Hi, my name is Dr Andy Evens. I am Professor of Medicine at Robert Wood Johnson Medical School, Associate Director for Clinical Services and Director of the Lymphoma Program at the Rutgers Cancer Institute, and Medical Director of the RWJBarnabas Health Oncology Service Line.
I'm happy today to talk about a few recent key publications and data sets in the field of FL. There's one interesting scientific one, one interesting prognostication that also is a biomarker-based, and 2 recent clinical trials that we will discuss.
I'll first start with the prognostication. This article was entitled, "M7-FLIPI is not prognostic in FL patients with first-line rituximab chemo-free therapy." This was published in the British Journal of Hematology this past January 2020.
We know the M7-FLIPI has been a biomarker-based panel of genes that has been analyzed in combination with the clinical FLIPI score, and shown to be prognostic in patients with newly diagnosed FL. Admittedly, most of that data are in patients treated with chemotherapy platforms.
Just to mention some of the genes in the M7-FLIPI, include EZH2, MEF2B, EP300, FOXO1, CREBBP, CARD11, and ARID1A. Those in combination with clinical scores are able to prognosticate different survival groups.
We're still trying to understand how to use that. Can that be used, the M7-FLIPI, to guide therapeutics, or who should be treated with what? We're certainly not there yet.
As I alluded to, this was mainly in patients treated with chemotherapy, in particular with alkylator-based therapy. There is not as much data in terms of validation of the M7-FLIPI in patients with bendamustine-based platforms or chemotherapy-free platforms. That's what this article looked at.
The Nordic Lymphoma Group had performed 2 prior randomized clinical trials where patients had received rituximab, alone or with interferon. It wasn't a huge study, but it was 95 patients who had fresh frozen tissue available for sequencing.
They showed with a median follow-up of about 11 years, that 76% of patients were still alive. I'm sure a good portion of these were low tumor burden patients. That's also an important factor to consider.
The bottom line is they showed that at least, in toto, the M7-FLIPI clinical genetic model did not hold prognostic significance. They broke out individual genes. They did show that EZH2 were associated with a longer time to treatment failure and EP300 mutations as an individual gene were associated with a shorter time to treatment failure.
Really not surprising I would say that it's really hard to find one all-saying truth in terms of prognostication, whether it's clinical prognostication, especially once you start to integrate in mutations or gene expression, that obviously what type of patient and, moreover, the type of therapy that is used probably is going to influence that.
Hopefully, we'll get to a point where there may not be just one prognostic score with different genes that it may be dependent and have a different risk score dependent not only on the patients who are included in being studied, but also the treatment received. More to come on that.
The next one is a very important preclinical publication that was just published in Cancer Cell in May 2020. This was by the Melnick Laboratory out of Cornell. The title of this publication is, "Mutant EZH2 Induces a Pre-malignant Lymphoma Niche by Reprogramming the Immune Response."
I'm going to talk to us in generalities. This is a very sophisticated and important paper. Really looking at what causes FL, the most common question I get when meeting a new FL or any lymphoma patient for that matter is, of course, can you treat this and what's my prognosis? The next question always asked is, what caused this?
The honest answer we tell patients is, "I don't know." Of course, there are important hypotheses and thoughts. This is more information to help fill that knowledge gap. We know that FLs are slow growing, generally, indolent tumors that do contain extensive follicular dendritic cell networks.
Within that follicle, you have a conglomeration of clonal CD20 B cells. We also know, in a good amount, there are recurrent EZH2 gain-of-function mutations. Again, generally speaking, I'll talk through this very interesting paper.
What they show in this analysis, in this paper, is that EZH2 mutations initiated FL by attenuating the germinal center B cell requirement for T cell help, and also drove slow expansion of GC centrocytes that became dependent on follicular dendritic cells. In other words, T cell help was impaired and mutant EZH2 prevented induction of proliferative programs such as MYC.
At the end, really, they were able to show quite eloquently that EZH2 mutation fosters the malignant transformation by epigenetically reprogramming the B cells to form a particular immune niche that really reflects the characteristics of the disease of FL. I point you to that paper for obviously a much more detailed discussion of that important paper.
