Trends in Treatment and Survival in Follicular Lymphoma

The journal Leukemia recently published an article online called "Stage-specific trends in primary therapy and survival in follicular lymphoma: a nationwide population-based analysis in the Netherlands, 1989–2016." Unfortunately, I can only see the abstract (the paragraph summary that highlights what the authors think are the main ideas). But there's still some interesting things to see there.

The article looks at a very large group of Follicular Lymphoma patients -- 12,372 of them, who were diagnosed in the Netherlands between 1989 and 2016.

That's an interesting group -- it includes some who were diagnosed before Rituxan made its way to the Netherlands (which was 2003, according to the article, a few years after the U.S., in 1997). But, of course, it doesn't include patients who were diagnosed in the last few years, which I think is significant.

 The researchers were interested in primary therapy (the first treatment that patients received), and in Overall Survival. Given the large number, and the fairly large span of time they looked at (27 years), they also broke the data down into age groups (18-60 years old, 61-70 years old, and over 70), and time periods (1989-1995, 1996-2002, 2003-2008, and 2009-2016), and then looked at trends within those periods, and for those age groups.  

I'd love to see the full set of data, but the article is behind a pay wall, and I don't want to spend $10 to read it (though I might get free access to it a little later). Still, what the abstract says is pretty interesting anyway.

As far as primary therapy goes, one of the trends they noticed was that, for stage I patients, radiation has always been a very popular treatment. This makes sense -- because stage I disease is only present in one place in the body, very often a beam of radiation can reach it and get rid of it. That dosn't work as well with later stages.

For stage II, III, and IV, the trend they noticed was that starting chemotherapy within 12 months after diagnosis became less popular over time. They see this as showing that watch-and-wait was becoming more popular as time went on.  This is kind of interesting to me (especially as someone who watched and waited for two years). I don't know what trends are in different parts of the world, but there are a lot of oncologists in the U.S. who say we shouldn't watch and wait anymore, since there are so many options now for treatment, especially non-chemotherapy options. (The argument for watch and wait has always been that there were limited options, so it was best to hold off on using them until it was necessary.) 

I think it's kind of interesting that they say "before starting chemotherapy," specifically. This is where I'd love to see the full set of data. For much of that 27 year period, traditional chemo was really the only option. But I don't know if this study accounts for other first treatment options, like straight Rituxan, or RadioImmunoTherapy, or some newer inhibitors. I have no idea of those treatments are even available in the Netherlands, though I'm guessing they are, since they have had EU approval. But the wording is pretty interesting to me, none the less.

As far as survival trends go, the news is very good -- "Relative survival improved considerably over time." They say this is especially true since 2003 (thanks, Rituxan), and in older groups.

They look at five-year relative survival rates for this study. For the time period 2009 to 2016, the 5 year survival rate for stage I and II patients was 96% for the 18-60 year old group, 93% for the 61-70 group, and 92% for the 70+ group. The numbers are lower for stage III and IV patients, but still good -- 90%, 83%, and 68%.  

This makes sense; as patients get older, they are more likely to have co-morbidities -- other health issues that may impact their lymphoma, or may have nothing to do with their lymphoma. In other words, it's very important to remember what Overall Survival measures -- death by any cause (cancer, but also heart attack, getting hit by a bus, choking on food, whatever). As we age, we typically accumulate health issues. It doesn't necessarily mean the lymphoma is worse is older people. 

(Please read this post on Overall Survival if you're not sure what that statistic means, or if you need a refresher on how to read cancer statistics without being thrown into a panic -- especially you folks who have been recently diagnosed.)

It's noteworthy, though, that the numbers for the oldest group (over 70 years) is different in stage I and II patients (92% five year survival) and stage III and IV patients (68% five year survival). Remember, these numbers are measurements for 2009-2016. And this where I think that few years makes a difference.

The authors say "There remains, however, room for improvement among elderly stage III-IV FL patients." They're right, if you look at those statistics. But some of those patients in that 68% were diagnosed in 2009, 2010, 2011 -- the options available to them were so different from what we have today. (I know, as someone diagnosed in 2008, who pays attention to these things.) Someone with stage IV disease in 2009 was likely going to get CHOP chemotherapy, a treatment which does a great job, but has some nasty side effects, including potential damage to the heart. So a doctor who is deciding how to treat that patient, say a 72 year old with some health issues (pretty likely in a 72 year old) has to consider giving, perhaps, fewer rounds of the chemo (less effective, but also fewer side effects) or full chemo (more effective, but greater side effects that could harm someone who already has health issues). 

In other words, there are lots of reasons why that 70+ group has a lower survival rate. And, 10 years later, my guess is that some of those 72 year olds from 2009 would not get CHOP today. They'd get R-Squared, perhaps, or an inhibitor, something that is less taxing on the body and may extend their survival by a few years. 

The big lesson from this study, for me as a patient, is this -- it's interesting to look back at what happened in the past, because it's almost always going to show how much things have improved. We are so much better off now than we were 27 years ago, or even 10 years ago, with newer, better, and more treatments available. And even the best study that looks back on history (and this one is pretty good, looking at 2016) is still out of date. 

Care to guess how many treatments the FDA has approved for Follicualr Lymphoma since the beginning of 2016?

The answer is seven: 

Obinutuzuman + Bendamustine (2016), Rituxan Hycela (2017), Copanlisib (2017), Obinituzumab + Chemo + O Manintenance (2017), Duvelisib (2018), R-Squared (2019), and Tazemetostat (2020). 

And that doesn't count the CAR-T treatment for transformed FL, or any biosimilars for Rituxan.

Again, the point is -- history is interesting, but this study doesn't tell us everything we need to know. And as much as I'd like to see the full data for this study, what I really want to see is the historical study of patients from 2016 to 2026. Because it will be about 2030 then, and I'll be older and grayer but still saying the same thing -- "Interesting, but it doesn't account for the treatments that were approved last year!"

(I also assume that I won't have to type any more in 2030, and I can just use brain waves or whatever to write my blog.)

 Lots  to be hopeful about, folks. Lots.