Friday, September 9, 2016

EFS12 (Event-Free Survival at 12 Months)

About a month ago,  two readers names Kevin and Tom had a conversation in the comments section. Kevin had some questions, and Tom had some very encouraging responses. (I really love to see that. As much as I enjoy hearing from readers that I am helping them, it's great to see people helping one another, too, and knowing that I played a small role to bring them together.)

In his response, Kevin said, "I was diagnosed in December 2014, and treated with B-R from January 2015.I was very motivated by a study published end of 2014, written by Maurer et al, dealing with Re-calibrating life expectancy after having an event free 12 month after diagnosis ( EFS12 )
Events here means no lymphoma progression, relapse, death, etc, not side effects of the treatment. That is really one of the most encouraging studies I have seen.
Maybe Bob has written about that earlier. otherwise Bob, I am sure many folks here would be delighted, if you could...:)"


How could I refuse a request with a smiley face at the end?

I looked back at posts from late 2014/early 2015, and I couldn't find anything about this study that I had written. It seemed familiar, though, so maybe I wrote about it when an earlier version was discussed at ASH or ASCO? I'm too busy to look any more, so I'll just write about it now. (I should look into getting some kind of a search function on the blog, too, to make this kind of thing easier to do, but I'm also too busy to do that.)

The article that Tom mentions is called "Event-Free Survival at 12 Months (EFS12) from Diagnosis Is a Robust Endpoint for Disease-Related Survival in Patients with Follicular Lymphoma in the Immunochemotherapy Era," and it was published in the journal Blood in late 2014.

The researchers were aware that some Follicular Lymphoma patients seem to better than others, and since Rituxan has been added to most treatments, Overall Survival numbers had been going up. However, they also knew that there was a smaller group of patients that seemed to have a more aggressive type of FL. Their goal was to figure out of they could tell which group was which, as soon as possible, to help figure out if aggressive treatment was needed or not.

They looked at a group of FL patients who were treated at the Mayo clinic over 10 years. Then they looked at a group of FL patients in Lyon, France, treated during roughly the same time period. they were especially interested in comparing Event-Free Survival (EFS) and Overall Survival (OS) -- if a patient didn't need treatment or didn't progress for a certain period of time (EFS), could that signal that they had a better chance at a longer OS? (And is the reverse true? Could a shorter EFS mean a short OS?)

They looked at almost 1000 patients with grade 1, 2, and 3a Follicular Lymphoma from the Mayo Clinic. (You probably all know that grade determines how aggressive the disease is, and 3a is closer to 2 than 3b, which is closer to an aggressive lymphoma than to an indolent lymphoma like FL. So we're basically looking at people who are less likely to have an aggressive type of FL, at least at diagnosis.)

EFS was measured from the time the patient was diagnosed, and the "events" that caused the timeline to stop included disease progression, relapse, re-treatment, or death due to any cause. They planned to measure EFS12 (how many patients did not have an event after 12 months) and EFS24 (no events after 24 months). Overall Survival (as always) involved death due to any cause, and was compared to the general population.

Overall, Follicular Lymphoma patients has a shorter Overall Survival than the general population, whether they had stage 1, 2, or 3a disease. However, when the 17% of patients who did not achieve EFS12 were taken out of the pool, there was no survival deficit. in other words, patients who went for 12 months without disease progression, relapse, re-treatment, or death had the same Overall Survival as their family, neighbors, and friends. The results were the same for the patients in the Lyon group -- those who achieved EFS12 had the same OS as the rest of the French population.

That's a pretty awesome finding, and Tom, as he said, is right to find it "very motivating."

Now, to be clear -- this study isn't guaranteeing that if things stay quiet for a year, you don't have anything to worry about. Statistically, it means your chances of a long OS are pretty good. But we are all individuals, and our diseases behave differently. Looking closer at the results, the follow-up on the patients was a median of 59 months, or 5 years, but the range was from 1 month to 131 months (about 11 years), and in that time, 43% of patients did have some kind of event, and 13% of patients died (that's from any cause, not necessarily from lymphoma). But the disease for most patients with an event after 12 months seems to have been of a type that it was treatable, and did not affect OS. (I'm counting myself in that group -- treated at 24 months, no treatment for the 80 or so months since then.)

So, yes, I think we can find some hope in this study. Follicular Lymphoma is such a strange disease for so many of us. We get a diagnosis and just wait for something bad to happen. Maybe this study can ease our minds just a little (though I think we'll always wait for that bad news).

Thanks to Tom for suggesting it (don't know how I missed it when it came out), to Kevin and Tom for having that conversation in the comments, and to all of you for reading.

Stay hopeful.

2 comments:

Anonymous said...

This rock star Dr. John P. Leonard seems to agree with this study (see link below).

“Most patients will not die from follicular lymphoma, and that's very reassuring. About 80% of patients will die with their follicular lymphoma and not of their follicular lymphoma,”

And keep in mind, this EFS12 study is a long term study. CAR-T very likely is the answer for the EFS12 (20%) and lets not forget the ol' standby SCT which has been around 20 years. SCTs today are much more successful than in the 90s. Both are curative options. A lot of the EFS12 may end up better off these days and may be cured instead of taking treatments periodically.

http://www.onclive.com/conference-coverage/hematology-2016/novel-agents-on-horizon-for-follicular-lymphoma

William May said...

Thank you for all the great fNHL posts Bob. In March 2016 my wife (who has aggressive fNHL) received a CAR-T infusion at NIH. She has been in complete remission for 6 months - our goal is EFS12 and longer. As Dr. Leonard said, we're hoping she will (way in the future) die with her fNHL and not from her fNHL.