Monday, December 8, 2014

ASH: Understanding Follicular Lymphoma

I've been writing about some of the abstracts for the ASH Meeting, looking ahead to it, but at this point, we're right in the middle of it. It started on Saturday and runs through tomorrow. And it's huge -- I read a brief article from someone who is not in the medical field who is attending with his wife, who is a hematologist. The writer was overwhelmed at how large the ASH meeting is. He says there are about 18,000 physicians and researchers there, plus another 9000 or so people who work for pharmaceutical, medcial supply, and other related companies. ASH is clearly a big deal.

I've been avoiding some of the more technical abstracts that don't have fairly immediate payoffs for patients. I like to focus on treatments, and other things that make me feel good and are easy to relate to my, and your, situations.

But there's a lot of really interesting stuff at ASH about the biology of Follicular Lymphoma -- how it all actually works. And of course, this is important, too, because none of those treatments would be here if we didn't know something about how Follicular Lymphoma cells behave and interact with their environment. The research on cancer has been pretty explosive over the last 10 years or so, with huge advances, compared to what we knew before then. It's no coincidence that the Human Genome Project announced in 2003 that it had mapped the human genome. Once we had the map, it got a lot easier to start exploring the terrain, and we're seeing the results now (and have been for a few years).

So I want to give a quick review of some of the more biology-heavy ASH presentations on Follicular Lymphoma this year. You Cancer Nerds might enjoy the links to the abstracts, but I think all of us can at least get a sense of how much we're coming to understand what makes Follicular Lymphoma work, and maybe how that can help researchers fight it:

  • In "Multiparameter Microscopy Analysis of the Follicular Lymphoma Microenvironment and Normal Germinal Centers: In Vivo evidence That Follicular Helper T Cells Form Synapses with Neoplastic B Cells and Are Associated with Proliferation and Expression of Activation Induced Cytidine Deaminase," researchers looked at Follicular Helper T Cells, and the role they play in Follicular Lymphoma. T Cells are part of everyone's immune system. The T Cells in this study play a role in activating B Cells (another important part of a normal immune system) and allowing them to multiply and attack invaders. However, when the T Cells are off target (they interact with the wrong thing), they might trigger mutations that lead to FL. So, good T Cell work = lots of good B Cells. Bad T Cell work = lots of bad B Cells. (And, in  case you forgot, Follicular Lymphoma is a B Cell cancer.) Understanding this process might lead to treatments that target the process and make it stop behaving badly.
  • The study "Intratumoral and Peripheral Blood T Cells Recognize Mutated Neo-Antigens in Follicular Lymphoma" is another look at T Cells and how they might fight Follicular Lymphoma.T Cells work by recognizing antigens -- stuff that isn't supposed to be in us. Antigens are matched up with antibodies, which fight them off. The fight is a lot easier if we already have an antibody that recognizes the antigen (which is why we get flue shots -- so we can build up some antibodies that will recognize the flue antigen if we get it). In this study, researchers wanted to figure out if T Cells could recognize FL cells as neo-antigens -- new invaders that need to have antibodies created to fight them. Indeed they do recognize them as neo-antigens. This means there could be personalized vaccines created, using manipulated T Cells to find those FL cells. It could also mean that other immunotherapies could be developed to help the body fight them off naturally.
  • "Genomic Diversity of Newly Diagnosed Follicular Lymphoma: A Pilot Investigation" tries to take a wider look at the genomic changes in Follicular Lymphoma, looking for new biomarkers that might indicate differences in various Follicular Lymphoma samples. In other words, we know that all FLs are not the same, and we know that the (14,18) chromosome switch is one way to identify Follicualr Lymphoma -- but are there some other ways to identify it? And can those ways tell us something about how the FL will behave? The answer is yes, and some of the biomarkers seem to predict whether an FL will be indolent or more aggressive. You can look at the abstract for more deatils, you big cancer nerd, you.
I really just wanted to give a quick sample of some of the more science-heavy work being presentde at ASH. There's a lot more than just this, but these few should give you a sense of how much more we're learning about Follicular Lymphoma, and how that new knowledge might translate into new treatments.

But all that is down the road a ways. Maybe in a few years, we'll see the phase 1 results of all of this good, important stuff.


Anonymous said...

Awesome stuff, Bob! Perhaps the most exciting thing I saw coming out of ASH is a follow-up on the Phase I study out of University of Pennsylvania - my alma mater :-) - pertaining to CAR-T therapy. It had some amazing results for pediatric leukemia patients, and this tidbit regarding relapsed/refractory FL patients: "In a separate study, CTL019 charted a 100% response rate and 80% complete response rate in 5 patients with follicular lymphoma..."

I'm glad to have such a slow growing disease - it makes me think that I could be the beneficiary of this kind of research one day.

Anonymous said...

Thank you for highlighting the important stuff out of ASH. Lot of positive advances in treatments to come. Hope that I can hang in there to benefit from these in the future. Bob I love to read your blog regularly it's something like reading the news daily. thanks.

Lymphomaniac said...

Thank you both. I do think we will benefit from all of this god stuff in the future. Maybe the fairly near future.