POD24 in Follicular Lymphoma

Important research from the journal Blood. 

In the article called "Validation of POD24 as a Robust Early Clinical End Point of Poor Survival in FL from 5225 Patients on 13 Clinical Trials,"the authors confirm that POD24 is an important concept in Follicular Lymphoma.

POD24 stands for "Progression of Disease before 24 months." (It is sometimes called EFS24 -- Event-Free Survival before 24 months.) The idea is simple, but unfortunate -- for FL patients who have had immunochemotherapy (like Bendamustine + Rituxan, or R-CHOP), if the treatment is successful, but the disease returns within 24 months, their Overall Survival is much worse than for most FL patients. Specifically, the 5 year survival is about 50%, while the 5 year survival for other FL patients is about 90%. 

The concept of POD24 has been around for a few years. It first came out in the GALLIUM study (see the link for more). It's important to understand what POD24 means. There isn't necessarily something magical about 24 months. It's that, statistically, there seems to be a greater chance of lower survival at about that point. Like all statistics, the 24 month cut off is not a guarantee of anything. Patients who progress before that point might be just fine. (Remember the numbers are about medians -- half will do better and half will do worse.)

Also, the treatment -- immunochemotherapy -- doesn't necessarily affect whether or not a patient does well or poorly. Statistically, patients who have only Rituxan (like me) don't have POD24 problems the way immunochemo patients do. But this doesn't mean Rituxan is more effective than chemo. It means people who are given Rituxan are more likely to have a less aggressive disease than a patient whose doctor recommends chemo. 

My point is, this study confirms that POD24 is a real thing, and it looked at 5225 patients in 13 different clinical trials (not just the 1200 patients in the GALLIUM trial) to make sure. But my other point is this -- remember that statistics tell a story about a particular group of people at a particular point in the past. Everyone's situation is different.

The research didn't just confirm that POD24 is legitimate. It also tried to understand why it exists. The problem right now with POD24 is that, while it affects about 20% of FL patients, no one knows whether or not a patient will be POD24 until their disease progresses. What we need is something to tell us, as soon as diagnosis if possible, whether a patient is likely to progress before 24 months after immunochemotherapy.

And the researchers did find some possible clues. 

And remember -- think of these as trends, not guarantees. 

Patients who did not progress at 24 months were more likely to have "Patients without progression at 24 months at baseline had favorable performance status (PS), limited-stage (I/II) disease, low-risk FL International Prognostic Index (FLIPI) score, normal baseline hemoglobin, and normal baseline β₂ microglobulin (B2M) level."

Patients who did progress were more likely to be male, have a Performance status greater than or equal to 2, and have a high-risk FLIPI score (3-5).

Some of those things don't need an explanation like being male. But others probably do. I've written a lot about FLIPI before; you can read more about it here.  It's basically a measure of some particular traits in FL patients (like age and how many places in your body the lymphoma has shown up). A patient is given a score based on how many of the traits she possesses. A high score means higher risk. Performance Status is similar, in that it looks at certain traits in a cancer patient (not just an FL patient, but all cancer patients), and assigns a score. But PS looks at how well the patient can perform some every day activities. A PS of 0 (the best) means fully active with no restrictions, while a PS of 2 (the cut off for this study) means the patient is able to walk but usually not able to work. A 3 means confined to bed more than half of the time. (Read more about PS here.)

So, essentially, patients are more likely to do well after treatment when they are healthy, and less likely when they have health issues or have more advanced disease. That's an over-simplifiction (a big one), but it makes sense. 

And that's helpful, but it's not enough. The article I have been discussing was accompanied by another article, commenting on it. This one is called "POD24 in Follicular Lymphoma: Time to be 'Wise'," written by Dr. John Leonard. He makes a point that lots of expert commentators make -- we need to do a better job of predicting, right from diagnosis, which patients will likely be POD24, and take care of them right from the start. He talks briefly about a study being done that looks at some biomarkers that might help identify patients who are POD24. In other words, researchers are trying to specific features of the cancer cells, not just general traits about the patient, that could help show which patients are likely to progress before 24 months. That's what we need.

This is an important study, if only because it gets people talking about how important POD24 is for 20% of FL patients. I wish those researchers luck in finding some answers. There's a real lack of answers for most of us with FL.