Folicular Lymphoma is Complex....

Recently, the annual Debates and Didactics in Hematology and Oncology conference was held in Sea Island, Georgia. it is sponsored by Emory University.

A couple of weeks ago, The ASCO Post reported on the conference, particularly the session from Dr. James Armitage of the University of Nebraska (he also serves as Editor-in-Chief for The ASCO Post).

One of the main points that Dr. Armitage made was that Follicular Lymphoma is a lot more complex than we used to think. The cells surrounding the lymphoma cells, according to Dr. Armitage, play a role in the Lymphoma's survival. This probably doesn't come as a surprise to any of us. If you've followed where FL treatments have been, and where they are heading, it's easy to see that, gradefor most of us, a single treatment from a single agent just isn't going to do the trick, at least not permanently. Researchers are learning more and more about what makes FL so complex, and trying combinations that will deal with the different parts of the disease that make it so complex.

So Dr. Armitage tries to review some of the different treatment options available. This isn't an article that's offering anything new. But that's OK by me. I like to stop every now and then and see a nice summary of where we are now. It helps understand where we might be going.

Dr. Armitage looks at some controversies that have been in the news in the last few years, like the whole Watch and Wait issue (which I vowed not to write about again unless there was something new to report).

He has nothing new to report.

(W & W is OK if the patient is asymptomatic or elderly, but observation has to be very careful -- no just forgetting about it. As if that was possible for most of us......)

He also looks at research on R-CHOP vs. R-CVP, but says R-CHOP vs. B-R is more important. Both are better options than R-CVP, though a German study found Bendamustine worked better than CHOP. However, a United States study found Bendamustine to be not as effective as the German study fund it to be. Still, though, both have their place, and both work well.

He also mentions R-Squared -- Rituxan + Revlimid (or Lenalidomide), which had great results in trials, though as more patients use it, it seems to be not quite as effective as we thought. But as we learn more, he thinks it could be as useful as R-CHOP and B-R.

So how to choose among these options? Dr. Armitage thinks a bunch of things need to be considered -- age, health, symptoms, comfort with certain side effects, etc.

But he seems very clear about one thing -- the goal of the treatment should be a Complete Response. He doesn't think it is valuable to treat just to make the patient feel better or push things off for a while. Complete Responses have a "huge survival advantage," according to the article. He also thinks relapses are very difficult on patients (I think he means emotionally difficult), so he aims for CR and uses Rituxan Maintenance, which may prolong Progression Free Survival (though not Overall Survival), giving patients more time between treatments.

That's an interesting perspective. And one that some other oncologists would probably disagree with. (I remember the Lymphoma specialist I saw soon after I was diagnosed told me, Put 12 Lymphoma specialists in a room, and they'll have 13 opinions.)

Which brings us back to the idea of how complex Follicular Lymphoma is.

The good news, as always, is that we have some options, and there are even more on the way.

Nice to remind ourselves about that.

My Oncologist Appointment

I had a four month check up with Dr. K, my oncologist, today.

Everything looks great.

This time, he did a blood test. He had skipped it last time because he says blood tests don't really show anything, so he does them every six months at the earliest. The blood test was fine -- no significant changes from December, the last time I had one.

He did a physical exam, poking around here and there, feeling for any nodes popping up. Again, no changes since the last time he felt me up.

Then he gave me a lecture about CT scans, and why I wouldn't be getting one -- NCCN guidelines have changed over time, and we used to do scans every 6 or 12 months, and now we know that frequent scans over a long time have a risk of causing a secondary cancer, etc. etc. I tried to interrupt him a few times to say I was OK with waiting a long time between scans, but I couldn't really stop him from talking.

The important thing is, my health is good.

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After my first appointment with Dr. K, I wrote about how much I had missed Dr. R, my old oncologist. We had a great relationship. We could joke and tease, and talk about current research, and even his secretary would show us pictures of her grandkids. It seems a little strange to say, but going to the oncologist was actually fun.

It's pretty clear that things just aren't going to be that way with Dr. K. It's just not his personality. And it's only been two visits, but it seems like the whole office is the same way.

The word that kept coming to me was efficient.  The whole office is efficient.

They aren't cold, or unfriendly, or bad in any way. It just seems like they are there to do a job, and they do it. The phlebotomist made small talk about her hobbies, but there wasn't a lot of interaction. Dr. K asked all the right questions about my summer, if I traveled, about my kids. But I don't know it any of it really sank in. I get the feeling he won't remember any of it next time I see him.

Which is fine. I'm lucky to be at a place with my cancer where I feel like I can go in for my half hour appointment, get my blood tested, learn that everything is OK, and come back in six months. I don't need a best friend.

If I was actively going through treatment, maybe I would feel differently, and I'd need more emotional support. Then again, maybe I would like the efficiency -- "This is what the guidelines say, and this is what we're going to do." Let someone else make the decisions.

I'll be honest -- my wife worries about this relationship with Dr. K. She worries that, if anything happened to me, and she needed to make decisions about my health, she would have a hard time trusting Dr. K.

It's funny how, even when things are going well, we find things to worry about. Cancer sucks. Follicular Lymphoma sucks in particular.

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But for now, we can put those worries aside. There's no sense in getting worked up about something that might not even happen. Like I've been doing for seven and a half years, I'll do my best to prepare for whatever possibilities might come down the road.

For now, I had a good check up today, and that's what matters. I'm going to have some ice cream to celebrate.

Follicular Lymphoma in Younger People

Hey all you youngsters -- diagnosed with Follicular Lymphoma before you were 40 years old -- the Annals of Oncology has some good news.

The median Overall Survival for younger patients is 24 years, and getting better.

Compare that to the median Overall Survival for FL patients, which, depending on the study, is anywhere from 8 to 15 years. That's a pretty good difference.

Of course, I was diagnosed about 6 months after I turned 40, so I'm not counted in this good news. (Which I am trying hard not be angry about.....)

 The study is part of a larger study of 1002 patients from four European Oncology Centers (Barcelona, Spain; Bellinzona, Switzerland; London, UK; and Novara, Italy) between 1985 to 2010. From there, they looked at 155 that were under 40.

They found that, after a median 10 year follow-up, they found the median OS to be 24 years. Keep in mind what "median" means -- half of the patients were below 24 years, and half were above it.

The study found some other things, too. Compared to older folks (over 40), the under 40's were less likely to have elevated LDH, high beta2-microglobulin, and high risk FLIPI scores (all signs of more aggressive disease). However, younger folks were more likely to have bone marrow involvement, bulky disease (larger nodes or infected organs), and disseminated lymphadenopathy (swollen nodes in several areas of the body) -- all of which are "bad," but not necessarily signs of aggressive disease.

Also compared to older folks, youngsters had a 10 year median OS of 81% (versus 51% for us older folks), and were more likely to have stable disease for longer.

Also, youngsters had longer Progression Free Survival and Cause Specific Survival if they were diagnosed within the last 20 years and have a low FLIPI score.

All of this is fantastic news.

With that in mind, here's some cold water: the conclusion to the study says " However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population."

OK, that last part kind of stinks. But I'll take it. The overall message here is that Survival rates are getting better, not just for young people, but for all of us. And while, right now, we still have a shorter life expectancy than other folks, it's getting better. I have great hope that in 15 years (when I hit that 24 year OS), the landscape for treating Follicular Lymphoma is going to be so much different , so much better than we have now, that people will look back on my blog and giggle ("He thought about CVP? Ha! Was he a caveman?"). That's how much more advanced we will be.

Lots of good news here. As I've said before, I hate numbers and statistics -- except when they tell me something I want to hear.

Happy Lymphoma Awareness Day!

September 15 is honored every year as World Lymphoma Awareness Day, a movement begun by the Lymphoma Coalition. This is a world-wide initiative, which makes sense, since the Lymphoma Coalition is made up of Lymphoma-related organizations from all over the globe.

It always seems a little strange to talk about lymphoma awareness here, since the people who read this blog are probably the most lymphoma-aware people ever. (Be honest -- how many of you have ever stared at your lymph nodes, certain that they were getting bigger before your eyes?)

It's the rest of world, though, that's need some educating. Sadly, that includes some doctors. Last year's Lymphoma Coalition global survey found that 62% of lymphoma patients had been misdiagnosed -- doctors thought at first that it was something other than lymphoma. Clearly, the world needs some better knowledge about lymphoma.

The Lymphoma Coalition has some suggestions on their web site for what you can do to raise awareness. It's easy to spread the word online -- look at you, you're online right now, reading this. I'll bet you're on Facebook, Twitter, Instagram, or some other social media, too. Share some statistics, graphics, links, information -- anything to get the word out.

You have a personal investment in this matter.

Also, have some ice cream tonight. You deserve it.

Blue Ribbons

Once again, my local New England-style agricultural fair is happening, and once again, my daughter and I entered various categories. I've seen this, in some ways, as part of my duty as a father -- encouraging her to test herself, live through a judging by others, and vow to do better next time.

Of course, writing it that way makes it sound like she doesn't do very well. That's not at all true -- she has won first place blue ribbons for her cupcake baking. cake decorating, clay sculpture, and jewelry making.

And I've done pretty well myself -- blue ribbons for two kinds of tomatoes and two kinds of muffins (plus some second and third place ribbons for other vegetable and for cupcakes). Not too bad.

But mostly, it's become a kind of barometer for my daughter -- a way to see where her head is. The first year we did this, she was 11, and she didn't take it very seriously. The second year, she spent all summer and did some really great stuff. The third year, she was a little busier, but still put in a great effort on a few entries, and did really well. This year? Well......

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Before we get to that, we need to discuss MY results. I'm the cancer patient, after all, and it's my blog, so I'm really the most important thing. Skip to the next section if you want the sentimental stuff about my daughter.

First, vegetables, especially tomatoes -- nothing. Not only no ribbons, but I didn't even enter anything. I couldn't even find five decent tomatoes to enter. Or any other vegetable. The garden wasn't horrible this year, but it all really slowed down about three weeks ago. No more cucumbers or eggplant at all. Tomatoes are kind of all over the place -- a few ripe, lots of green ones in various stages of growth. But I need five of each variety, and I couldn't even find five that were in good shape, the same size, the same color. The fair is a week later than usual, and that had something to do with it, as did the last month and a half being especially dry. I thought about entering some swiss chard, but even that had lots of bug holes in it. I'll eat it anyway, but it wasn't pretty enough for the fair, so I didn't bother. That's the price I pay for not using lymphoma-causing pesticides, I guess...

I also entered some bread & butter pickles, nice sweet and sour slices. Last year, the pickle judges were pretty harsh -- only two entries, and no one got a first place, the other entry got a second, no one got a third, and I got nothing. This year, two entries again, with no first or second place. But I got a third. (And the other entry got nothing. Those judges are really had to please.)

Baking -- my chocolate cupcakes got nothing. They were once again under-appreciated.  By my fudge won a second place ribbon, probably because I added some bourbon to it. Next time I'll add a little more and hope for better.

My big success, though? My jam. My strawberry got nothing, and I'm not surprised, since there are usually lots of entries. But my big success for the night? A blue ribbon for my blackberry jam. Woo hoo!

This jam is kind of special. I have a shade garden in the back of my yard, and for the last few years, some thorny sprouts have been coming up, and I've been pulling them. Last year, after i had shoulder surgery, I couldn't do any yard work, and those thorny sprouts just kept growing. And then flowering. And then bearing fruit. Turned out they were blackberries, probably left there by birds or squirrels a few years ago.  This year, knowing that we had blackberries, I just let them grow -- no extra water or fertilizer, just whatever happened. And we got a ton of blackberries, enough for cereal in the mornings and dessert in the evenings for a few weeks, plus a big batch of blackberry jam. And that jam won a blue ribbon. Very satisfying.

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And as for my daughter?

She certainly didn't put in the effort she has in years past. She still likes to sketch, but now it's portraits of her favorite bands. And she still likes to sculpt, but it's mostly sculptures of the members of her favorite bands. She entered a drawing she had done a while ago and got a second place ribbon for it. And she entered a small sculpture she had done a while ago, and got a third place.  Not a lot of effort, to be honest, and it showed.

The place she did put some effort was in her decorated cake. But, to be honest, even that wasn't a huge effort. But it came out great. The cake decorating theme was "super heroes," and she made a Super Grover cake (he's the alter ego of Grover from Sesame Street; he's a well-meaning but not very effective super hero). I knew she was going to do well when she dropped off the cake and everyone working at the fair squeeled with happiness.

Not only did she win a blue ribbon for decorated cakes, but she also won "Best in Class" for all baked items:



That's pretty dang good.

So what does all of this say about my girl?

Well, I think it says this:

I think she's ready to move on from this stuff. She didn't do anything extra for the sketch and the sculpture, and really, as great as that Super Grover cake is, she didn't have to work too hard to do it. That's not meant to be a brag (though as a father, I'm certainly capable of that).

But she's not the girl she was three or four years ago, when she spent all summer planning and creating all the things she'd enter in the fair.

And of course, I wouldn't want her to be the same girl. I wish she'd maybe take the ear buds out and come out of her room a little more often than she does, but she's in a place where I'm glad she is at -- pretty self-confident for a 14 year old girl, aware of what she can do (and, with this cake, do pretty easily), but also willing to take on some challenges. She started high school a few weeks ago, and that's a whole new world, too.

Will she enter the fair again next year? Hard to say. It will be her last year in the "junior" division, so she may try one more decorated cake or pair of earrings. But if not, that's OK. I'm proud of how far she's come in the last few years.
 
It might be time for both of us to move her out of the "junior" division.

Transformed Follicular Lymphoma's Cell of Origin

The most recent issue of Blood journal includes research on Transformed Follicular Lymphoma ("Cell-of-Origin of Transformed Follicular Lymphoma"). As the abstract says, we really don't know a whole lot about transformation -- not enough to predict who might transform. This article describes research that attempts to change all of that.

The researchers looked at samples from FL patients that had transformed, and some that had not, including some that they had samples from before and after their transformation. This allowed them to see changes in the cells, so they could determine what was different after transformation. They looked for known biomarkers -- elements of the cell that are present that signal something important.

What they found was that the biomarker IRF4 was a "predictor of early transformation." IRF4 stands for Interferon Regulatory Factor 4. The gene related to IRF4 does what its name says -- it helps regulate interferons, which are very cool signaling devices in cells. When a cell is attacked by an outsider, it releases interferons, which let other cells know that they should put up their defenses. When there is a problem with IRFs, interferons stop doing their jobs, and attackers are allowed to run wild.

So if there's a problem with an IRF, the body isn't stopping out-of-control cells from growing. Makes sense that it would play a role in transformation.

The research made several other important discoveries as well, including "composite histology predicting favorable prognosis." The abstract doesn't provide any more detail, and I haven't read the entire article, but composite histology indicates two types of cells. I assume this means both Follicular cells and  transformed cells, and having both (rather than only transformed) is better news for a patient.

It will be interesting to see where research goes from here. There's plenty of work being done on targeting translocated genes like IRF4, and stopping whatever process it is allowing to happen. IRF4 is a "known biomarker" (and has been known for quite a while), so I'm guessing there is research already being done. Looking forward to seeing how it relates to transformed Follicualr Lymphoma in particular.

R-Squared: Phase II Trial Success

I've seen reports and articles on a bunch of Follicular Lymphoma research in the past couple of weeks, and I'm very slowly getting around to reading it.

Up first: results from a phase two trial of Rituxan and Lenolidomide (also know as Revlimid, making this combination R + R, or R-squared).

The combo has been around for a few years, and there has been some excitement in the lymphoma community about it, based on early results from the trial. The Journal of Clinical Oncology spells out the details in "Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)."

(Before I get to those details, check out the link and look at the Lymphoma Rock Stars in the authors' list, including John Leonard, Myron Czuczman, and Bruce Cheson. Damn. You know you're a Cancer Nerd when you see the authors list on a medical journal article and you squeal like a 14 year old girl who has seen that 5 Seconds of Summer, One Direction, and Fall Out Boy are performing live on the Grammy Awards telecast. And I say that as the father of a music-loving 14 year old girl.....)

Anyway, as the article explains, the trial compared Revlimid/Lenolidomide on its own with Revlimid combined with Rituxan (the R-Squared). The trial involved 91 patients, roughly half of them receiving each of the treatments. Revlimid/Lenolidomide on its own resulted in a 53% Overall Response Rate (20% Complete Response), while the R-Squared combo had a 76% Overall Response Rate, with 39% achieving a Complete Response.

The Conclusion to the phase II trial is that the R-Squared combination was successful enough to justify a phase III trial, with a larger number of patients.

These results were first reported in 2012, and have finally been reviewed by other experts to show that the results are as good as they seem. This is one of a bunch of studies on Revlimid and R-Squared that are going on now (here's another one). We won't see results from the phase III trial for a while, but we've seen enough people with positive results to call this an unofficial success.

Looking forward to it being official.