What We Know About Transformation

There have been a few articles published in the last month or so on Follicular Lymphoma that are pretty interesting, and I am slowly working my way through them, hoping to write about them soon. My plan was to tackle one of them today, but then I got a couple of comments from a long-time reader, Jeanne. I started to reply to one them in the comments section, and it got so long I decided I would just make it a regular blog post instead.

Before I get to that, I will show you just how long Jeanne has been reading. This is one of her comments to me: "i still remind my husband fl strikes the most handsome so just have to accept it , wishing you health and all the best cheers!!"

I made that joke about FL only striking the devastatingly handsome a very long time ago. I think it was when the actor/politician Fred Thompson revealed that he had a type of indolent NHL about 10 years ago. That's a loyal reader. Thanks, Jeanne! (For reading and reminding me of how handsome your husband and I are.)

Jeanne's other comment was about transformation. As I'm sure you all know, Transformation is the term for what happens when a slow-growing lymphoma (like FL) turns into a different type of lymphoma -- a more aggressive one like DLBCL. The rate that it happens is up for debate, depending on the study that looked at it. Some say as high as 50%. But most that I have seen recently put it at about 15%, maybe 20% at most.

Jeanne's comment was in response to something I had written about the ASH conference, a study that looked at Bendamustine and Rituxan (B-R) and its relationship to Transformation.

The study also looked at POD24 patients (or EFS24 patients -- different term for the same thing). POD24 means "Progression of Disease within 24 months." That is, it describes patients who have had Immunochemotherapy (usually B-R or R-CHOP or R-CVP, all combinations of Rituxan and chemo), and whose disease returned within 24 months after treatment. This group makes up about 20% of FL patients, and their prognosis has been worse than other FL patients. The study confirmed that POD24 patients have a poor prognosis, with a lower Overall Survival than non-POD24 FL patients. It also showed some overlap between Transformation and POD24 -- most POD24 patients in the study had transformed.

Now, Jeanne asked a few questions about this study (which is complicated -- I needed to reread it a couple of times before I started writing): "So its basically saying that most pts with pod24 treated with frontline BR have transformed? BR might be the culprit of transformation with pod24 pts ? I have high hopes for BR but this article is worrisome, also are there new findings with regards to transformation? Like prevention methods or drugs to counter transformation , thank you!"

OK, first question: Have most patients with POD24 also transformed?

Well, in this study, Yes, that seems to be true. But that doesn't mean the two things are the same.
Transformation involves slow-growing cancer cells turning into fast-growing ones. Some people transform within 24 months after having Immunochemotherapy. But some people transform years later, after taking only Rituxan, or even after watching and waiting, with no treatment at all. It's scary because it's unpredictable. Everything is moving nice and slow, and suddenly there are night sweats and nodes popping up everywhere. (I remember reading, long ago, that the risk of transformation is pretty much gone after 15 years, but I can't find that reference anywhere.)

POD24 describes a very specific set of patients. They have been given immunochemotherapy as a first treatment and then needed another treatment within 24 months. It's possible that they started off with B-R or R-CHOP because their doctor saw that their lymphoma was aggressive from the start. That's one way to think about the difference between POD24 and Transformation -- POD24 starts off aggressively, and Transformation turns into something aggressive later on. (Of course, someone can also have a slow-growing FL that wasn't diagnosed for years, so when it does transform, it seems sudden, but maybe wasn't.) So there is some overlap between the two: someone who had immunochemo then needs another treatment, and maybe they Transformed, or maybe they just had an aggressive form of FL that has stayed FL (but has also stayed aggressive).

So the answer is, some people who need re-treatment in 24 months have transformed, some are POD24, but (just to complicate this) some might not have even had immunochemo, so they don't officially belong to either group.

Second question: Is B-R the cause of transformation?
Answer: Definitely No.
B-R has become kind of the default choice for lots of oncologists when a patient needs treatment. There are still lots of choices (B-R, R-CHOP, R-CVP, watching and waiting, R-squared, stuff in trials). And the choices are really spread out -- I don't think any of them are used by more than about 30% of oncologists as a first choice. In this study, the patients were given B-R, and some of them transformed. If they did a similar study with another treatment, they'd probably find the same results. The treatment didn't cause the transformation, it just happened to be the group that they were studying. In fact, they say in the conclusion "The use of BR has not changed the rate of transformation compared with that seen after frontline R-CVP." The transformation rate didn't get better or worse with a different treatment. So don't be worried about B-R -- it's still a really good choice for treatment (though ask the oncologist if it's the best choice for your situation).

That brings us to the third question: are there new findings with regards to transformation? Like prevention methods or drugs to counter transformation?
I wish I could say Yes,  but I can't. What we know about transformation hasn't really changed much since I started paying attention to it. there doesn't seem to be any demographic group that's more or less likely to transform (age, sex, etc.). And there doesn't seem to be any treatment benefit, either (you are more or less likely to transform if you had R-CHOP, for example -- nothing there). And so far, no clear biomarkers (having a certain protein on your cancer cells, for example -- nothing there, either).

Like I said, it's scary because it's unpredictable.
the good news, though, is that researchers seem to be doing better at narrowing how many people are likely to transform. It was as high as 50% when I was diagnosed, but now it seems closer to 15% to 20%. Some studies put it less than 10%.  So the risk of it happening appears to be smaller. (That doesn't mean that fewer patients are transforming -- it means researchers are better at measuring it). It also seems like the Overall Survival rates are getting better -- patients are living longer after transformation.

So that's where we are. Still none of the answers that we wish we had, but overall, in better shape than we were 11 years ago when I was diagnosed.
In the meantime, I suggest trying not to worry about it, and doing what you are probably doing already -- paying close attention to your own body and discussing any changes with your doctor.

Thanks for reading, Jeanne (and thanks to the rest of you, too).