ASH: Why Do Some FL Patients Do Well with Only Rituxan?

We're on to another ASH preview. This one is for the presentation called "3500 Follicular Lymphoma Microenvironment Signatures Define Patients Subsets Obtaining Long Term Clinical Benefit after Single-Agent First-Line Anti-CD20 Immunotherapy." 

Two things to remind you of. First, I have been fortunate that, when I was diagnosed almost 14 years ago with Follicular Lymphoma, my disease was slow-growing enough that I was able to watch and wait (hold off on treatment) for two years. After that, I had six rounds of Rituxan. I haven't needed treatment since. 

Second, when I look at and write about presentations from ASH, I focus on the things that I find most interesting. For me, "interesting" might mean something that affects many of us. In this case, "interesting" means it affects me personally.

At my recent oncologist appointment, Dr. H said he was very pleased with how things were going (and why wouldn't he be?). And he said something that he has said before -- it was great that Dr. R had tried Rituxan, rather than something like CHOP, all those years ago. And that my experience might have us questioning the field's wisdom in first-line treatment. Maybe we don't need to rush to R-CHOP, or B-R, or R-squared. maybe trying just Rituxan will help a lot of people without a lot of the side effects. He also pointed out that we don't really know why just Rituxan on its own works for some people but not others.

And that's why this presentation is so interesting to me -- it's about research that tries to answer that question. It's personal for me.

As the researchers point out, Rituxan on its own does a better job of bringing on Progression Free Survival than just watching and waiting. But not as good as immunochemotherapy (like R-CHOP or B-R), though Rituxan by itself results in far fewer side effects. The question is, how does a doctor know which patients might benefit from just Rituxan, the way I have?

To try to answer that question, the researchers looked back at the records of 81 FL patients who who had received only Rituxan as their first treatment, and also looked biopsy samples to look for biomarkers in their microenvironment (that is, anything that they had in common like gene mutations that might explain why the Rituxan was successful for them). They followed up for a median of 9.5 years, and found that Overall Survival was 82%, and PFS was 35% (they lived a long time, but most had their FL return).

The analysis that they did for the microenvironment is pretty dense, and probably not something you want to know the details of (though if you do, the link to the presentation will give you those details). But they did indeed find some biomarkers. Genes involved in "chemokine-cytokine signaling, T-regulatory cells, natural-killer cell activity and interleukin-17 signaling" were present in patients who achieved a Complete Response. (These are all related to the immune system responses.) Also, another set of genes was associated with worse PFS, with one group (IL22RA2, CCL22, TNFRSF4, IL17RB, CCL19) having too much activity, and another gene (CD209) having not enough activity. At the same time, GELF criteria and FLIPI score were not associated with PFS.

(I've written about this before, including in my last post -- things like FLIPI are too general to really say anything about an individual patient.)

The conclusion is that relatively simple genetic test could help doctors figure out if just Rituxan would be effective for a certain patient as a first treatment. It could potentially save money and improve quality of life, if Rituxan on its own results in a long stretch of time before another treatment is needed.

The bigger lesson here is that biomarkers may help to determine which treatments could help FL patients, for all the same reasons. Ideally, a genetic test at diagnosis could help a doctor say "Given the biomarkers that we have, the patient should have treatment X, which will give the best chance of success."

But, as I said, ideally that's what would happen. There has been plenty of research on biomarkers in Follicular Lymphoma, some moderately successful, some less so. Even this research shows some promise, but it doesn't say "Yes! We found the answer!" It shows that there is an increased chance that Rituxan will work better for certain patients, but there's still no guarantee. Cancer is too complex for guarantees -- especially a cancer like Follicular Lymphoma.

But it's step in the right direction.