The European Hematology Association just published its updated Follicular Lymphoma guidelines in the journal HemaSphere. The guidelines are pretty comprehensive. They include recommendations for diagnosis, staging, first treatment, second treatment, and treatments after relapse. But they also include information about survivorship, which is pretty nice.
The guidelines are slightly different, I think, from those in the United States. They also are based on very recent phase III clinical trial results. So they are about as up-to-date as you can find.
I'm not going to go through all of their recommendations. I think you should read them for yourself. Here's the link again. But there are a few things from the article that I find interesting and worth highlighting.
Before I go on, this is a very good time to remind you all that I am not a medical doctor. I'm not a cancer biologist. I’m just a Cancer Nerd -- a patient with a blog who likes to read a lot. What I write is not medical advice. The best person to talk to about your disease is your own oncologist. But I hope sharing some of this makes that conversation a little easier. That's always the goal here.
One thing that I really liked to see in the abstract was this: “The median overall survival at diagnosis now likely exceeds 20 years.” That's pretty remarkable. When I was diagnosed almost 19 years ago, the literature on FL put the median survival at 8 to 10 years. We've more than doubled it in that time. I'm going to write more about that soon.
But for now here are a few thoughts from EHA guidelines. First is diagnosis. The guidelines say that about 85% of FL patience have the t(14;18) gene mutation. There are other common mutations as well, but they don't recommend testing for them, because there still really isn't enough information about them to know if it's worth knowing that a patient has a KMT2D mutation, for example. I've said this before -- there's still lots of research that needs to be done on biomarkers for FL.
In their discussion about first treatments after diagnosis, the guidelines still recommend active surveillance (or watch and wait) for asymptomatic, low tumor burden disease. They also suggest straight Rituxan is acceptable, though this treatment does not increase Overall Survival when compared to watching and waiting.
I found this especially interesting: For patients who do need treatment, Iimmunochemotherapy is the recommendation. This could be Bendamustine or CHOP along with Rituxan or Obinutuzumab. I think it’s interesting because there is so much discussion these days about “moving on” from traditional chemotherapy. They do mention R-squared as an option for a first treatment, but looking at the research, they say the clinical trials for R-squared showed it was comparable to Immunochemotherapy but not better. The guidelines say that Rituxan (or Obinutuzumab) maintenance is an option after Immunochemotherapy. Research shows that maintenance therapy extended Progression-Free Survival, but it did not increase Overall Survival. Patients who are susceptible to infection should not receive maintenance since it lowers immunity.
As for treatment at relapse, the guidelines recognize that there are many choices. Patients with asymptomatic disease can go back to watching and waiting. But for those who need treatment, the guidelines recommend R-squared. They also recommend considering R-Squared plus either Tafasitamab or Epcoritamab. Both of these combinations showed better response rates and longer PFS then just R-squared.
For patients who progress within 24 months after immunochemotherapy, the so-called POD24 group, options include CAR-T, though CAR-T after Bendamustine may be less effective because the Bendmustine messes with the T cells that are needed for CAR-T. The guidelines mention Stem Cell Transplants, which are still used, but much less frequently than in the past. There are many more options these days.
For patients who need a third line of treatment, the guidelines suggest Bispecific Antibodies, CAR-T, Zanubrutinib, and R-squared combinations. While there are several versions of Bispecifics and of CAR-T, the guidelines don’t recommend any particular version of either. They all have strengths and weaknesses that need to be considered when dealing with each individual patient.
The last section is on Survivorship. If you've been reading the blog for the last few years, you know Survivorship is becoming more and more important to me. Survivorship is what happens after treatment it's “finished.” The guidelines point out that about 90% of FL patients have a response to their first treatment. Most patients should see their oncologist for two years after they are finished with treatment. After that, they can see the oncologist less often. Survivorship after treatment should focus on some common long-term side effects and issues, including infections, vaccinations, cardiovascular issues, secondary cancers, fatigue, and psychological well-being. I'm very glad they included that last one. I continue to believe that cancer patients’ and survivors’ mental health is greatly ignored. Other issues that FL patients have to deal with during Survivorship include employment, financial issues, and anxiety about the disease returning. All true, and I’m impressed tat they are acknowledged in the guidelines.
As I said, I really encourage you to look at the guidelines yourself. That's especially true if you live in Europe. These guidelines are a little different from what is often recommended in the United States. And it's important to remember, as the guidelines point out, that not every treatment is available or has been approved in every country in Europe. So these guidelines are just that -- guidelines. A conversation with your doctor that includes a discussion of your own goals for treatment, your overall health, your financial picture, and your emotional state is really important. Choosing a treatment should be more than just picking the treatment with the highest numbers. There's so much more to be considered.
I did find it very interesting to read these guidelines, and to think back about what was available to me 19 years ago. Guidelines like this are constantly evolving, as they should, because the treatment landscape is constantly evolving. I think it's really interesting that treatments like Bispecifics and CAR-T, which get so much attention here in the US, are not recommended until much later in the process here. I don't think that says something bad about the European Hematological Association. I think it says something more about the oncology journalism in the United States. Doctors get very excited about those treatments, with good reason. But it's good to see that in the real world, they are one (or two) of many different types of treatments.
And that's a good thing. We have lots of options. And as these guidelines show, we have lots of very smart people who look at the very big picture to help determine which treatments, and in which order, are likely to be most effective for us.
I also think it can be a bit overwhelming to look at all of these treatments available to us and wonder how we would ever choose which one to use. But thankfully we don't have to, and it's because of those smart people.
Remember, talk to your doctor. Have those conversations even before you need to.
More soon.
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