Saturday, January 8, 2022

Managing Relapsed/Refractory Follicular Lymphoma

As I mentioned in my last post, the journal Haematalogica published a nice piece recently called "Prospects in the Management of Patients with Follicular Lymphoma Beyond First-Line Therapy." It's a nice summary of where we are and where we might be going. (And by "we," I mean those of us who have already had some kind of treatment.)

The article basically goes through the options that are available for patients who have already had a treatment, and whose FL has come back, or whose treatment failed. In the last 10 years or so, we've seen new treatments types become available -- PI3K inhibitors (Idelalisib, Copanlisib, and Umbralisib) , Immunomodulators (Lenalidomide), Epigenetic Therapies (tazemetostat), and CAR-T. Add these to the ones that were already available -- traditional chemotherapy (CHOP, Bendamustine, and CVP), Rituxan, radiation (for some stage 1 and 2 patients), RadioImmunoTherapy, and Stem Cell Transplants -- and you have a pretty good bunch of choices for FL patients.

One of the main points that the authors make is, despite all of these choices, there is still no clear Best Choice for R/R Follicular Lymphoma. It seems like all of our situations are just a little bit different from one another, and with so many choices, and so much incomplete data from clinical trials, it's impossible to handle it any way than to consider each patient's individual situation. and make a choice from the list.

(This is worth mentioning -- the authors say that "the flood of data derived from phase II studies, and the lack of randomized studies comparing treatment strategies" are part of the problem. There are so many new types of treatments that the FDA gives special consideration to many of them, allowing them to be used on patients even though they have only gone through a smaller phase 2 trial. The good thing is that they get to patients sooner; the bad thing is they don't come with the large amount of data that a phase 3 trial would bring. Same with the lack of "randomized studies." Clinical trials can be run in two basic ways -- give a bunch of patients the new treatment, or "randomize" the trial and give half the patients the new treatment and half an old treatment, and compare the two groups directly. Randomized trials are a little harder and more expensive to run, so they aren't used as often. Same deal as relying on phase 2 trials -- less information to use later on. So we have more treatments available to use in the last 10 years, since they got to us faster, but not as much information as we'd have if we'd spent 15 years on them. Nothing is easy with this disease.)

It's probably not worth going through every one of the available options. (I've pretty much been doing that for 14 years.) But there is a really cool-looking image in the article with many of the different treatments going after an FL cell, of you want to take a look.

I think it's more important to think about some of the other points the authors make about treatments for R/R FL patients.

One important point they make has to do with sequencing therapies. (It's important to remember that this is written by Lymphoma experts for other doctors.) For many of us, that first treatment won't be the last treatment, and neither will the second treatment. If that's the case -- we might live a long time, but those years will involve a bunch of treatments -- doctors need to think carefully about how side effects might build on the side effects of treatments that have come before. They might also need to consider things like "location and socioeconomics." Not every treatment is available at every cancer center, and even the expense of traveling for a couple of hours once a week might need to be considered. Not everyone can travel easily, and not everyone can afford to take a day off of work once a week, let alone being able to afford an expensive treatment itself. I like to think that doctors keep those things in mind, but it's good for them to be reminded of factors like that. 

And just as important, an treatment recommendations should "incorporate the patient’s goals." Some of us might be OK with taking a pill every day for a year or two (like with some inhibitors). Others might want to just "get it over with" and do all of the treatment at once (like with RIT). As patients, we have goals for how our lives will be lived. Doctors need to consider those goals. The "best" treatment isn't always the best treatment.

Which is related to the next point that the authors make -- Quality of Life matters, and needs to be preserved. If an FL patient has the potential to live for years with the disease, the treatment shouldn't cause such severe side effects that those many years are difficult. A treatment might offer the possibility of a cure, but with long-term side effects that case nerve damage of make the patients more vulnerable to infection. There needs to be an honest and careful conversation about that before a treatment is decided on.

Finally, the authors look to the future. Even as we have lots of good options available to us, there are still more on the way. (They mention bispecifics as an example.) There are also lots of combinations being studied. Sometimes, two treatments work together in ways that are better than the two individual treatments -- R-Squared is a good example.

The hope is that the newer treatments will mean fewer or less severe side effects, and longer times between treatments. We're learning more about the biology of FL, too -- more potential biomarkers, and more about the pathways that cancer cells take to live and grow. All of that knowledge may lead to better treatments.

There's a lot here to be hopeful about. The treatment options really have changed a lot in a pretty short amount of time -- even in the almost 14 years since I was diagnosed. The article isn't written to us patients in particular, but that lesson is definitely worth learning.

The other lesson here for patients is also important -- with so many options, it's important that we know what they are, and what the implications are for each of them. I don't think we need to know all of the science behind every treatment -- we're not doctors or researchers. But we should know which questions to ask, and we should insist that our doctors take the time to answer them and explain what we need to know. A very good place to start is to think about your goals -- what kind of life you hope to live after the treatment is successful. That's a good place to start, and a good doctor should be able to start a conversation from that point.

I'm looking forward to exploring more of this with you all this year.


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