Tuesday, January 27, 2015

Lymphoma Report Card

Well, once again, I'm looking at the calendar and realizing I haven't posted anything in a week. I've been reading a dense article on STAT6, which is a gene that seems to be very active in the kinds of processes that result in Follicular Lymphoma. That's the best I can do for you right now in describing it. Every time I try to sit down and focus on it, something else comes up. Blame it on new duties at work that are less predictable than what I was doing before. The next thing I know, a week has gone by and I haven't posted anything.

So I will ignore that article for now and turn to something else that's been sitting in my inbox for more than a week: The Lymphoma Coalition's Report Card for 2014.

The Lymphoma Coalition is an impressive organization made up of Lymphoma-related groups from around the world. There are several from the United States, including Patients Against Lymphoma (which runs Lymphomation.org), as well as the Leukemia and Lymphoma Society, Lymphoma Research Foundation, and others -- a total of 61 organizations from 45 countries. They share information about lymphoma with each other, and together serve as advocates for lymphoma research and awareness.

One of their big advocacy projects is their annual Lymphoma Report Card, which looks at data from around the world to help "tell the lymphoma story." Each year has a different focus -- in 2012, they focused on clinical trials and standards of care; in 2013, it highlighted the barriers that patients face. This year's report card focuses on treatments -- what is available, and who has access to those available treatments.

It's not exactly an uplifting report. I love to write about new treatments, whatever stage of development they are in -- pre-trial, phase III, in a clinician's hands, whatever. I try to be careful about reminding everyone that, as exciting as the results of a phase I trial might be, it could be a long time before we ever see that treatment being used, and there's always the possibility that it won't be used at all. But there's another warning that's necessary -- some available treatments just aren't accessible. Even though they have been approved, and shown to be effective, some are just too expensive or not well-known (or trusted) enough to get to the patients who need them. That's what the Report card highlights.

It's fascinating to me to see how so many different countries have access to certain treatments (like CHOP), but not to others (like Bendamustine or Ibrutinib), and which combinations are approved (some will allow Bendamustine on its own, but not with Rituxan, for example).

Some countries have clinical trials for pretty much every types of lymphoma, while some don't have any running for certain types (including Follicular Lymphoma -- in some countries, there is no new testing being done on newer FL treatments ).

Even worse, the statistics on physician awareness are not good. Lots of people are misdiagnosed at first, and given medication for conditions that have nothing to do with lymphoma. That's a problem no matter where you live.

Overall, the report calls access to care "sporadic," with lots of places around the world not able to provide diagnosis of lymphoma and proper care for patients, as well as access to trials. The Lymphoma Coalition is making an effort to address these issues.

And what can you do? Well, maybe this is the time to become a lymphoma advocate. As much as lymphoma-related organizations could use some of your money to help them spread their message locally, that's not always possible for patients. But I'm sure they could use your help in other ways -- by contacting the people who make decisions about lymphoma research and funding, and sharing your story.



Tuesday, January 20, 2015

Rituxan and Beyond

OncLive posted a piece yesterday called "Moving Beyond Targeted Therapy Stalwarts: Experts Weigh in on Four Tumor Types." The idea is that the first targeted therapies for some cancers have now been around for a while, and it would be interesting to see how far we've come, and where we might be going.

Of course, one of the "four tumor types" is Lymphoma, and the "targeted therapy stalwart" being discussed is Rituxan, which has now been with us for 18 years (having been approved by the FDA in 1997).

(I'm not going to quibble with the idea that Lymphoma is a single "tumor type."  We all know that there are as many as 60 different types of Lymphoma. The article doesn't say that exactly, but does discuss a bunch of different types of Lymphoma. Let's just move on.)

The expert doing the discussing is Dr. Andy Chen from the Oregon Health and Science University.

As I said, this doesn't focus exclusively on Follicular Lymphoma, but even the non-FL stuff is interesting, particularly because of some of the stuff I've been writing about here recently.

Some highlights for me:
The introduction of rituximab to the treatment of patients with non-Hodgkin lymphoma (NHL) in 1997 has doubled median survival to 10 years for individuals newly diagnosed with high-risk, low-grade follicular - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Knight Cancer Institute at Oregon Health & Science University (OHSU) in Portland - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
Moving Beyond Targeted Therapy Stalwarts: Experts Weigh In on Four Tumor Types - See more at: http://www.onclive.com/publications/Oncology-live/2015/January-2015/Moving-Beyond-Targeted-Therapy-Stalwarts-Experts-Weigh-In-on-Four-Tumor-Types#sthash.wQeQoXtM.dpuf
  • The article says, "The introduction of rituximab to the treatment of patients with non-Hodgkin lymphoma (NHL) in 1997 has doubled median survival to 10 years for individuals newly diagnosed with high-risk, low-grade follicular lymphoma." I think this is important to point out, because I read it three times before I really understood it. My first reaction was, "I think those numbers are low. Should it be "from 10 years to 20 years"? But then I read it slowly, and saw that the number was for "newly diagnosed with high-risk, low grade" FL. I think that's significant. We're not all considered "high risk," and that is measured by FLIPI or FLIPI2 scores. (See here for an explanation.) That's a particular sub-set of patients that has (as the name would suggest) a tougher form of Follicular Lymphoma than others. I don't know where that statistic (Rituxan doubles survival from 5 to 10 years) comes from, but it makes sense if we think in terms of high versus low risk. 
  • "In 2012, German researchers demonstrated that pairing bendamustine (Treanda) with rituximab significantly improved progression-free survival (PFS) over R-CHOP (69.5 months vs 31.2 months, respectively) as first-line therapy among patients with indolent NHL subtypes, including follicular lymphoma." Great news. However, as Dr. Chen points out, there is still the lack of an Overall Survival benefit to deal with (and that it's hard to measure because Overall Survival can go on for so long with Follicular Lymphoma patients). Not that anyone should be  complaining about increased PFS... 
  • And then there's the possibility of finding a monoclonal antibody to replace Rituxan. (18 years is a long time to be King of the MAB Hill.) One possibility is  obinutuzumab (Gazvya), which also targets CD20, like Rituxan. However, is was created using a process (called glycoengineering) that should make it more effective than Rituxan. It is already approved by the FDA for Chronic Lymphocytic Leukemia, and it is in a phase III trial comparing it to Rituxan in indolent lymphomas. We anxiously wait the results of that one.
  • A number of pathway targets have been approved (as we know), including Idelalisib/Zydelig. I found it interesting that these newer treatments have been more successful for indolent lymphomas like FL than for more aggressive lymphomas. I'm not sure why that's the case, but I find it interesting. Honestly, I don't pay a lot of attention to issues surrounding aggressive lymphomas, unless they are related to transformation. The article seems to suggest that treatments for aggressive lymphomas are not moving along as quickly as those for indolent lymphomas. I hope they make some progress for our brothers and sisters on the aggressive lymphoma side of things.
So, overall, there is some good stuff in the article. It's nice to see treatments talked about in comparison to Rituxan, which has been such a big help to us for so long.

Thursday, January 15, 2015

Lucky 7

Today is my 7 year diagnosiversary.  I was told, seven years ago today, that I had cancer.

It was not a good day.

Today is a much better day. But I had some serious doubts, seven years ago, that I would even be around to write this.


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For the last few days, I've been thinking about Stuart Scott. He was a personality on the all-sports television network ESPN, and he died on Sunday, January 4 from cancer at age 49. It wasn't lymphoma (not that it matters), and he'd been fighting it, on and off, since November 2007.

Maybe I've been thinking about him because he was diagnosed just a couple of months before I was.

Maybe I've been thinking about him because he was just a couple of years older than me, and his two kids were almost the same ages as my sons.

It isn't really Stuart Scott's death that I've been thinking about. I rarely think about death.

It's his life that matters.

He said as much in a speech. Last July, during the ESPYs, a sports award ceremony, he was given the Jimmy V Award for Perseverance. It is named after Jim Valvano, a college basketball coach who inspired millions, and who also inspired a foundation to raise money for cancer research, with a speech at the same awards ceremony 11 years earlier.

In his speech, Stuart Scott referred to something that Jimmy V had said in his speech, calling Jimmy V's words "the seven most poignant words ever uttered in any speech, anywhere: Don't give up. Don't ever give up."

[There's that magical number seven again.....]

In the days after Stuart Scott died, a lot of people quoted something else he said in his speech:

"When you die, it does not mean you lose to cancer. You beat cancer by how you live, why you live, and in the manner in which you live."

I think that's what I've been thinking most about for the last few days. Not death. I've been thinking about life. That's where our focus needs to be. How we live. Why we live. And the manner in which we live.

As I said, I saw lots of people quote those few words from Stuart Scott. But no one quoted what came right after, when he said:

"....So live. Live. Fight like hell. And when you get too tired to fight, then lay down, and rest, and let somebody else fight for you. That's also very, very important. I can't do this 'Don't give up' thing by myself."

That's the part everyone ignored, but maybe the part that's even more important.

Because if we hold up Stuart Scott and Jimmy V as heroes (and we should), as models for how to live with cancer, then we only see individuals. What we don't see is all of the people who support and help and love them. Those are the people that Stuart Scott spent the rest of his speech talking about: his doctors, his co-workers, his friends, his family.

I wouldn't have gotten this far without those people -- not physically or emotionally. No one does. So don't forget to thank all of those people, too.

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Seven is a great number. It's almost universally great, with lots of cultures giving it lucky or magical qualities. We use the phrase "lucky number seven." There are seven colors in a rainbow. The ancient Greeks had the Seven Sages. The ancient world had seven wonders. There are seven pillars of the House of Wisdom. There are seven corporal works of mercy, seven spiritual works of mercy, and seven virtues. There are seven Chakras. Seven gods of Good Fortune. The movie The Magnificent Seven had one of the best theme songs ever (though The Seven Samurai, the film it was based on, was even better). Harry Potter even wore number 7 for his Quidditch team. You can't get more magical than that.

So I have good feelings about this particular diagnosiversary.


And I think this is going to be a good year. I'll have a new oncologist soon. It looks like some fantastic treatments are in the pipeline. There will be lots to write about on Lympho Bob.

And, once again, thank you all for reading. I always say that I'd write this blog even if I was the only one reading it, but I'm glad to have you here, giving me some incentive.

(Oh, yeah -- I almost forgot. It's been seven years since I was diagnosed, but that means today is five years since I had my first Rituxan treatment. I guess that makes five a pretty magical number, too.)

Tuesday, January 13, 2015

Rituxan Maintenance -- Still Not Settled

The medical website Healio published an interesting piece a couple of days ago called "Robust Data Needed to Settle Maintenance Therapy Debate in Hematologic Malignancies." It's a little broader than a discussion about just Rituxan Maintenance in Follicular Lymphoma, looking at other maintenance treatments, and other blood-related issues, but what it has to say applies easily to R-Maintenance for FL.

(For those who don't know, maintenance therapy is the process of giving an additional treatment after a treatment has achieved a response, in an attempt to "maintain" that response. One common maintenance therapy for Follicular Lymphoma is Rituxan Maintenance -- after receiving R-CHOP and getting a response, the patient then gets Rituxan every six months for two years, with the idea that the Rituxan will clean up any left over FL cells that had been hiding.)

In a sense, it reviews (and doesn't necessarily add any new data to) the debate over whether R-Maintenance is worth it. Instead, the author, Dr. John Sweetenham, calls for some new research on the effectiveness of maintenance, and on how that effectiveness is measured.

It's a debate that's been going on for a while -- is maintenance therapy worth it? The studies that have attempted to answer that question (and Dr. Sweetenham refers to several of them) have not been able to give us a definite answer.

One problem is the way it has been measured. For the most part, researchers looking into maintenance have been measuring Progression Free Survival (PFS), or the amount of time it takes before the patient needs another treatment. Most studies show that R-Maintenance shows a PFS benefit -- that is, maintenance helps the patient go longer before another treatment is needed than would have been the case if there was no maintenance. However, most studies also show that R-Maintenance has no real effect on Overall Survival (OS). Dr. Sweetenham points out how difficult it is to decide between the two measurements. On the one hand, PFS isn't really the best measure, because most of us will probably need multiple treatments over time anyway. On the other hand, OS isn't really much better, and for the same reason -- if we need several different treatments over time, it's hard to say which one contributed most to OS. 

Dr. Sweetenham also points out that, as we shift our view of treating FL from looking for a cure to considering it a chronic disease, it is possible that we will be taking daily treatments -- maybe in the form of oral pills. If that's the case, the cost could be overwhelming to patients and to health care systems. (Imagine 40,000 Follicular Lymphoma patients each taking a pill every day that costs $100 each. The cost would likely go down, but maybe not as much as we'd like.)

Dr. Sweetenham's suggestion is that from here, studies on the effectiveness of maintenance also consider factors such as cost and cost effectiveness. In other words, while studies typically measure PFS and/or OS to answer the "is it worth it?" question, they should also consider whether a treatment justifies its potentially high price. If we need to justify it later on, having that kind of cost-effectiveness data will be very helpful.

All in all, this was a pretty thought-provoking article. (And for the record, Dr. Sweetenham would seem to be in the pro-maintenance camp, since he does prescribe it for his patients.)

I think what I like most about it is that it makes the assumption that Follicular Lymphoma is being seen as a chronic disease, that it is hard to measure its effectiveness because it is essentially chronic, and that the kinds of treatments that we will be focusing on in the future will treat it as such. It brings up some hard questions, but they are built on a foundation of hope.

Sunday, January 11, 2015

Numbers, Uncertainty, and Follicular Lymphoma

A couple of days ago, I posted a piece on Tony Iommi, lead guitarist for the band Black Sabbath, and current Follicular Lymphoma patient. I linked to a story about Iommi, in which he says, among other things, "I look at life differently now. I could be here another 10 years or just one year – I don’t know."


A few hours after I posted the piece, a reader named Rodrigo from Brazil posted a comment about the Iommi interview.  He said he felt sad reading that quote; he had some "old, terrible feelings" that came back.

So let me start by saying, Rodrigo, I'm sorry that something I wrote made you feel sad. I know it was Tony Iommi, and not me, who said that, but I linked to it. I did pull out the quote from Iommi about his nervously checking himself every day. I tried to put a positive spin on it, but it wasn't enough.

I don't ever want to make any of my readers sad. So again, Rodrigo, I apologize.

I've been mulling over Rodrigo's comment for a couple of days. And it brought some back "old, terrible feelings" of my own.

I think it's time to talk about numbers.

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I've said it a few times here: any time I've gotten really upset about being a Follicular Lymphoma patient, any time I've had those "terrible feelings," it has been because of numbers. I've told the story of going to see a lymphoma specialist a few days after I was diagnosed, and grabbing a brochure about FL from a rack, and seeing the 5 year survival rates. It sent me into a two-week depression, where I cried every half hour or so. That was the first time.

And for a while, I'd see numbers like that and think the worst. The survival rate is 75%, I would read. What if I'm one of the 25%?

 I think maybe it's that kind of number (10 years!) that affected Rodrigo so much.

Numbers are scary because they seem so certain. There's something objective and sure and specific about a number that makes it definite and hard to argue against. I remember a relative reading the Wikipedia page on Follicular Lymphoma a few days after I was diagnosed, and writing to my wife, "That number worries me: 8-10 year median survival." Yeah -- it scared me, too. Thanks for bringing it up.

The number is scary because it is concrete. It gives us something to hold on to when so much else is uncertain. And not in a good way.

But here's the deal:

Numbers don't really mean much, of all kinds of reasons.

Take, for example, that 8-10 year median overall survival statistic from Wikipedia. For a long time, that was the survival statistic that people quoted. At this point, it's based on some very old data (as an anonymous commenter pointed out in responding to and supporting Rodrigo -- thank you for the comment, by the way). The 8-10 years was based on survival statistics from patients who were diagnosed before Rituxan even existed. Just that one treatment, Rituxan, has changed the way we think about survival in Follicular Lymphoma.

And then there's the "median" issue. If you know statistics, you know that "median" is the exact middle point of a group. In other words, half of the people in a group are below that number, and half are about. So half of FL patients will survive less than 10 years, but half will survive more than 10. It could be 11. Or 15. Or 50.

So let's look at that half that survives less than 10 years, because that sounds scary. But it shouldn't be.

First of, let's remember that for many patients, FL is diagnosed at age 65 and above. That's far more typical than the young age that Rodrigo and I were diagnosed at. Again, it could be 65, or 70, or 75. Let's consider a 75 year old man diagnosed with FL. 8-10 years isn't such a bad thing for him, is it? That puts him at roughly the life expectancy for a male in the United States. So, really, FL hasn't affected him, statistically, at all.

And let's consider what "survival" means. The 8-10 year statistic measures "Overall Survival." That means it measures death from anything -- cancer, sure, but also heart attacks, snake bites, getting hit by trains, and any other possible cause. It doesn't measure only death from Follicular Lymphoma or something related to it.

So 8-10 years sure as heck doesn't mean that someone diagnosed with FL will die in 8-10 years.

No go back and read all of that again, but substitute "18-20 years," because that's probably closer to the Overall Survival these days, given the treatments we have available. (Again, thank you Anonymous commenter.)

And now throw that away, because it doesn't even consider the treatments that are in the pipeline, or that haven't even been thought up yet that might be available in a few years, thanks to accelerated approvals.

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It sounds like Rodrigo pulled himself out of his funk pretty quickly, and I'm happy for that.

And I totally understand why numbers can put us in a funk in the first place.

But I hope everyone remembers to take a step back when those old feelings start to creep up on them, and remember that numbers don't tell the whole story, and that as certain as they might seem, numbers really do a lousy job of telling the past, let alone telling the future.

Thanks again for reading.



Friday, January 9, 2015

Lymphoma Rock Star Update

If you read regularly, you know I like to call certain Follicular Lymphoma-related folks "Lymphoma Rock Stars." Sometimes they are great doctors like Bruce Cheson; sometimes they are patients like Betsy de Parry, who advocate for others patients.

And sometimes they are actual rock stars.

About three years ago, Tony Iommi was diagnosed with Follicular Lymphoma. Iommi was and is lead guitarist for the band Black Sabbath, and on his three-year diagnosiversary, he is talking about his cancer battle.

I was a Black Sabbath fan growing up (which helps explain my dwindling ability to hear as I get older), and I adored Iommi's opening guitar riff to "Iron Man." (Though, to be honest, once Ozzy Osbourne left Sabbath, my guitar loyalty shifted to Ozzy's new guy, Randy Rhoades. It's funny how things change -- when I was 18, I probably could have written 1000 blog posts on metal guitarists and their bands. I think that would have been more fun than writing about cancer, to be honest...)

Anyway, I was a Black Sabbath fan growing up, and so the headlines about Iommi getting lymphoma really caught my eye. He was about to begin recording a new album with Sabbath when he found a lump in his groin, which was eventually diagnosed. In 2012, it was announced that he had "early stage lymphoma," with no other details.

In how most recent comments, he reveals that it was Follicular Lymphoma that he was diagnosed with. He was going to ignore that lump, but Ozzy Osbourne convinced him to get it looked at. And when Ozzy thinks you have a health problem, then you really can't ignore it.

What really struck me, though, was the fear that he still has. It's something all of us can relate to. He says, "Every day I feel around for lumps and bumps. Every time I get a pain in my stomach I think, ‘Oh God, it’s cancer.’ It’s horrible." I think we've all been there -- and maybe we're still there.

For me, though, at some point that I don't remember, that "feeling every day for lumps" was able to stop. I don't think I've ever gone a day without thinking about cancer -- this blog and my daily check-in with the support group make sure of that. But at some point, I stopped obsessing over my cancer. I am at the point where I don't call my oncologist when I feel a lump or a bump or I have a strange feeling. My policy now is to wait three days, and if I'm still worried, I'll make the call.

I haven't called in a long time.


The other thing that struck me about Iommi's most recent comments was this: He's back on tour with Black Sabbath. He says, "Sometimes I wonder if I should try to live a more peaceful life. Then I think, ‘I don’t want to let the illness take over’. After all, I enjoy where I’m at now."

And I remember those days, too, saying No to a lot of things, wondering if I'd be around to finish whatever I started. And again, one day I decided that no doing things just didn't make sense. If I kept up with that same attitude, I'd end up never getting out of bed. I say no to lots of things now, but never because of cancer.
 
I know a lot of you, or your loved ones, are pretty newly diagnosed, maybe even just a few months out. I hope you're lucky enough to be dealing with something slow-growing enough that you'll be able to not obsess. It took me a while, but I got there. And now I'm coming up very quickly on the  7th anniversary of my own diagnosis. And I feel OK about it.
 
 I wish that same small sense of peace and patience for all of you.


Tuesday, January 6, 2015

Mocetinostat for Follicular Lymphoma

A new phase 2 clinical trial is just starting at Sloan Kettering in New York, investigating the effectiveness of Mocetinostat in patients with DLBCL and, more importantly for us, Follicular Lymphoma.

Mocetinostat is a benzamide histone deacetylase inhibitor. That's probably going to require a little explanation.

If you've been following developments in cancer treatments, the  you know more and more of them are "inhibitors." That is, instead of trying to kill off the cancer cells the way traditional chemotherapy does, inhibitors try to stop (or inhibit) the processes that cancer cells need to live.

For Mocetinostat, that means inhibiting the process that involves the benzamide histone deacetylase. Histones are proteins that help cells structure DNA, so when the cell tries to copy itself, the new copy will be like the old cell. When the histone is messed with (which is what Mocetinostat does), the cancer cell can't make a copy of itself.

It's a little more complicated than that, but you get the basics.

Now, what makes this Mocetinostat trial special is that it relies on genetic profiling, something that has been promised for a while. In other words, we are at a point where we can examine each individual patient's genetics. We know that not all Follicular Lymphomas are the same -- even though they look the same under a microscope, if we look closer we can see that not everyone's FL was caused in the same way. If we can figure out which gene mess-ups caused each patient's cancer, and we can target those mess-ups, then we have a better chance at successfully treating each patient.

And that's just what's happening with this trial. Researchers know that Mocetinostat works best on patients that have mess-ups on two particular genes, known as CREBBP and EP300. These mess-ups happen to be common to DLBCL and Follicular Lymphoma. So patients in the trial first had a genetic profile done to make sure they had those two particular genes affected, and thus have a better chance of the treatment working.

A total of 54 patients will be enrolled. Half of them will be Follicular Lymphoma patients.

This strikes me as pretty typical of what we can expect in the future -- treatments that not only target particular pathways, but that target particular patients. That's the kind of "personalized medicine" that we've been hearing about for a few years now.