Friday, July 22, 2016

Follicular Lymphoma Risk Model

This isn't "new," exactly, but it's kind of "official" now.

At the ASH conference last December, some researchers looked at what is now called the "m7-FLIPI" model, and what it means for clinical oncologists -- the good folks we see when we have an oncologist appointment. 

That research has been written up and published in the journal Blood, in the article "Clinicogenetic Risk Models Predict Early Progression of Follicular Lymphoma After First-Line Immunochemotherapy." That means it has now been peer-reviewed -- looked over by other experts -- and seen as good enough research to be accepted by all.

So what does the article say?

Well, they begin with the idea of POD24 -- Progression of Disease within 24 months after treatment. Researchers have found that POD24 is a good predictor of Overall Survival. That is, if a patient has had immunochemotherapy (Rituxan + Chemo), and then has the disease return (if there was a Complete Response) or get worse (if there was a Partial Response) within 24 months, then there is a good chance that their FL is more aggressive than the usual indolent version. It's not transformation, but something else -- maybe an entirely different type of FL.

The researchers has hoped that the m7-FLIPI model would help them identify that group (which could make up about 20% of Follicular Lymphoma patients). FLIPI indexes are often used in clinical trials to make sure the group of patients in the trial are roughly the same. They look at factors like age, number of lymph node areas involved, etc. to come up with a very general assessment of risk. In other words, a high or low FLIPI score means nothing for an individual patient -- it doesn't predict how long you will live or whether a particular treatment will work for you.

last summer, some researchers proposed the m7-FLIPI model. This takes the standard (and, again, very general) FLIPI model and adds seven gene mutations (EZH2, ARID1A, EP300, FOXO1, MEF2B, CREBBP, and CARD11, if you're interested in knowing), and looks at all of these factors to determine how likely someone is to have this potentially more aggressive version of FL.

The m7-FLIPI has the potential to be more accurate because it is (as the article title puts it) "clinicogenetic." It combines the clinical factors that an oncologist can see (age, stage, LDH level, etc.) with genetic factors that can be seen only through analysis of a patient's genes.

In the article, the researchers looked at two groups of patients and found that the m7-FLIPI did the best job of predicting POD24 -- patients who had problems within 2 years of having immunochemotherapy.

The m7-FLIPI isn't a perfect predictor, however. The researchers recommend more work be done to identify this group of 20% much earlier, so that initial treatment strategies can be developed before that 24 month period.

So how does this affect all of us? At the moment, it might affect those of us who do fall into that POD24 group. More aggressive treatment might be necessary than was thought a while ago.

But as far as our every day lives go, I'm going to recommend that nobody panic, especially if you were diagnosed recently, or had immunochemotherapy less than 2 years ago. The models are not perfect, and no model can predict our individual diseases -- not yet, anyway.

As always, I recommend you live your life as "normally" as a cancer patient can. Hug your loved ones a little more often and little bit longer. Make your small part of the world a little bit better. And if and when the time comes, be informed enough to be able to talk to your doctor in a way that lets you understand what she tells you, and that lets you ask the questions that you need answered.



12 comments:

Terrilyn McCormick said...

I'm interested in finding out if my FL has these gene mutations but not having a lot of luck. I go to Penn's Abramson Cancer Center so I'm at a major center but my onc doesn't seem to think this is of much value and their lab currently doesn't offer this panel. Curious if anyone has had this workup done?

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Anonymous said...

The timing of this post is amazing. My wife is a little over a year into maintenance therapy. Her blood numbers have been great. We reported for routine maintenance last week, and we were informed that her white blood cell count was low and her LDH number was high. She was immediately put on Neulasta shots and bloodwork was shipped to the lab for a FISH test. We are now on eggshells waiting for any results. We return for blood testing this morning to determine white blood cell count.

She responded extremely well to B-R treatment and had a complete response. It's always in the back of your mind, but we felt like life was getting back to normal. Now we are fearing that we can be part of the POD-24 group. The idea of a lesser prognosis is very frightening.

I just needed to tell our story. We are still in our forties and raising kids. It makes it that much harder. We are fearing the worst, but we are also hoping for the best. Hopefully, it's just a bump in the road.

Bob, thanks for the blog. It has, for the most part, been very uplifting. I hope I can return with better news. If not, we will have to fight the fight for round two.

Thanks,

Kevin

Lymphomaniac said...

Hi Kevin.
I'm happy to hear that your wife responded well to B-R, and less happy that you're still dealing with some issues. I'll only say this: even those who seem to be in the POD-24 group aren't always in a bad situation. Statistics can suggest something, but we are always, all of us, a statistical group of 1, so stats suggest possibilities, not absolutes. And even if/when treatment is needed again, you have lots of options. I feel for you as someone who was diagnosed at 40. Keep up hope, and please give us an update when you get one. We'll keep you in our thoughts.
Bob

Anonymous said...

Update: thanks for the reply and the encouraging words. We actually received some pretty good news this morning. The FISH/Flow test and bone marrow biopsy came back negative!! We are still part of the remission group!! Yes!! The doctor is still baffled as to the reason for the lower WBC count. He is suspecting that she is starting to react to the Rituxan. Unfortunately, we can't complete the final 5 rounds of maintenance therapy. We are just very thankful that remission seems to be continuing.

We are scheduled to do a CBC every week until the WBC has improved. We are scheduled for a follow-up appointment in 6 weeks. We are a little nervous about the possibility of not being able to use Rituxan again in the future. The doctor stated that we could use Obinutuzumab if it is needed (I think that was the drug). He stated that this drug has about the same effect. That was a little comforting.

It has been a very long and tiring couple weeks. Thanks for giving me a place to vent the other day. I appreciate the reply and the kind words. I hope things are going well for you and for your family. It's hard to believe that it is time to prep for another school year.

Thanks so much,

Kevin

Lymphomaniac said...

Kevin,
That's great news! I hope the WBC improves quickly. Could have been the Rituxan, but it could have been a whole bunch of other things, too.
And Obinutuzumab is a good option. Very similar to Rituxan -- it's also a monoclonal antibody, like Rituxan (also known as a "mab" -- those last three letters of the name confirm that; Rituxan is the brand name for rituximab). And like Rituxan, Obinutuzumab targets CD20, the protein on the surface of the cancer cells. The difference is that Rituxan was created from mouse cells, and Obinutuzumab was created from human cells, so some think Obinutuzumab is an improvement because it will mean fewer allergic reactions. And Obinutuzumab has been approved by the FDA for second-line treatment, after B-R, pretty much the situation your wife is in.
So, overall, it sounds like you're in a good situation, right now, and if you need another treatment.
Good luck to you all. Enjoy those last few weeks of summer with a little more peace of mind, and let us know how things are going.
Bob

Anyway,

Tom68 said...

Hi Kevin

Try to google "Late onset neutropenia", which can hapen during Rituxan use, and which pulls your granulocytes down. Highly likely its what your wife experiences.
I also had a B-R induction, and stopped myself after 4 Rituxan maintenance shots, after having seen consensus in medical community, that the overall survival is not changed by the Rituxan maintenance. But PFS is longer.

Congrats to your wife and you, and wishing you all the best from Switzerland.

Anonymous said...

Thanks Tom, that is definitely something that I will spend some time researching. Dr. G had mentioned that we seem to be a rare case, but that it in fact happens. We will see how those numbers rebound in the coming weeks and months. I was a little suspicious at first because her WBC had remained stable and in the 4.5 to 5.5 range for the first 7 maintenance infusions. We had quite a surprise when those numbers dropped like a rock. We are talking 1.6 at the lowest. She received a series of 3 Neupogen injections, but that only has brought us back to the 2.5 range.

I have seen the studies suggesting that maintenance does not improve the overall survival. We are at peace with the current decision. It is a little nerve wracking knowing that we aren't actively fighting. We take this fight one step at a time. We are hoping it is just a bump in a very long road.

Thanks for the suggestion. We also wish you the best and hope you have many, many years of good health.

Kevin

Tom68 said...

Hi Kevin

I felt much sympathy for you and your wife, because my wife and I are also in our forties and raising kids.
Also when calculating the timing of your wifes therapy, she must have started the therapy around end of 2014. 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...:) You know, you are so amazingly great in writing about those medical studies.
Here really I want to thank Bob for such a great blog also from the European continent.
Bob you are going global on the FL front !!

Best regards
Tom

Anonymous said...

Kevin - I had a late count crash. Apparently those with rheumatoid arthritis are also given Rituxin and this is discussed more in that literature than in the lymphoma literature. If I recall correctly the the counts usually recover within no more than around 180 days. I had abruptly gone from stable, although a bit low counts, to a white count of 0.5 and no neutrophils. The speculation is that more people have this than is documented simply because so many do not get their counts followed after primary nhl treatment has ended. Apparently in the arthritis community literature this is not considered a big deal with respect to anything long term. My counts took about 2 months to get back to their usual stable lower levels and it was 5 years before I actually had totally normal counts (I did not do maintenance). My late count crash was only discovered accidentally as we were going to do Zevlan since I had to end Rituxan bendamustine early due to liver and bone marrow damange. Because of that blood draw prior to a bone marrow biopsy is why it was even discovered to begin with.

Anonymous said...

Thank you all for your kind and informative responses. We are monitoring blood numbers very closely, and two weeks ago, we received very good news, as the WBC returned to normal. This was a very frightening experience, but we have comfort knowing that the lymphoma has not returned. We now only have the uncertainty as to whether we can use Rituxin in the future. That is a little unsettling. We ended maintenance 5 infusions short of completion. We have an appointment with Dr. G in 2 weeks and should have more clarification. In the meantime, we continue to enjoy our PFS. We are looking forward to hitting 24 months at Thanksgiving.

Thank you all for helping us through the first bump in the road. Bob, I can't thank you enough for the blog. This is my happy place when I am feeling down. I can't help but feel like we are all extended family.

Thanks,

Kevin

Lymphomaniac said...

That's great news, Kevin. I hope you have some reasons to be extra thankful in November.
And it does feel like family sometimes. I'm thankful for having all of you read and comment and make me feel useful.
Bob