The History of Follicular Lymphoma

A lot of what I hear about Follicular Lymphoma comes from Google. I have a Google Alert set for "Follicular Lymphoma," so every morning, I get an email with links to the FL-related articles that have appeared online over a few days.

Many of them have to do with investing in companies that make treatments for Follicular Lymphoma. There are a lot them. I take that as good news -- if people are writing this much about how much money can be made on FL treatments, then things must be looking up for us, right?

Sometimes they are nice articles from local newspapers or TV channels with stories about people with Follicular Lymphoma who are holding fundraisers or running marathons. They are always inspiring. (Occasionally something I have written for another website comes up. I won't lie -- I think it's really cool every time it happens.)

And then there are the links to medical journal articles, or reports about them in sites for oncologists. These are also usually inspiring. It's mostly how I keep up on the latest and greatest news about Follicular Lymphoma.

Which is why it was so strange when an article from a medical journal from 2007 came up in my email. Most of what I get is very current -- posted online in the last day or two. But this one was 13 years old. My guess is that the journal just posted it, or re-posted it to a new site. But I read it anyway, even though it was 13 years old, based on the title:

"Follicular Lymphoma: A Historical Overview," published in the journal Leukemia and Lymphoma.

This was published a little less than a year before I was diagnosed. I was curious about what the state of the field was at that time. And I've read enough medical journal articles to know that there was probably going to be a section that said, basically, "Here is the history -- where we've been -- and now I'm going to tell you where we think the field should go." And that's the interesting part -- did the authors predict the direction things went?

(Spoiler -- they didn't, not exactly, and I don't think anyone could have predicted how FL treatments have developed.)

Here's some early FL history -- Follicular Lymphoma was first identified in 1925 by  researchers in New York City. It was first named after them (Brill-Symmers Disease), and was considered benign. It was eventually discovered to be a type of lymphoma. This part is fascinating -- the first two patients with FL were 28 and 32 years old (much, much younger than the age most people are diagnosed with FL these days). They had radiation, and it gave them good results.

But here's the most important thing to come from the article -- Follicular Lymphoma was discovered in 1925. That means its 100th birthday is in five years. WE WILL HAVE A PARTY. You can be darn sure I will still be around in 5 years, and I expect all of you to be, too. I'm going to start planning soon. This Zoom stuff is nice, but I'm envisioning a big get-together, someplace nice, for anyone who can make it. Maybe a bunch of them, all around the world.  Weird thing to celebrate, but it's 2020 and that's where we are these days.

There are some other fascinating bits, too (like, in a study of patients diagnosed between 1917 and 1939, 20% died within 2 years of diagnosis, which seems too much of a coincidence when we know today about EFS24 -- about 20% of patients will relapse within 2 years after immunochemotherapy. It was also considered very rare in the Western Hemisphere for the first part of the century, much like it is considered rare in Asia and Africa these days. That could be something environmental, or it could just be that it was hard to diagnose).

More interesting to me is the section on treatments. As I said, this was published a year before I was diagnosed, so it's fascinating to see what was available at that time. The article mentions radiation (mostly useful for stage 1 and 2 disease); Chemotherapy (especially CHOP, CVP, and Fludarabine, which were pretty much the options presented to me -- no Bendmustine at that time. Interestingly, Interferon is mentioned, something that never really caught on in the United States (though I know is still popular in Europe). Also, watching and waiting is discussed under chemo, since there were some studies that compared the two. Bone Marrow or Stem Cell Transplants are also discussed, especially Allo transplants, though the potential problems are also brought up. And then there are targeted therapies, especially Rituxan. Rituxan had only been approved for 10 years, so the article is hopeful that R + chemo would result in a long-term Overall Survival benefit. There is also some discussion of RadioImmunoTherapy, and of vaccines, and of anti-bcl treatments.

All of this brings back memories for me, especially the excitement over RIT and vaccines that I felt 10 or so years ago, when I really started researching treatments.

And then the most fascinating part of all -- speculation about where treatments for FL were headed (in 2007). The authors got some things right, but, as I said, I don't think anyone could have predicted 13 years ago where we were headed, specifically.

The authors acknowledge that a better understanding of biology, especially genes, would lead to some new treatments. I'd say this is correct. The "pathway" treatments we have now -- all those inhibitors -- comes from this understanding. The authors also hoped this would lead to better diagnostic tools, though the jury is still out on this one. We're still looking for biomarkers to help predict EFS24 and transformation, but there's nothing definitive yet.

The authors also predict, correctly, that so many new possible treatments will mean carefully considering how to test them all. They suggest things like not always relying on randomized studies (where two equal groups are given two different treatments so a direct comparison can be made). Instead, we might do things like rely on surrogate markers (for example, if a group does well at 2 years, and still at 5 years, we can assume that 2 years will be enough). I'm not sure the field has done as good a job as had been hoped with coming up with better ways to run clinical trials and approve more treatments in a faster way. And maybe that's a good thing -- I'd rather have a solid treatment that is a big improvement on effectiveness and safety than a bunch of treatments that make only small improvements. (In my personal, remember-that-I'm-not-a-doctor opinion.)

The authors also spend a little time on transplants, and whether or not they will be worth the potential problems in 20 years. A good prediction -- transplants are still a valuable tool for many patients, but they seem to be less popular of a choice than they once were, as more targeted treatments with fewer side effects become approved.

Finally, the authors remind us that, in 2007, great improvements had been made in Overall Survival. In the first half of the century, the 5 year survival rate was about 47%. By 2007, it was about 80%. These days, it's about 88%. Still getting better.

So there's your history lesson for today. The big takeaway (besides that we need to start planning for that party in 2025) is that, even in the 12 years since I was diagnosed, researchers have made some big advances. I like to think that, in another 10mor 12 years, we'll have even more advances that we can't even imagine right now. (But some smart researcher probably has already started working on it.)

One last quote from the article: "This is an interesting time for those interested in lymphoma."

Still true, 13 years later.