most patients can live for almost 20 years with the disease, and some of them can go very long periods without needing any treatment.
However, there’s a lot of variability within that overall prognosis, so patients can sometimes have early disease recurrence and some of them undergo transformation. Some of them are refractory to their treatment, and that puts them in a less favorable category, but generally speaking, most patients will do quite well with this disease.
In terms of risk assessment, it is performed using some of the prognostic factors that we talked about, FLIPI and FLIPI-2, but sometimes you don’t have all of that information at hand when you’re seeing a patient, or if it’s a referral. You risk assess on the basis of the patient’s performance status, if they’re newly diagnosed, their comorbidities, and whether they can tolerate certain treatments. If they’re relapsed, then you want to determine the time that has elapsed from their first diagnosis to when they had recurrent disease. All of those things go into your assessment of risk when you’re seeing the patient for the first time.
Alexey V. Danilov, MD, PhD: At this time, there is not a single prognostic factor that will identify those high-risk patients who progress within 24 months of diagnosis or initial therapy. However, several different factors have been identified in studies, and that typically includes more advanced stage disease, so a higher Ann Arbor Staging Classification stage, FLIPI score, LDH [lactate dehydrogenase], and beta-2 microglobulin. The latter 2 essentially identify more proliferative disease, or sicker patients who also have higher performance status by ECOG [Eastern Cooperative Oncology Group], meaning patients who are in not such good shape, possibly because of more proliferative disease with more involvement of different organs. Then there are some biologic prognostic factors. For example, m7-FLIPI has been identified as predictive of early progression, as well as the new 23-gene score. However, those have not necessarily been found in widespread use in clinical practice, so it’s still a work in progress.
Comorbidities have been shown to predict outcomes in many lymphomas, and that’s certainly intuitive. It’s difficult to conduct a comprehensive assessment of comorbidities in everyday clinical practice. There is one parameter, which we have been using in studies, called Cumulative Illness Rating Scale. That includes 14 organ systems that need to be comprehensively evaluated. As you can imagine, that’s pretty difficult to do in everyday practice, so some simpler tests, such as TUG test—Timed Up and Go—are used. You ask the patient to get up from a chair and walk 10 feet, and depending on how fast or slow they can do that, it can help you predict how they will do, what their performance status is, and what their comorbidities are. Typically, you would essentially go through patients’ comorbidities 1 by 1 and determine what kind of an impact they would have on your therapy choice and outcomes.
The predictive value of PET/CT [positron emission tomography/computed tomography] still remains somewhat investigational. There are certain publications out there that indicate that total metabolic tumor volume [TMTV] is predictive of outcomes and progression-free survival. It’s particularly predictive when this TMTV value is combined with a FLIPI-2 score, and then you can really separate patients into 3 different groups, with high, intermediate, and low risk. However, this still has not found widespread use in clinical practice because of certain technical requirements that are there to conduct this assessment