Tuesday, January 5, 2016

Dr. Leonard's Top 10: m7-FLIPI

Lymphoma Rock Star Dr. John Leonard (of Weill Cornell Medical College) recently posted his Top 10 Lymphoma Abstracts from the ASH conference. Only one Follicular Lymphoma abstract made the list, and it wasn't one that caught my eye, so I'm adding it here.

In the Oncology Times article, Dr. Leonard says he looks for abstracts that are less focused on biology, and more on clinical practice -- not so much about new genetic discoveries, but more on how to treat patients now (or in the next few years). He also wants to start some conversation about which ASH abstracts are most important -- a goal that I certainly agree with.

Since he's looking at all of lymphoma, he has a lot to work with. If you have been following ASH and ASCO and other cancer meetings for the last few years, you know that CLL has been getting a lot of great stuff lately. And it seems like Hodgkin's Lymphoma and DLBCL have also been getting a lot of attention. There have been good things happening with Follicular Lymphoma, too, but not quite as many, or quite as exciting, as some other types of blood cancer.

And so, Dr. Leonard only includes one abstract that deals directly with FL. It's this one: "A Clinicogenetic Risk Model (m7-FLIPI) Prospectively Identifies One-Half of Patients with Early Disease Progression of Follicular Lymphoma after First-Line Immunochemotherapy."Interestingly, it isn't one that caught my eye as I was looking at abstracts to discuss. I think I overlooked it because the subject of the abstract (developing the m7-FLIPI scale) came up over the summer, so I didn't think there would be anything new presented at ASH.

But there was some new stuff, so I'm glad Dr. Leonard pointed it out. The ASH presentation doesn't focus on how the developed the m7-FLIPI model, but more on how it can be used to identify high-risk FL patients before they received treatment.

A quick review on FLIPI, the Follicular Lymphoma International Prognostic Index. FLIPI is often used to categorize patients for clinical trials by giving a general sense of whether they are low risk or high risk. It is sometimes used to help a doctor determine whether or not to use an aggressive or less aggressive form of treatment on a patient, but FLIPI is not really the best way of doing that, because the factors are very general (things like age and stage) that don't necessarily determine how a patient's FL is going to behave. (For more on FLIPI and FLIPI-2, a revised version on FLIPI, I suggest visiting Lymphomation's discussion of the topic.)

One of the things that makes m7-FLIPI much better at being used as a tool for individual patients is that added "m7" part. That stands for the "Mutated Seven," which would be an excellent name for a team of Marvel super heroes, but really stands for seven genes that affect Follicular Lymphoma when they become mutated. The m7-FLIPI takes those mutations into account, which makes it much more specific to the individual patient than the old FLIPI.

The ASH abstract that was flagged by Dr. Leonard involved looking at patients who were potentially high-risk. Recent research has shown that patients who had chemo and then relapsed within 2 years might actually be part of a subset of FL patients that need to be treated differently. The researchers here are hoping that the m7-FLIPI would help identify those patients early on -- not two years down the road when things have progressed.

In the end, the m7-FLIPI did a decent job, but not a perfect job, and the researchers conclude that the index needs to be refined even more. The abstract tells us something about FLIPI indexes, no matter which one gets used -- they aren't perfect in identifying how an individual patient's FL is going to behave. There's nothing new there. We've always been mystified by this disease. There's still no accurate way to tell if we have a less aggressive version, or if it might transform, or anything else. It's all still a crap shoot.

Still, the study gives us some reason to hope. In Dr. Leonard's words:
“We know that patients with follicular lymphoma who have progressed within two years of their front-line therapy have an unfavorable prognosis long term, whereas those who progress late than two years have a much more favorable prognosis.
“The question is, how can we identify these patients earlier and, potentially through clinical trials and hopefully in clinical practice, treat them differently?
“Using the m-7 FLIPI prognostic score plus some molecular markers may identify a group of patients who will progress relatively early after front-line immunochemotherapy. Identifying them in advance of treating them and waiting to see what happens is a positive step in that direction.”

And we all know that even a small positive step is a good thing.

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