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.

Saturday, July 16, 2016

Rituxan Maintenance (It's Back)

Follicular Lymphoma, as most of us know, is a cancer with few answers. There are lots of questions (like the basic, "Which treatment is the best one?"), but 12 oncologists will give you 13 different answers. (I stole that line from Dr. C, the lymphoma specialist I saw years ago.)

Rituxan Maintenance is one of these FL-related issues with more questions than answers. There are a bunch of studies that have been done since I have started paying attention to these things, and they seem to go back and forth -- one will have evidence that RM is a good thing, and then another will say it's more bad than good. And still another will say is does some good, but it isn't necessary.

So it's hard to know what to make of Rituxan Maintenance. (And if you need a reminder of what it is and how it works -- and more detail on the controversies of whether it's worth doing -- here's Lymphomation's take.)

The most recent addition to the long conversation about Rituxan Maintenance comes from the journal Cancer, in an article called "Randomized phase 3 study in low-grade lymphoma comparing maintenance anti-CD20 antibody with observation after induction therapy: A trial of the ECOG-ACRIN Cancer Research Group (E1496)."

The study is a follow-up on a trial from the ECOG-ACRIN research group, which actually began the trial long ago (the fact that patients in the trial were given CVP chemotherapy is kind of a clue for me that this trial started long ago). Their initial finding was that Rituxan Maintenance increased Progression-Free Survival -- the time it takes from treatment until the disease comes back again. So patients who had RM went longer before another treatment than patients who just had the chemo and then observed.

For this study, several years later, they wanted to see if that benefit held up, and if any other benefits (like increased Overall Survival) came through.

So after receiving CVP chemo, 158 patients were given RM (Rituxan once a week for 6 months), and 153 were just observed. After a median of 11.5 years, they found that the Progression-Free Survival benenfit remained: RM patients went almost 5 years before needing treatment, while patients without went 1.3 years (that's a median time for both).

However, there was no difference in Overall Survival between the two groups. So Maintenance might give you a few years before you need another treatment, but you will live the same amount of time whether you get RM or not. This is pretty much in line with other Rituxan Maintenance studies, which find some benefit, but not an OS benefit -- at least not one that's great enough to say Maintenance is a good idea for everyone.

I like their conclusion, that RM "should be considered optional" for patients with indolent lymphoma.  There is some benefit, obviously, and someone who wants to hold of on another treatment within a couple of years might consider it.

As I have said before, studies about Rituxan Maintenance don't really give us answers. It seems like, if we wait a year or so, some other study is going to tell us something that might say the opposite of this.

I'll be very interested when, in a few years, we have enough of an understanding of Follicular Lymphoma biomarkers that we can look at a genetic sample and say with a little more likelihood that some patients will benefit from maintenance and some won't get much out of it.

I'm confident that we'll get to that point sometime soon. Until then? "Optional."

(At least until the next study that tells us that we should all do it.........)

Monday, July 11, 2016

We are Changed by Cancer and Time

Last night, I watched the movie Rent. I hadn't seen it in a long time, and my musical theater-loving kids wanted to watch it.

Rent the movie is based on Rent the stage musical. It holds a place in my heart because my wife and I saw the stage musical about 10 days after I was diagnosed with cancer. I had bought her tickets for Christmas, and I remember we had thought about not going, but we decided the distraction would be good for both of us.

It's actually a really great show, but I had a hard time with it back then. If you aren't familiar with it, it's about a year in the life of a group of friends in 1989/1990 in New York. It's based on Pucchini's opera La Boheme. For the most part, the characters are artists of some type, trying to stay true to themselves while also dealing with relationships that are complicated by the AIDS crisis that was close to its peak at that time. It was a ground-breaking musical with lots of great songs.

But when my wife and I saw the show back then, just after I was diagnosed, the thing that struck me most was how how messed up the characters' priorities were. This is what I wrote in the blog way back then (January 28, 2008, if you want to look it up):

I think, though, that if I had seen it when it first came out, I would have been at an age to appreciate it more. The bohemian, anti-establishment message was a little lost on me. I found myself thinking, "You're cold because your landlord padlocked your building because you haven't paid your rent in a year, and now you're squatting in your old apartment? I have a good idea -- get a job."

I wasn't in a good place then.

But what struck me last night, watching the movie version 8 1/2 years later, is how much I had missed. Stuff I couldn't really have seen, not that soon into my dealing with cancer.

What really struck me last night, almost immediately, wasn't that they were a bunch of kids who didn't want to get jobs. What struck me was how much they relied on each other.

There are a few scenes in the movie involving an AIDS support group (four of the eight main characters have AIDS or are HIV positive). I could never have known, 10 days into my own diagnosis, how much a support group means to someone who is hanging on to hope so desperately. I was still numb when I saw the stage show. Desperation was still a few days away.

It's amazing to think about how much I missed that desperation. AIDS isn't cancer, and I can't say I know how someone with AIDS feels, and my own cancer isn't the death sentence that AIDS was in 1989. But it felt like it at times, early on. In one of the support group scenes, the members stand in a circle and sing about their fears:

Will I lose my dignity
Will someone care
Will I wake tomorrow
From this nightmare?

It's a heartbreaking scene. They know they are helpless in stopping their disease from getting worse. And even worse, it's a slow decline that they have probably seen in their friends.

If I had seen this show a month later, I think I would have focused on the fear, more than anything. I don't think it would have been that specific a fear, about dying with dignity. But I do remember feeling that there was nothing I could do to stop it from coming. I remember thinking, early on, how messed up it was that I pretty much knew how I was going to die. I wouldn't even have the luxury of being surprised.

But I didn't focus on that. I focused on how small some of the characters' problems were -- paying rent while staying true to themselves.

And it all made me think about how much has changed since I was diagnosed.

That reaction really sums things up for my early life as a cancer patient. I was the impatient patient. Maybe because watching and waiting requires so much energy to NOT think about cancer, I was impatient in everything else in life. I'm generally a laid back person, but back then, I just couldn't stand the idea of people wasting time on things that didn't matter. Work was hell sometimes, because I work in a field where we have to spend a lot of time talking about things in a very small detailed way. And some things really do require that kind of detail. But somethings don't. And I would lose my mind sitting in meetings when I could have been doing other things.

I remember, in the months after I was diagnosed, getting pulled over by a police officer for talking on my cell phone while driving, which is illegal in my state. But I WASN'T on my phone. I think I was just leaning on my hand, waiting for the light to change, and from behind, it looked like I was holding a phone to my ear. And I argued with the police officer, which was justified, but very unlike me. As I said, I'm usually very laid back, and respectful of authority. But that post-diagnosis impatience was in full swing, and I wasn't tolerating anyone who wasted my time.

And over time, that changed. I'm back to being patient and laid back, at least most of the time.

So when I watched Rent last night, it wasn't impatience that came out. It was mercy.

That's the word that came to me. Mercy.

I think much less about myself and the way I want the world to be for me. I think I'm more likely now to see others' suffering and want to help. Or at least to identify with it and feel bad.

Cancer changes us. Probably in lots of ways, over time. I think that's especially important for those of us who have more time to live with it than we might have thought at first.

I don't want the message here to be that cancer makes us better people. I'm not sure it does, and I don't think it should. I'm not someone who sees cancer as a gift. And I'm not someone who thinks we need to be positive all the damn time. Cancer didn't make me a better person, at least at first. It made impatient and selfish -- someone who sees people dying on stage and wishes they'd stop whining and get jobs. Cancer made me a jerk.

But things change over time. And if I got anything out of Rent this time around, it was that, even as people carry their own burdens, sometimes they are able to see the pain in others, and do something to make the world (or just their small piece of it) a better place.

I like that message a whole lot more.

Tuesday, July 5, 2016

Understanding Transformed FL

Two articles from The Journal of Clinical Oncology on Transformation in Follicular Lymphoma. The first, "Risk Factors and Outcomes for Patients With Follicular Lymphoma Who Had Histologic Transformation After Response to First-Line Immunochemotherapy in the PRIMA Trial,"describes the results from a large study of FL patients. The second, "Will a Better Understanding of the Problem With Transformed Follicular Lymphoma Lead to Better Outcomes?" is a commentary on the first article. They both have some interesting things to tell us.

The research article is the latest in a bunch of studies that are trying to understand Transformation a little bit better. There's still a whole lot we don't know about transformation, even basic stuff like why it happens. We know what happens, but we don't know enough about why it happens to be able to predict it. It's always kind of sad surprise when it happens. And a study seems to suggest something about Transformation, but then other studies contradict it, or can't confirm it strongly. It's frustrating, and partly why Transformation is such a scary thing.

The research article looked at over 1000 FL patients over 6 years. A few things that struck me as important:

They identified certain things as risk factors for Transformation. I'll say it again -- these are RISK FACTORS, not guarantees that Transformation is going to take place: altered performance status (I assume they mean a change in your ability to care for yourself, which is what "performace status" usually means), high LDH (Lactate Dehydrogenase, common in FL blood tests, it measues cell damage) “B” symptoms, a grade of 3a, and a high FLIPI score.

Again, those are RISK FACTORS -- it means you have to be a little more careful in keeping an eye out for symptoms. Patients with risk factors aren't guaranteed to transform, and patients without risk factors can also transform.

Like I said it's unpredictable, and that's what makes it scary.

The research article also suggests that an Autologous Stem Cell Transplant might be a good idea for transformed patients, and that a biopsy should be taken when the FL comes back after the first treatment, to be sure it hasn't transformed. (There are some other results, too -- worth looking at the link.)

The second article, the one that comments on the research article, is also interesting, but also a little frustrating in some of the things it says.

The article looks at the research article above, plus three other articles about Transformation, all published in the last 3 years. The author says that these four articles together tell us a lot about what we know about Transformation, and it's a lot that we didn't know before.

For example, in addition to confirming the risk factors from the research article above (high LDH, grade 3, and a high FLIPI), the studies also seem to agree on a transformation rate of 2% over the 10 years after diagnosis, or a 20% change of transforming (a lot lower than some estimates I have seen, though a little higher than others).

But the article also makes it clear that the four studies are hard to compare to one another, since they all look at slightly different groups of patients, and look for slightly different things. So while there are some common risk factors, I'm still a little hesitant to use stronger language than "risk factors." I think we're all on the look out for transformation (it is, as the article says, "the greatest fear of patients and their medical teams.") Interesting that they say it's a fear for the medical team, too -- I think that reflects the kind of frustration that our oncologists have in trying to predict where our disease will go, and then what they should do to treat it.

The article ends with a wish that we will someday soon have a better way to predict Transformation. It cites a few articles that have done some early identification of possible markers for Transformation, including IRF-4 (a gene that codes proteins), miR-31 (which helps suppress tumors, so having less of it is a bad thing), bcl-2 (which helps control cell death), pleuripotency (which describes cells that can develop into any cell in the body), and nuclear factor kappa B pathway genes (which helps cells divide normally). There is no strong proof that any of these things are responsible for Transformation, but there is some suggestion that they might play a part.

Maybe we'll find that there is a combination of these factors that work together to make Transformation happen? And then we'll be able to target those things with new treatments?

It would just be nice to know something, wouldn't it?

In the meantime, we seem to know a little bit more with every new study -- even if what we know is that we don't know as much as we wish we knew. The best thing we can do as patients is, I think, stay alert to changes in our selves, and try not to panic.

You know, the stuff we're used to doing anyway.

Wednesday, June 29, 2016

Watching and waiting?

I'm behind on this, like I'm behind on everything these days: Nice article from the June 9 issue of Blood, called "Is watch and wait still acceptable for patients with low-grade follicular lymphoma?"

I haven't written about watching and waiting for a while, because I was tired of reading articles that said they had the answer about whether or not it was still a good strategy, and then it turned out that they really didn't have the answer. Obviously, I have my thoughts on watching and waiting -- I think it's an acceptable thing, and I did it for two years, and I would make that same choice today.

I'm not sure there really is a definitive answer here, either, but I'm not sure that they are trying to give us one. It's more a review article, looking at what we know about Follicular Lymphoma and whether or not that can tell us anything about watching and waiting.

And there's lots that we know.

We know that median survival for FL has gone up over the years, and that Rituxan probably has something to do with that. There are some experts who say that we shouldn't bother with watching and waiting because one of the reasons for it was because it let us hold off doing any kind of treatment. When there are limited treatments, and they have nasty side effects, it's better to hold off on treatment for as long as possible. But now that we have Rituxan, plus more good treatments on the way, may be we don't need watch and wait anymore?

We also know from several studies that patients who do watch and wait have no real difference in Overall Survival. Some studies show small differences in things like time to progression -- how soon a patient's disease will grow to the point where treatment is needed. But no survival difference. And if that's the case, maybe watching and waiting is OK to do? As my dear Dr. R told me, it's better to do no harm, and as nothing was changing, observation was a fine strategy.

We also know that major cancer organizations' guidelines call say that watching and waiting is acceptable for certain FL patients -- basically those who don't have symptoms, and have a slow-growing form of FL. You'll find that advice in guidelines for groups from the U.S., the U.K., Canada, Italy, and Europe at large.

What would be great, say the authors, is if we had a biomarker that told us that watching and waiting was the best choice -- some kind of gene or protein or enzyme that let us know that the patient would not progress quickly. Amen to that. It would be wonderful to know how this messed up disease is going to behave in the future. But so far, we aren't there.

I'm pleased that the authors at least nod toward the emotional aspects of watching and waiting, giving it one sentence: "A physician’s enthusiasm for watch and wait in this setting should not override the patient’s preference for therapy based on anxiety about not treating a known cancer."

But I'd sure like to see more than one sentence.

I've said before that Follicular Lymphoma is as much an emotional disease as a physical one. It has to be -- as patients, we have more time to think, and for most of us, at least at some point, those thoughts are going to be negative. Especially at the time we need to make that decision -- soon after we get the news that we have cancer. You can show us all kinds of charts and statistics about Overall Survival rates. But our thinking brains aren't working at that point. It's our feeling brains that are making the decisions for us. We need someone who knows how to talk to us at that point.

I'd like to see an article aimed at oncologists that talks about how to consider a patient's emotional state when describing watching and waiting as a treatment option. More than a sentence -- I want a whole article.

So, yeah, in the end, this review article does a nice job of laying out what we know about FL and watching and waiting. But it still isn't giving me any answers. We need to write about watching and waiting in a new way. Someone needs to write that article.

(Maybe it will be me......)

Wednesday, June 22, 2016

Long Live Zevalin

I'm not getting through the ASCO posts as quickly as I have wanted to. There's some interesting stuff, but nothing that has really blown anyone away -- at least not anything dealing with Follicular Lymphoma.

But here's another good one: "Single center experience of 90Y-Ibritumomab tiuxetan in the older population with non-hodgkin lymphoma."

90Y-Ibritumomab tiuxetan is better known as Zevalin, the RadioImmunoTherapy treatment that has never gotten the love from the oncology community that it has deserved. This study looked at patients from one treatment center who were given Zevalin as a consolidation treatment (a treatment given soon after an initial treatment as a way of trying to clean up more of the cancer) or a salvage treatment (a follow-up treatment after one that didn't work). The patients were older, and the results were very good: an 89% Overall Response Rate, with 36% of patients in the consoloidation group going from a Partial Response in their first treatment to a Complete Response with the Zevalin; and 55% of patients responding in the salvage group.

Great numbers, right?

It's one more study in a long line of studies that show how effective Zevalin can be for NHL, and FL in particular.

So why is there no love for Zevalin?

Lots of reasons, but one of the biggest is that it's tough to find someone who can or will administer Zevalin. That's been the case from the beginning, for reasons that have nothing to do with its effectiveness as a treatment.

And now, Zevalin might be gone for good.

Here is a link for an excellent article from Jamie Reno, a great writer and Lymphoma Rock Star in his own right. He's a Follicular Lymphoma survivor himself -- someone who benefit from Zevalin. He describes the problems that Zevalin is facing, and why it might be going away (again, it has nothing to do with its effectiveness).

The article quotes Betsy De Parry, another author and FL survivor, thanks to Zevalin, and Karl Schwartz, President of Patients Against Lymphoma/Lymphomation -- all the Lymphoma Rock Star advocates are getting in on this one!

And we need them to. We all need to get in on this one. I always use the phrase "another arrow in the quiver," which is the phrase that Dr. C used -- the lymphoma specialist I saw a few days after I was diagnosed. It means another weapon that we have in reserve. For FL patients, we have a lot of weapons, and better ones on the way.

But it still hurts to think that a really good arrow might be taken away for good. Let's hope that doesn't happen, and let's thank the folks who are trying to make sure that it doesn't.

Wednesday, June 15, 2016

ASCO: Marriage and Blood Cancers

Another review from the ASCO conference. I found this fascinating.

Apparently, research has shown that cancer patients with solid tumors have a higher Overall Survival when they are married, compared to unmarried patients. So researchers asked, is the same thing true for patients with blood cancers?

The answer was presented in "Impact of marital status on the survival of patients with hematologic malignancies reported to the California Cancer Registry." Researchers looked at records of over 58,000 patients in California with blood cancer, diagnosed between 2000 and 2009. Of course, Follicular Lymphoma patients were included.

The researchers did some statistical analysis on all those records, and determined how marriage status affected Overall Survival, adjusted for age, sex, race/ethnicity, treatment, insurance status, and neighborhood socioeconomic status.

In almost every category, married blood cancer patients had a higher OS than unmarried patients. The highest OS was among married patients with higher socioeconomic status, for certain blood cancers, including Follicular Lymphoma.

So what it is about being married that potentially leads to higher OS rates? (And it's worth remembering that all of this involves statistical analysis, and marital status is no guarantee of anything for any individual patients)

I guess the answer that makes the most sense is that being married means you most likely have easy access to a support system -- emotional support, physical support, spiritual support. I know from my own experience that dealing with my diagnosis, my watching and waiting, and my treatment were all a heck of a lot easier because of my wife. In fact (I've told this story a lot) my first few weeks after diagnosis were hell because I refused to rely on my wife. It was only after I used that support that things got easier for me emotionally.

Now that certainly doesn't mean that unmarried patients won't do well. But it does seem to confirm that people with a support system have an easier time. The researchers suggest there should be more research done in this area, looking at some other factors affect unmarried patients -- things like social support, sticking with a treatment, and healthy lifestyles (all things that are probably helped by having a spouse who reminds you to take your medicine and eat your vegetables, and gives you a hug every now and then).

I think the big lesson here is that our lives are made easier with some kind of support, whether it's from a spouse, a family member, or a good friend. Cancer is way too hard to handle by yourself.