Infection Risk in FL Treatments

Interesting research published last week in the European Journal of Haematology. Not very happy, but important.

The article is called "High Risk of Infection in ‘Real-World’ Patients Receiving Ibrutinib, Idelalisib or Venetoclax for Mature B-cell Leukaemia/Lymphoma." 

The quick summary: what we know about a treatment's side effects comes from clinical trials. Once a treatment has been approved for a particular use, there seems to be less research on side effects, so what we know about them is what we learned from the trials. There might be more research on effectiveness that happens after the trials, but not a lot of side effects. 

And I understand that impulse. I have mentioned a bunch of times that I have to stop myself from focusing only on how effective a treatment is, and ignoring side effects. The numbers for effectiveness are more hopeful and happy. So I make sure to mention the side effects -- the "Adverse Events," as they are called in clinical trials. They're important. Effectiveness doesn't mean anything if a treatment does a lot of harm. As someone said to me once long ago, "You can put cancer cells in a test tube and add gasoline. The gasoline will kill the cancer cells, but do you really want to put gasoline into your body?" The point stuck with me.

So I find it very interesting when researchers go back and look at treatments after the clinical trials are all done. It's called "real world" research. A treatment might be approved based on the results of 500 patients in a phase 3 trial. And then maybe thousands more patients actually take the treatment, and the effectiveness and side effects don't match up exactly with what happened in the trial. Those 500 patients are an excellent sample, but not always completely accurate. 

And that's what this article is doing. It looks specifically at three treatments used for B Cell Lymphomas and Leukemias -- Ibrutinib, Idelalisib, and Venetoclax. And it found that patients had a greater risk of developing infections than the trial results suggested.

While these three particular treatments are used effectively for a bunch of different blood cancers, they have had mixed results for Follicular Lymphoma. Venetoclax and Ibrutinib have both been tried on their own for FL patients, and didn't do as good a job as they have done for other blood cancers like Chronic Lymphocytic Leukemia. But they do seem to work better as part of combinations (like the ViPOR combination of Venetoclax, Ibrutinib, Prednisone, Obinutuzumab, and Revlimid). 

Idelalisib is a different matter. It was given accelerated approval for Follicular Lymphoma based on phase 2 trial results, and then problems came up during the phase 3 trial that would confirm the smaller trials results. The company that makes Idelalisib withdrew the treatment from the market. The official reason was that they were having a hard time recruiting patients for the phase 3 trial due to Covid, but unofficially, it wasn't selling well, and the FDA was finding problems with other similar inhibitors. So to me, it's not a surprise that researchers would find more problems than the clinical trial found.

What this research found was that patients who received these three treatments developed infections at a greater rate than patients in the trials. In the small study (67 patients), 48% developed a severe infection. The median time to first infection was 5.4 months. All of that makes sense -- these treatments work by going after cancerous immune cells, but also normal immune cells, so patients are more prone to infections. 

More importantly, the researchers found that patients had more problems when they had high scores in ECOG (Eastern Cooperative Oncology Group) performance status and high CCI (Charlson Comorbidity Index) scores. Both of these tests are very common and also make sense, since they are based on traits that would show that  patient is more likely to have health problems. (You can learn more about ECOG scores here, and  CCI Scores here.)

The major point for me in all of this is to remember that all treatments have side effects, and if you're in the habit of reading about Lymphoma research (and that's probably a reason that you're here), you need to look at all of the results of research -- the bad stuff as well as the good stuff. And when it does come time to need treatment, and you have options, it's important to as the doctor about things like side effects. Quality of life matters -- maybe a less aggressive treatment with a shorter PFS is more important to you than a more aggressive one with a longer PFS, if the less aggressive one means fewer potential side effects. More questions to ask makes for a better experience.

More fun Lymphoma research coming soon. Take care of yourselves.