Tuesday, December 31, 2013

Follicular Lymphoma: The Best of 2013

For the last 3 weeks or so, I've been seeing lots of end-of-the year lists, proclaiming the best of, or the worst of, or the top whatever: Sports Illustrated's top sports moments of the year, for example (one too many sad Boston sports moments in there), or Ralfy's Single Malt Scotch of the Year for 2013 (an excellent choice).

I thought it might be fun to put together my own "Top 10" list for Follicular Lymphoma. Despite what the blog post title says, this isn't necessarily the ten "best"; it's not even the ten most significant. More like the ten that struck me most.

I know some of these end-of-year lists are designed specifically to get people discussing, and this one is probably no different. So feel free to argue for a different order, or to leave some things out altogether and suggest new ones.

Here they are, in descending order:

10) Approval Sought for Idelalisib/CAL 101 for Indolent Lymphoma. This could potentially be higher that #10, but I'll let you fight that out. Gilead, manufacturer or Idelalisib, submitted an early application to the FDA, based on phase 2 clinical trial data. Significant for a couple of reasons: it's the first kinase inhibitor to go through the process, and an approval could bolster other phase 2 data-based applications (and maybe speed things up for other treatments). I've been following this for a little while, because some support group folks were in the trial, and were having some great success.

9) Ibrutinib Makes Everyone Lose Their Minds with Excitement. The FDA approved Ibrutinib for Mantle Cell Lymphoma patients in November, giving it "Breakthrough Status" and approving it early. It also achieved a 100% response rate in 15 patients (10 complete, 5 partial) when combined with CHOP in DLBCL patients in August. It's currently in a phase 2 trial for Follicular Lymphoma, and its mind-loss-causing abilities seem like they might be justified.

8) GA101 plus CHOP Kicks Butt. Results of a phase 2 trial of Follicular Lymphoma patients showed that G-CHOP achieved a 93% response rate. GA101, also known as Obinutuzumab, seeks to be an improvement on Rituxan; it is humanized (no mouse parts) and glyco-engineered (designed to latch on better). A phase 3 trial seems to be justified.

7) Some Guy Stays Alive for 5 years and Thinks He's Special. I wanted to include someone telling his or her story of being a Follicular Lymphoma patient, and I thought, "Why not me?" So here's my Lympho Bob entry from last January 15, when I celebrated my 5 year Diagnosiversary. It might seem a little pompous, but it's really quite the opposite -- take it as an example of my humility and self-control that I didn't put myself higher. (And yes, I beat out the other three, because none of them are FDA-approved for FL yet. At least I did something...)

6) Learning from Cancer. OK, so my own story isn't the only one to make the list. I have to include something from Michael Buller's Thinking Out Loud blog. My all-time favorite post of his is his Top 10 Perks of Being Treated for Follicular Lymphoma -- funny, insightful, very positive and hopeful -- but written in 2012. My favorite from this year is 10 Things I've Learned from Cancer -- equally insightful and inspiring truths -- lessons that I hope any newbies learn along the way. (Bonus: there's a part 2.)

5) Transformation no so common? This one is exciting and hopeful, but worth being cautious about. Researchers found that the overall transformation rate for 600+ Follicular Lymphoma patients was under 11%, far less than the 30% that seems to be the consensus. Excellent news, but I've seen the figure anywhere from 15% to 50% of FL patients will transform. This gets #5 based on the hope it inspires, but I'm still not sure we're suddenly that low.

4) Bye Bye Bexxar. This is why it isn't really a "best of" list -- Bexxar, one of our RIT options, is not going to be made anymore. Nothing worse than our quiver being an arrow short. Jamie Reno (speaking of "best of") wrote about his own experience with Bexxar, and his disappointment, in reporting on the decision. Plus, Jamie's just worth reading. You won't find too many better writers on cancer.

3) Bendamustine Kicks Butt Even Better than CHOP.  A researcher team has been pitting  Bendamustine against R-CHOP for several years: head to head, mano a mano, B cell to B cell. After giving updates at conferences, they finally subjected their results to peer review. Bendamustine won big -- better results with fewer side effects. Probably cemented Bendamustine + Rituxan as the preferred first treatment for Follicular Lymphoma (along with Watching and Waiting, straight Rituxan, and a bunch of other things). Worthy of the bronze medal.

2) Survival Stats. When I was first diagnosed, someone wrote to me to tell me how worried he was that Wikipedia said that the Median Overall Survival rate for FL was 8 to 10 years. Those are complicated numbers to calculate and to explain, but they were fairly accurate -- for 1997. There is some suggestion that our current median Overall Survival is at least 18 years, and likely higher. Lots of reasons that number is also complicated (starting with the ways "median" and "overall survival" are defined), but the number makes my heart skip a beat in a good enough way that it's staying at #2.

1) Rituxan + Pidilizumab for Follicular Lymphoma. I'll admit to a bit of "recency bias" -- the stuff we have experienced most recently is the stuff we tend to believe the most. And since this bit of news came less than a month ago at the ASH conference, I might be giving it too high a ranking just because it's fresh in my mind. But given how excited people are about T-cells and Immunotherapy, I think this one holds the most reason to be excited. Rituxan gets a new best pal in Pidilizumab, which tells T cells to get off the couch and do their job. Extra points for being part of a larger trend, but ultimately the one on the list that gets me most excited.


So while there might be some argument about the list, there's no argument that this was a damn good year for Follicular Lymphoma. We have some pretty special stuff in the pipeline, and even if only a small percentage lives up to its promise, we're in for a bright near future.

Thanks for a great year, everyone. I hope next year is good to you all.

Sunday, December 29, 2013

Follicular Lymphoma and Genetic Profiling

Interesting and encouraging news from the journal Nature Genetics:  new research from Britain gives an even more complete picture of the genetic mutations involved in Follicular Lymphoma, including transformation.

I'll be honest -- I haven't read the full article. I don't get free access for a few months, and they want $32 for a copy of the article. I can't afford it at this time of year. Spent my last $10 on a handmade nose warmer for my wife. (Not really, but her sister did buy her one, and she loves it.)

So I'm getting my information from a report from MedicalXpress and from the abstract for the original article. But even those less-than-ideal sources show that there seems to be some really good stuff from this research.

The researchers did a series of genetic analyses of the DNA of a single patient as his or her disease progressed over time. By doing this, they were able to map out the initial genetic mutations, but also see if any new ones popped up when this patient transformed from indolent Follicular Lymphoma to a more aggressive form.

What the researchers hope is that they have found a number of mutations that can help them target FL at a number of stages: at the initial onset of the disease; when it begins to resist treatment (which happens for most patients, which is why we need to switch to different treatments along the way); and at transformation. Much of the newer research is very targeted to genetic mutations, so it's possible that different treatments could be created to deal with Follicular Lymphoma at these different stages.

In case you're wondering, the specific mutations were identified include those in linker histones (histones are the proteins that the DNA winds itself around to form a spiral shape; linker histones kind of seal of the ends of the spiral); JAK-STAT signaling pathways (this is one of those Kinase things that are, in general, an important part of FL research these days); and NF-κB signaling (a bunch of proteins that are involved with transcribing DNA, making sure it gets copied correctly when a cell divides). Plus some others. You know, just in case you were wondering. (I love you little cancer nerds who bothered to read to the end of the paragraph.)

Very important early research, but with the usual cold water:
First, it is indeed early research. They've identified the mutations. It will likely take years to find treatments that will target these mutations, and then more years to test them in trials and get them approved.
Second, this is the DNA of a single patient. We know how complex cancer is, and it is probable that these are not the only mutations that lead to Follicular Lymphoma, or resistance to treatment, or transformation. But it's a good model to follow on other patients to get a bigger picture.

So, as always, we shake off the cold water and towel ourselves off with a little more hope for the future.

Good stuff.

Friday, December 27, 2013

Immunotherapy is #1!

The well-respected journal Science named cancer immunotherapy its breakthrough of the year for all of science (beating out significant research on human cloning, among other breakthroughs). It's a nice stamp of approval for something that might be able to affect all of us in the near future.

Immunotherapy is, of course, the general name for the processes that try to get the body's immune system to fight cancer on its own. The article cites some amazing results on stage 4 melanoma patients, and perhaps more relevant for us, on acute lymphocytic leukemia (which I wrote about recently) with T-cell therapy, where the patient's T-cells (which normally attack invaders) are removed and re-engineered to recognize cancer cells, and then put back in.

The big reason, it seems, for giving the breakthrough award to immunotherapy is that it has changed the way researchers look at cancer. The focus isn't on the tumor or the cancer cells, but on the immune system. Instead of changing the cells (say, with chemotherapy), it's about changing the attack system. It's like building a team around pitching and defense rather than big bats.

Of course, immunotherapy has been in around for a while. Antobodies like Rituxan are technically a type of immunotherapy, though it works in a different way than the re-engineered T-cells. But it's the same general principal -- use what we know about the body's defenses to help the body defend itself.

As the article notes, we're still pretty early in the research here, especially with T-cells. It works amazingly well for some patients, but not all. And as for Follicular Lymphoma, we're even earlier in the research than for melanoma or ALL. And I'm still personally still impressed with cancer's ability to find ways around our attempts to fool it. So we're still a way off with all of this.

But, as I said, it's quite a stamp of approval from Science, and certainly reason for hope in the (perhaps near?) future.

Tuesday, December 24, 2013

Merry Christmas

A couple of weeks ago, some students from Berklee College of Music did a "pop up performance" at the Museum of Fine Arts in Boston, singing "O Hold Night" in the cafeteria.

It kind of has it all for me. For one thing, I love a flash mob -- people showing up unannounced and bringing some unexpected joy to others, just for a few minutes.

Plus, "O Holy Night" is one of my favorite Christmas songs. And the young man who sings lead, Mark Joseph, just nails it.

Plus, it's at the Museum of Fine Arts, which brings back some nice memories of living in Boston. On one side of the MFA is Northeastern University, where I met my wife. On the other is the Fens, and behind that, the neighborhood where my wife (then my girlfriend) lived. I spent lots of time walking behind the MFA with Isabel on the way to class.

And finally, there's Berklee, where my son spent a few days last summer at a jazz saxophone workshop. I don't post braggy videos of my kids much any more, but they still bring me just as much joy, particularly with their music.

Quite the formula for happiness.

I want to wish a Merry Christmas to all of you who celebrate it. And for those of you who don't, I wish you a day full of peace.

Sunday, December 22, 2013

Sloan-Kettering on Lymphoma

Sloan-Kettering has a series of videos, posted a few days ago, that come from an early October forum called Lymphoma: The Latest in Diagnosis and Treatment.  It's a series of 5 videos, lasting about an hour in total. I'm going to post the first one here, called "Understanding Lymphoma."

The panel consists of three of the big names at Sloan in blood cancers.

It's an interesting series, though I would caution against paying too close attention to it. It's about lymphoma -- all 75 types of lymphoma -- Hodgkin's and Non-hodgkin's, B cell and T cell, indolent and aggressive -- break it down any way you like. So if you're feeling particularly cancer-nerdy, it's a nice, but very incomplete overview of lymphomas.

Just pay real close attention, and make sure that whatever they are talking about is really relevant to your situation, and not someone else's.

If you want to focus on one segment in particular, go with "Advances in Treatment Options for Lymphoma." Even if, say, radiation isn't likely to be in your future, it's always fun to watch cancer experts get excited about future treatments.

(I know this is a short one; expect the next few posts to be short. Lots to do as the holidays speed up toward us. They'll get longer soon.)

Wednesday, December 18, 2013

ASH: Patient Power

As I predicted a couple of days ago, the website Patient Power has posted its quick summary of the ASH conference. "more excitement among blood cancer specialists than ever before."

I think the big winner at ASH was CLL -- Chronic Lymphocytic Leukemia. CLL isn't my area, so I don't follow it very closely. But it's pretty clear that the major stuff that came out of ASH was related to CLL. I'm happy for them.

But I think Follicular Lymphoma did pretty darn well, too. Andrew Schorr, founder of Patient Power, mentions Follicular Lymphoma briefly, pointing out that there are some new combinations, and more treatments that will let people live with FL for a long time as a chronic condition. He promises more videos on some of the specifics soon. In the past, that means interviews with Lymphoma Rock Star-level experts about the things that they were excited about in their fields.

Schorr's video segment is called "Optimism and Changes Ahead for Blood Cancer Patients," and while it is short on details (for now), it certainly does convey that optimism. He finishes up with this: "The word here is excitement -- probably more excitement among blood cancer specialists than ever before."

Sounds great to me.

Monday, December 16, 2013

ASH: Blood Cancer Blood Test

This is about a week old now, but it's worth taking a look at: a post-ASH press release from Sloan-Kettering touting its new blood test, to be used as a diagnostic tool for blood cancers.

The blood test will look for 400 variations in genes that signal a blood cancer. It could, for example, show that chromosomes 14 and 18 have switched places, which would indicate that the patient has Follicular Lymphoma. Those 400 different variations can detect a variety of lymphomas, leukemias, and myelomas.

Here's why it's important: because it will be used as a tool not only for diagnosis, but for treatment decisions as well. As genetic research gets more and more sophisticated, we are finding that cancers that seem the same under a microscope might actually be different if viewed on a genetic level (that is, much more closely than we can see with a simple microscope).

To give you a Follicular Lymphoma example, a key sign of FL is the 14;18 translocation, with those two chromosomes switching places and causing all kinds of problems -- it basically shuts of the bcl2 protein that tells the cells to die. However, Follicular Lymphoma also sometimes shows another switching involving the protein BCL6. Now, a standard look through a microscope will show that the cells from a biopsy look the same -- like Follicular Lymphoma cells. But only a genetic analysis will show that there is either one or two of those chromosome switches taking place.

Now imagine that we have a patient diagnosed with Follicular Lymphoma who had the new Sloan-Kettering blood test. Her doctor knows that the 14;18 chromosome is often dealt with successfully with something like Bendamustine. But imagine that this doctor also knows that early results from a clinical trial for a new treatment (let's call it Bobimab) has shown remarkable results if the patient has BOTH translocations. The doctor knows that this patient would be an excellent candidate for that trial because the test shows both translocations.

Much less guessing. Much more targeted treatments. This is what personalized medicine is supposed to be all about.

(And if anyone from a pharma company or a university lab is reading, please feel free to name your next Monoclonal Antibody after me. Bobimab is much less intimidating than what you usually name things, with all of those Vs and Xs and Zs.)

For now, the test will take 3-4 weeks to get results back. For someone with Follicular Lymphoma, that's not a big deal. For someone with a more aggressive blood cancer, treatment will have to start right away, so maybe it would be more useful for a second round of treatment. I can also see the test getting easier over time, with results coming back faster (though that isn't something that Sloan-Kettering is promising).

All in all, I think this should be bigger news than it is. All or most of this information is already available, but I think this is the first test that can detect so many variations at once. And I'm guessing the test is scalable: as more genetic information is discovered, it can be added to the test.

Very cool stuff.

Friday, December 13, 2013

Rituxan + Pidilizumab for Follicular Lymphoma

I think most of the main ASH announcements are over now. We'll have to wait for the post-ASH commentary that will likely come over the next few weeks. (I imagine Patient Power, for example, will have a wrap-up video sometime soon.)

But does that mean the Follicular Lymphoma news is over for now? Absolutely not. In the latest issue of The Lancet Oncology is a report on a phase 2 study of Rituxan and Pidilizumab that shows some promise -- good activity against Follicular Lymphoma cells, with side effects that aren't too horrific.

I'll be honest -- I don't know a whole lot about Pidilizumab. From what I can tell, Pidilizumab has been studied as a treatment for solid tumors as well as lymphomas. A phase 2 study of DLBCL patients after auto stem cell transplant was pretty successful. I believe that this is the first phase 2 on Follicular Lymphoma patients.

Pidilizumab seems pretty cool. It is, like Rituxan, a Monoclonal Antibody (which is why it has that -mab ending on the name). Just as Rituxan targets the protein CD20 on B cells, Pidilizumab targets something called PD-1, which stands for Programmed Cell Death 1. PD-1 does a job we don't want it to do: it blocks T cells from killing off the cell. So when a cell has PD-1 on its surface, it signals to T-cells that it should be left alone.

So guess what kind of cells has PD-1 on it? Yeah. Follicular Lymphoma. Grr. The FL cells have other substances within them that trigger PD-1 to block the T cells.

But Pidilizumab seems to do the job. It targets PD-1 and blocks it, thus allowing T cells to come and do their job. (It "unleashes" the T cells, as the article puts it, which sounds much cooler.)

So how successful is Pidilizumab, when combined with our old pal Rituxan? In this small phase 2 study, 29 Follicular Lymphoma patients were given the -mab combo, and 19 of them (66%) had a response, with 15 of those 19 (a little more than half overall) having a Complete Response. That's pretty good.  Rituxan has about a 40% response rate, with 11% CR. So combining the two increases the effectiveness.

More importantly, it does so with about the same side effects as Rituxan alone.

So Pidilizumab certainly seems like a keeper. Obviously, a phase 3 trial, with more participants, is going to be the next step. There's some suggestion that maybe trying it on its own, in a trial with a direct comparison to Rituxan, might also happen in the future.

Certainly something else to keep an eye on. Maybe another arrow in the quiver.

Wednesday, December 11, 2013

What Does The Spleen Do?

I guess there's an OK chance that you've actually seen this video, since it's had 500,000 views on YouTube in 2 days, but I'm posting here because I thought it was pretty funny.

It's a parody of the very popular video (over 250,000,000 views) "What Does The Fox Say?" which tries to answer, in song, the question of its title. That video/song was created by the Norwegian band Ylvis. Extremely silly, very catchy, and lots of fun.

The video I am embedding below is called "What Does The Spleen Do?" and it was created by a group from the Harvard Medical School. It also attempts to answer the question of its title -- with much less success, but with all the catchiness of the Fox song.

This is, of course, very relevant to Follicular Lymphoma; stage IV lymphomas often have spleen involvement.  Dr. R taps on mine regularly.

For the record, the spleen really is a blood filter (which is why B cells can collect there), and plays some other roles in immunity. But what's more important, after you watch the video, is knowing what it doesn't do.


Sunday, December 8, 2013

ASH: Gene Therapy

The ASH stories keep rolling in.

This one is from Yahoo! News -- a big enough deal to make it to the mainstream press. The piece is called "Gene Therapy Scores Big Wins Against Blood Cancers." The focus is not on Follicular Lymphoma, but it seems important enough, and adaptable enough, to consider it a possibility in our futures.

Gene therapy involves removing T cells and reprogramming them to go after cancer cells. A little reminder about how the body normally works: when an invader (bacteria, or a virus) enters the blood stream, it is attacked by white blood cells. There are several types, including B cells (which go nutty in ways that result in Follicular Lymphoma) and T cells, which attack the invaders in a variety of ways. (Here's a nice video that shows you more detail, if you're interested.) As long as things are working normally, the immune system can identify anything that doesn't belong and take acre of it. 

Of course, cancer is the definition of things not working normally. Cancer cells don't belong, but they are able to mask themselves in ways that make the immune system think that they do belong. And they have the nasty ability to figure out how to get around any attempts to get them to drop that mask. (Cancer cells are stupid smart.) 

Gene therapy messes with cancer cells in cool ways. T cells are removed from the patient's body and then reprogrammed in ways that allow them to get behind the mask, identify cancer cells as invaders, and get rid of them. 

This isn't a single process; there are several presentations, from different teams, targeting different cancers, that fall under the general idea of "gene therapy." It seems like one project that targets leukemia (both acute and chronic) is the longest and most successful. The Yahoo article discusses a couple of others that deal with "lymphoma," but they don't give any indication of what type (Hodgkin's or Non? Aggressive or Indolent? Can't say.) I tried to search the ASH abstracts using just the names of the universities that are mentioned in the article, to see if I could find which sessions discuss gene therapy. I couldn't find them very easily. Oh well. 

I also looked in the "ASH News Daily" newsletter that gets published during the conference, to see if there is anything in there about it. I'll look more later; I got too distracted by the "Hematology Crossword Puzzle" on page A8 of the Saturday edition. (The clue for 16 Across: "Pre-endoscopy rectal cleansing." Five letters. I wish I was kidding...Don't doctors want some vocabulary-based entertainment that gives them a little bit of a break from work, for crying out loud?)

Anyway, the Yahoo article is certainly exciting, and it's one more reason for some hope. I've got a couple more press releases and news stories that I'm looking at, that I hope will be worth sharing over the next couple of days.)

Saturday, December 7, 2013

ASH Day! Zevalin and Follicular Lymphoma

It's opening day of the ASH Conference! Woo hoo! Lots of talk about blood cancers from some stupid smart people!

(I'd normally go all Boston with that and say "wicked smaht," but yesterday I overheard two college students talking about the Honors College at their school, and one of them said, "Yeah, you have to be stupid smart to get in there." I love it. I assume he was using "stupid" as an adverbial intensifier, like "very," or "wicked." I'm going to try to find any excuse to use that phrase all the damn time now.)

Anyway, today is the opening day of the ASH conference, and that means lots of drug companies and universities will be putting out press releases over the next week to tout the results of the research that will be reported at the conference. I saw my first last night, from Spectrum Pharmaceuticals.

I like Spectrum's press release, because it mostly gives information without any spin, which some press releases give. (Of course, there's only so much spin a drug company can give without the FDA getting upset.) But Spectrum provides the session numbers and titles of the presentations that involve their products, and some basic information about the products themselves.

They highlight three treatments that are being discussed at ASH. The first is Folotyn, which is discussed as a treatment for T cell Lymphoma and for Multiple Myeloma. The second is Marqibo, also known as Vincristine Sulfate Liposome, which is already approved for Acute Lymphoblastic Leukemia (ALL), and is here discussed as part of a treatment regiment for DLBCL. I like that one of the presentations is substituting Marqibo for a the NON-Liposomal Vincristine in CHOP, which makes CHOP into CHMP, which is perfrect, because Marqibo sounds like the name of a species of monkey that my son the animal lover would be especially fond of.

Enough monkey jokes: Marqibo is like Oncovin, which is the "O" in CHOP, but it is covered in a fat-like substance that slows down how quickly it is absorbed by the body. The idea is that this may cut down on toxicity, and also allow it to stay in the bloodstream and do its job a little longer. That's what the ASH presentations are getting at.

As you know, I know a little about DLBCL, and much less about T Cell Lymphoma, ALL, and Myeloma, so I won't say anything else about those other Spectrum products. But it's the third one discussed in the press release that is relevant: Zevalin.

Zevalin is a type of RadioImmuno Therapy (RIT) that uses Rituxan, which can find CD20 markers on Follicular Lymphoma cells, to deliver a little shot of radiation directly to the cell. It's a very cool, extremely underused treatment for Follicular Lymphoma, and I'm very happy that it's getting so much play at ASH. The other approved version of RIT, Bexxar, has been effectively discontinued by its manufacturer, so we need some good news about Zevalin to keep the RIT option alive for us. Spectrum highlights seven different presentations at ASH that discuss Zevalin.

Not all of the presentations offer good news for Zevalin, but enough of them do for Spectrum top brag about them. They confirm that Zevalin works well when administered after other treatments when there is miminal remaining disease, extending the effectiveness of the initial treatment; but also that Zevalin works well as an initial treatment in indolent lymphoma, even with bulky disease (larger tumors), which seems to go against some previous studies. However, it seems less effective, and less cost-effective, than Rituxan Maintenance.

ALl of which might explain why there was less spin in the press release: kind of a mixed bag when you look at the overall results.

So I'll provide my own spin (reminding you, of course, that this comes from a Cancer Nerd, and not a medical professional): the less-successful outcomes for Zevalin doe not, and should not, spell disaster for it. If anything, they help us narrow down how and when it can best be used. That's ultimately the point of a trial -- to give us fairly narrow instances for when a treatment is likely to be more successful than another treatment. My hope is that there is enough good news about Zevalin at ASH to keep it out there as an option, maybe even to get people just a little more excited about using it. We already know some circumstances when it is useful, and I think the ASH presentations confirm that. Maybe Spectrum knows that, too, and that's why they bothered putting out a press release in the first place.

I would hate to see Spectrum take the RIT option away completely. That would be stupid stupid.

Thursday, December 5, 2013

ASH: Choosing Wisely

This comes from the American Society of Hematology itself, rather than research presented at their upcoming conference: their list of 5 hematology procedures that should be questioned. I'll say right off that none of them are directly related to Follicular Lymphoma, but it's an important list anyway.

The list was released as part of the Choosing Wisely campaign, sponsored by the ABIM Foundation. The campaign is working with medical organizations like ASH to highlight procedures that are commonly done, but not necessary. The campaign actually has two sets of lists: one for doctors (like the ASH list), and one for patients, with advice on things like when it's necessary to get allergy testing, or have a colonoscopy, or stress tests.

I think the lists are important mainly because they encourage conversation. Often, we have to make decisions as patients when we are not in a state to think rationally. And too often, doctors do things because it's the way they've always been done. The lists encourage us to question ourselves and our doctors, and make sure that whatever decisions we make are the right ones, doing more good than harm.

Now, that said, I think it would be just as dangerous to accept the advice on one of these lists without question as it would to do what a doctor says without questions. And that's the main point here -- ask questions, get information, make good decisions.

As for the ASH list, it offers five "commonly used tests and treatments to question" because they are used improperly. As I said, none deal specifically with Follicular Lymphoma, though one does deal with lymphomas:

"Limit surveillance computed tomography (CT) scans in asymptomatic patients following curative-intent treatment for aggressive lymphoma."

To be clear: these are CT scans after treatment for aggressive lymphomas (say, DLBCL) that have been treated with the intent to cure (with, say, R-CHOP as an initial treatment), when the patient has no other symptoms that would justify a scan. The reasoning behind this suggestion is 1)  there is no evidence that CT scans to look for signs of returning cancer do much to increase Overall Survival, and 2) there is some evidence that all that radiation can cause secondary cancers later on.

So where does this leave me? As an asymptomatic Follicular Lymphoma patient, not much. But what it does do is get me thinking: do I need a scan?

I haven't had one in a long time -- coming up on 4 years in the spring. Do I need one? I don't know. I don't have any symptoms -- and goodness knows I look for them all them time. No bumps that are growing. No weird fevers or chills. My blood work is always good. But part of me really wants to know what's going on inside. Rituxan gave me a Partial Response. Is it any worse? Is there an area growing that I should be keeping an eye on?

I bring this up with Dr. R pretty much every time I see him. And I'll bring it up again. And I'm guessing he'll tell me the same thing he tells me every time: "Yeah, maybe. It's been a while. We'll see how things look at the next appointment and decide if we should do one. It might be time." And then he puts me off again. Which is probably what he should do, given my lack of symptoms.

And that's why I value a list like ASH's: it makes me ask questions and start a conversation with my doctor. Even if it's a question that isn't directly about my cancer, it gets me thinking.

The danger, of course, is that our thoughts sometimes get away from us. I've been doing this long enough to get a post-it and write "ask about CT" and stick on the calendar for January when I have my appointment. Five years ago, reading questions about scans might have had me up at night wondering why I wasn't getting one and what I was missing. I don't miss those days, and I feel for those who are going through them now.

But in the end, asking questions -- and getting answers -- is worth a few hours of sleep. Education is key to survival, physical and emotional.

Monday, December 2, 2013

ASH: Follicular Lymphoma and Lifestyle Factors

OK, I'm going to start this one off with a great big warning about being very careful about what you read. The information in this ASH abstract looks really, really good to me, but we're also talking about a relatively small study (123 patients) that is retrospective (looking back at patients who were treated 30 years ago, in some cases), and it deals with statistical analysis of a group (always something to be wary of when considering the impact on your own life).

The abstract is for a paper called "The Influence Of Lifestyle Factors On Tumor-Related Markers and The Microenvironment In Follicular Lymphoma (FL): Novel Interactions and Collective Impact On Survival," and it looks at the correlation between some specific biomarkers (that is, some proteins on the surface of the Follicular Lymphoma cells) and certain lifestyle factors (specifically, Body Mass Index [BMI], diet, and smoking habits). As I said above, the study looked retrospectively as 123 Follicular Lyimphoma patients, and found some fascinating correlations:

  • Patients with high CD7 biomarker tended to eat lots of fruit, veggies, and starch, especially carotene-rich veggies.
  • Smokers tended to have lower CD7 levels.
  • More fruit was associated with higher CD10 levels.
  • High BMI was associated with higher Overall Survival.
  • High CD7 levels were also associated with higher Overall Survival.
  • High BMI and high CD7 levels combined were associated with even higher OS.
So what might we read from this?

Well, I'm writing this while I take a lunch break, pretty thrilled that my non-smoking, fat-butted/high BMI self is eating a clementine. Hooray for Lympho Bob.

What should we read from this?

Probably not quite as much. I'll say it again -- it's a small retrospective study that found some interesting correlations, but I'm guessing that are plenty of carrot-eaters out there who still struggling with their Follicular Lymphoma. Trends do not add up to individual truths. These trends will need a lot more study before they can really be considered worthwhile, and even then, even with a sampling of 10,000 FL patients, things won't necessarily hold true for individuals.

This is probably a good time to remind everyone of how ASH works, and what it all means. The ASH conference is often the first chance that many researchers get to present the results of their research and get a little feedback. At some point, they will need to subject their results to "peer review" -- having other experts in the field look very carefully at the data and determine if it's all as good as it seems. Presenting at ASH is just the first step. Not all of what we see is going to result in something that shows up at our oncologist's office and treatment room. We have to remember that.

For me, looking at ASH abstracts gives me some hope. It gives me something to look forward to. But there's never any promise of success that goes along with it. If things don't work out, that's OK -- I'm happy to move on to the next thing that might give me some hope.

So the takeaway here probably isn't all that startling. Even if we don't have a definite correlation between specific lifestyle factors and Overall Survival for Follicular Lymphoma, we all know that we shouldn't smoke, we should eat more vegetables and fruits, and we should keep our weight down. That probably helps everyone's OS, not just Follicular Lymphoma patients'.

Still, that whole BMI link to Overall Survival is kind of nice, given how much pie I ate over the last few days....

Thursday, November 28, 2013

Giving Thanks

This past Monday, I had the privilege of reading something I wrote to a small audience. I won 2nd prize in a memoir writing contest -- and a $50 Barnes and Noble gift card to go with it. The memoir had to be 500 words or less, and, long-winded as I can be, I came in a exactly 499 words -- after a whole lot of trimming.

And when I say I read in front of a small audience, I mean just that; I think there were more boxes of free pizza than there were people in attendance. So I ended up with some extra pizza, in addition to that gift card -- plus the applause I got from the audience.

Anyway, every year on Thanksgiving Day, I try to write something about what I'm thankful for. This year, I thought I'd share my 500 word memoir. It's a story I've told before, just not necessarily in this particular form. It is called, appropriately for this day, "The Gift":


"The Gift"

When I first took up running, an experienced friend told me, “Some people who run are running away from something, and some are running toward something.”

When I started running, it was toward something: better health. I wanted to be around for my wife and kids.

Soon, I realized I was running away from something. For a few moments in the mornings, I could block everything out, just listening to music or the rhythm of my breath.

On my 40th birthday, my wife bought me a treadmill. She knew I enjoyed running outside, but she worried about cars not seeing me, or slippery ice, or twisting an ankle far from home. A beautiful treadmill, it sat idle for a month; cool June morning runs were just too tempting.

Then it stayed idle because of a bout of bronchitis. The doctor gave me a prescription, and I asked her when I could run again, and she said, “A couple of weeks.” When I felt better, I finally tried the treadmill. The hiss of the belt and the grinding of the motor and the pounding of my feet were loud, even with my iPod at full volume. I missed the outdoors, and I couldn’t wait to get back to the peace.

The bronchitis never really went away, and I was back at the doctor’s office twice in two months for stronger antibiotics. On the rare days that I could breathe well, my run was on the treadmill. Tree pollen and car exhaust made it too hard to run outside.

Then late in the summer, the bronchitis turned to pneumonia. What should have been peaceful, cool fall morning runs were half run/half walks on the treadmill. To make matters worse, my oldest child, an early riser like me, started to join me in the basement, wanting to talk about the highlights on ESPN, turned up loud, joining the motor and my pounding feet to disturb my peace. Eventually, all that noise got to him, too, and he stopped coming downstairs in the mornings.

The pneumonia cleared, but a follow-up CT scan showed some swollen lymph nodes in my chest. A few months later, more nodes, more tests, and a biopsy that came back fast and grim: Follicular Lymphoma, an incurable blood cancer. Still limping from the biopsy, I asked the doctor when I could run again. “Two weeks,” he said.

Back to the treadmill.

I worried about myself, but I worried more about my wife and kids, and I watched and listened for clues about how they were feeling. One night, my ear to the door to my sons’ room, I heard the older one talking to the younger one. “I’m telling you, he’s OK.”

“How do you know?”

"I heard him running on the treadmill. He’s fine.”

Sometimes when we run, we are running toward something. Sometimes, we’re running away from something.

And sometimes we run because we want to stay, blissfully, even for a little while, right where we are.


I wrote a version of this story about 5 years ago and submitted it to the magazine Runner's World, which often publishes short memoirs about running. They rejected it, of course, which was fine. That version was more focused on running, naturally, and did a lot more explaining about what I considered to be a gift.

When I wrote the piece for the memoir contest, I thought about renaming it "The Treadmill." That would make a lot of sense for a story about having Follicular Lymphoma. It feels like being on a treadmill sometimes, at least for me. Lots of watching and waiting. Rituxan gave me a Partial Response almost four years ago, so there's still come FL cells floating around in there, but not enough, apparently, to need treatment. No scan in more than three years, so I'm not getting better, but I'm not getting worse.

Just walking on a treadmill.

And "the gift" in the title is definitely my birthday treadmill. But that story wasn't just about the treadmill itself; it was about the way I was able to connect to my kids. And that's a gift.

I know lots of people who choose to look at cancer as a gift, at least indirectly -- cancer let them get their priorities in order, pay more attention to their health, or get closer to people they care about. Plenty of others think it's crazy to think of cancer in any way positive.

I guess, if I had to choose one or the other, I'd lean toward cancer not being much of a gift. (Of course, Follicular Lymphoma is the gift that keep son giving -- hah!). I'd never re-gift it, but if I had been given the choice, you can be dang sure I would have politely declined.

Still, on the other hand, I can see where, indirectly, it can result in some good. And if this memoir is as much about my kids as it is about a treadmill, I'd say my cancer has given me some things. I think my kids, now 16, 14, and 12, have become better people because of my cancer. They seem to me to be less fearful. They have seen what it is like to face something difficult and do what is necessary. They certainly aren't fearless, but they are a little less fearful.

And more importantly, they're a little more compassionate. They notice people who need help, and they provide it when they can. Small things, usually, but they can see the big results that can come from small actions. At a time when lots of young people are focusing more on themselves, they are, at least a little bit, looking at others. That makes me very happy.

So, what am I thankful for?

My treadmill. And the relative good health to keep using it. And my wife, for taking care of me.

My kids, who are growing up into fine people.

My extended family, who I wish I had more time to spend with.

And finally, for being able to share whatever gifts I have with all of you. I thank you for the feedback you give me. It means a lot.

Thanks for reading. Enjoy your day.

Tuesday, November 26, 2013

ASH: Dr. Cheson's Preview

Hard to believe it's almost December. All of the signs are out there: 20 degree weather in Connecticut, Salvation Army bell ringers in front of Stop & Shop, and now our first ASH expert preview -- this one from Lymphoma Rock Star Dr. Bruce Cheson of Georgetown University.

Medscape Hematology has a video from Dr. Cheson with some of the things he's excited about at ASH. The video is accompanied by a transcript (though if you don't have a Medscape account, you can't read beyond the first page).

Dr. Cheson's big theme seems to be that, while there are reports of studies involving traditional chemotherapies (including R-CHOP and Bendamustine), the real excitement is from newer, non-chemo agents. He seems especially high on Ibrutinib, and mentions several studies. He also discusses briefly some Kinase inhibitors.

It seems like CLL (Chronic Lymphocytic Leukemia) is the big winner at ASH this year, with a bunch of important and exciting studies being discussed (Dr. Jeff Sharman addressed these in his excellent blog about 10 days ago).

Unfortunately, Dr. Cheson doesn't devote a lot of time to Follicular Lymphoma (I guess I found more to be excited about there than he did). He does mention Rituxan maintenance, though reluctantly ("Maintenance won't seem to go away....I'm not a big fan....").

 The video is a little under 9 minutes, but worth it, even for a Follicular Lymphoma patient, just to see how excited he is about going to ASH. One quote from him kind of sums it up for me: "Great new drugs which will be changing the landscape of Non-Hodgkin's Lymphoma."

So sayeth the Rock Star.

Sunday, November 24, 2013

ASH: The Psychological Effects of Blood Cancer

OK, another paper from ASH -- this one not focused on treatment, but on its long-term after effects.

The paper is called "Psychosocial Factors and Impact Of Cancer In British Long-Term Haematological Cancer Survivors," and it looks at the psychological (rather than the physical) effects of cancer, and how being a long-term survivor affects Quality of Life.

The study looked at 718 long-term (that is 5+ years) survivors of a variety of blood cancers, including 128 Follicular Lymphoma survivors. The researchers were particularly interested in "psychological distress (depression, anxiety), functioning, and fatigue" in this group, and how that compared to the general population. The study accounted for a number of different factors that would impact how people felt.

They found that the blood cancer survivors had a worse Quality of Life than the general population, with 15% at a distress level that would make them clinically depressed, 18% with high fatigue, and 10% with moderate to severe impairment in functioning. Interestingly, higher positive scores were obtained by the Acute Leukemia patients over Lymphoma patients, and lower positive scores were obtained by patients who were Caucasian, had high education levels, did not have a partner, were depressed, and didn't have much social support. (The low scores for lack of partner and social support make sense. I guess the higher education level does, too -- maybe more apt to spend all day looking up cancer information online and not liking what we see? Not sure about being Caucasian or having lymphoma. Interesting.)

The overall results are not terribly surprising. I'm sure they are even higher among people who are survivors of less than 5 years, since that magical 5 year mark means that most cancer patients are fairly safe from relapse. (Not so much for most Follicular Lymphoma survivors, of course, though there are certainly some very long-term survivors who might dare call themselves cured.

The study brings up two questions for me in particular.

The first has to do with health care availability and its effects on Quality of Life. The paper looks at British patients only; I wonder if their Quality of Life is better knowing that they will have access to health care if they relapse. In other words, would Americans taking the same survey be more likely to be depressed, knowing that they may not be covered, or that they have lost coverage? I'm aware that the law has changed now to eliminate denial for pre-existing conditions, but with so much uncertainty surrounding the ACA, I wonder if that is affecting log-term survivors. And I wonder if any other cultural factors would influence the way the results played out in the U.S.

I also wonder how things differ among patients with different types of lymphoma. Obviously, there are physical differences between indolent and aggressive lymphomas, but I wonder what the psychological differences are, too. Every now and then, I read exchanges between patients of the two types about who has it worse -- the one that is curable but aggressive, with more toxic treatments, or the one that is not curable but slower growing, with a potentially less disruptive quality of life, and the potential to transform? (As an indolent lymphoma patient, I have a harder time representing the concerns of the aggressive lymphoma patients, because I haven't lived through their fears.)

I tend to think cancer sucks either way, and neither of us has it very good. Fears linger, even after a successful treatment, whether the doctor calls "Cure" or not. And cancer also hardens some us, too, whether it's aggressive or indolent.

That's the study I'd really like to see: the psychological affects on long-term lymphoma survivors, and their effect on quality of life. Not so we can lord it over one another and say, "See, I told you we had it worse," but more because I'd like to see more of a dialogue on how it's bad for all of us, and more importantly, how we can help each other out.

The conclusion of the study is this: "The impact of cancer on survivors’ lives is influenced by a variety of factors. By using a simple means of screening for medical comorbidity, depression and fatigue the group that needs most support could be identified early, allowing appropriate interventions to improve QOL-related measures and promote well-being by addressing both negative and positive impact of cancer."

Wouldn't it be great to be able identify early the people who will need the most help? The best thing I ever did for myself as a cancer patient was to find a group online who was supportive, knowledgeable, and encouraging. Having them there has been a major factor in my own Quality of Life. It would wonderful if others were able to find that, too.

Wednesday, November 20, 2013

ASH: Why Revlimid + Rituxan Works (Maybe)

 Another interesting paper to be delivered at ASH in a few weeks: "Correlative Analysis and Clinical Update Of a Phase II Study Using Lenalidomide and Rituximab In Patients With Indolent Non-Hodgkin Lymphoma," by researchers at UC-Davis.

This study looks at the combination of Revlimid and Rituxan. Revlimid is also known as Lenalidomide, which is how this paper refers to it. However, the combination is often known as R + R, or R2, or R squared, so I'm going with Revlimid, because then I can say R + R and not have to type Lenalidomide over and over because I'm both lazy and a horrible typist.

Anyway, the study provides an update on a phase 2 study of patients using R + R, but goes a little farther by also providing an analysis of what's going on in the body to give some hint as to how and why R + R works. There are several trials studying this combination, including one reported on last month that showed that Revlimid might help Follicular Lymphoma patients who have become resistant to Rituxan. But, as these researchers note, there's still little sense of why it works. Knowing why might help identify patients for whom the treatment will work best.

First, the straight numbers: It's aphase 2 trial, so there were a relatively small number of patients involved (just 30 who had been treated previously with Rituxan, with 22 of those being Follicular Lymphoma patients, and another 15 who had not received any treatment. So 45 in total.

Results: for those who had been previously treated, the Overall Response Rate was 74%, including 12 patients 44% who a Complete Response; 3 of those CRs lasted for more than 4 years. Of the previously untreated patients, the Overall Response rate was 92%, with 42% reaching a Complete Response.

Those numbers are fairly well in line with previous reports on R + R for Follicular Lymphoma patients, which is great. I expect there will be a phase 3 trial at some point.

The second part of it all was what made things so interesting. To try to figure out why the combination worked, they took blood samples and measured levels of cytokines in the blood before treatment, then at 15 days after receiving the Revlimid (and before receiving the Rituxan), and then at 30 days and 60 days.

Now, cytokines are a fairly large group of substances that do a bunch of things in the body, mostly signaling other things that they should get to work. So by measuring levels of particular cytokines in the blood, they were hoping to see if certain activities were being signaled to begin, and thus giving them some sense of how Revlimid works.

They measured for 10 different cytokines that are usually associated with immune response in some way; basically, they signal the body to defend itself. They found that six of them didn't respond in any significant way, but four other responded big time, particularly at Day 15, before Rituxan was given.

I'm not sure the specifics really matter, but these are the substances that increased so much:

  • IFN-y, or Interferon Gamma, which stops viruses from multiplying, but which also stimulates the immune system to act.
  • GM-CSF, or Granulocyte Macrophage Colony-Stimulating Factor, which encourages white blood cells to grow.
  • CXCL10, or C-X-C Motif Chemokine 10, which binds to cells to help T cells and Natural Killer cells find their targets.
  • And IL-2, or Interleukin 2, which helps to keep white blood cells in check, and helps the body figure out which cells belong there and which should be attacked.
As I said, for our purposes, the specific substances and the things they do probably don't matter much. What does matter is that the researchers found them, and can begin to consider the significance of them.

What also seems especially significant to me are two things:
First, these substances were especially present in the patients who achieved a Complete Response.
Second, the levels for these substances went up before Rituxan was given, so they might say a lot about Revlimid, rather than the combination. But that doesn't mean the combination isn't great, only that these particular substances increased with Revlimid. That might very well have prepped the lymphoma cells for the Rituxan, which is why the combination works so well.

And the combination does seem to work, at least for a specific group of patients. It will be interesting to see what a larger phase 3 trial ends up with.


Monday, November 18, 2013

ASH: Rituxan vs. Watching and Waiting

Another interesting abstract from ASH: "Frontline Rituximab Monotherapy Induction Versus a Watch and Wait Approach For Asymptomatic Advanced Stage Follicular Lymphoma: A Cost-Effectiveness Analysis," from several Canadian researchers. The whole "do I treat or do I wait?" debate has been going on for a while, and we don't have a definitive answer. This paper provides another perspective (though, not, I would argue, a definitive answer.)

I am, of course, a watch-and-waiter, so my bias tends to be toward this approach, if it makes sense medically and emotionally for the patient. The argument I received for watching and waiting is essentially the same that most patients hear: starting treatment right away has not been shown to increase overall survival. If there are a limited number of treatments available to Follicular Lymphoma patients, it makes sense to hold off for as long as possible before starting to chip away at that list. Also, if watching and waiting works, there's no sense in starting a treatment that could potentially result in side effects, even if they are minimal ("Do no harm," as Dr. R puts it -- choose the treatment that will give the most benefit with the least damage.)

The authors of this paper take a different look at this controversy, focusing on cost. Now, watch and wait also has that cost advantage: no treatment = no outlay. But they look at this from a different angle.

They note that the studies that have looked at watching and waiting vs. treatment all looked at some form of chemotherapy as the treatment being compared. None looked at Rituxan as an immediate first treatment. They found that a study from 2010 showed that while there was no overall survival benefit to Rituxan instead of W & W, there was a benefit in Time to Initiation of Next Treatment. In other words, Watch and Waiters needed to be treated sooner than those who took Rituxan.

The researchers developed a hypothetical model, using data from published studies. Essentially, they created fake 60 year old patients (yes, I know "fake" is a loaded term, but I also know that not all Folliuclar Lymphoma patients are 60 years old) and ran a model of what was likely to happen to them over the course of several years. They looked at the patient in 6 month intervals: based on published data about FL patients, and various median times to treatment, what is likely to happen 6 months after diagnosis? Would they need treatment? And after 6 more months, what would happen? And six months after that?

Based on this hypothetical model, they determined when these patients would likely need a first treatment, a second treatment, Rituxan Maintenance, salvage treatment, palliative care, etc -- basically running through their entire post-diagnosis lives. They ran the model with patients who began by watching and waiting, and who began by getting Rituxan right away. All of the patients received Bendamutine + Rituxan, then Rituxan Maintenance, with a maximum of 3 different treatments. Overall, they ran the model on 10,000 patients. They focused on how much all of that care would cost, based on actual Canadian health care system figures.

The results showed very little difference in Overall Survival, as was the case with other studies (and considering the data was based on actual studies, it is to be expected). So there is no arguing that one is better than the other in terms of effectiveness.

However, because the Rituxan patients required more time until treatment, the overall average monetary cost was lower for them: $59,061 for the Rituxan patients, and $74,531 for the Watch and Waiters. They argue that there is a lot of money being spent for no real benefit.

This is certainly one more variable to consider in choosing between the two strategies. While it is a simulation, it's based on data from actual patients, which does lend it some credibility. And I'm certainly in favor of reducing costs, as long as care is not comprimised.

It will be interesting to see what the reaction is for this one. I don't think treatment strategies would change based just on cost alone (that doesn't seem to be an issue right now, anyway), though it could be one more factor that tips the scales for some individual doctors in making a recommendation to patients. I think any effects from this are going to be pretty subtle.

Thursday, November 14, 2013


A quick break from all of that good ASH Follicular Lymphoma news:

Yesterday, the FDA announced that it has granted accelerated approval for Ibrutinib for Mantle Cell Lymphoma.

The accelerated designation came because the approval was based on results from a phase 2 clinical trial, rather than the usual phase 3 trial, which would have involved a wider pool patients. The results were certainly impressive: a 68% overall response rate, with 21% achieving a complete response. The response was decently long-lasting, with a median of 17.5 months.

Ibrutinib is a kinase inhibitor, a funky new class of treatments that targets kinases, which are enzymes that act to do things like phosphorylation, which is a process that I don't feel like looking up right now and describing. Let's just say that kinases work to make some complex things happen within cells, including some that encourage the growth of cancer. A kinases inhibitor like Ibrutinib stops those things from happening. (What more do you need to know?)

Ibrutinib is still not approved for Follicular Lymphoma, though a trial is currently under way that looks at Ibrutinib in Follicular Lymphoma patients who had already received a different treatment. Another small study showed that Ibrutinib works very well with R-CHOP, achieving a 100% response rate in 15 patients. I think there are others, too. As far as I can tell, there's nothing at ASH this year reporting on any Ibrutinib studies for Follicular Lymphoma.

So, not directly good news for Follicular Lymphoma, but I like hearing that treatment under consideration for FL is doing well elsewhere. There's no guarantee it will work for Follicular Lymphoma, of course, but I still like to hear those success stories.

More ASH stuff coming up.
Bruton's tyrosine kinase (BTK) inhibitor

Monday, November 11, 2013

ASH: Rituxan Maintenance for Follicular Lymphoma

Sometimes ASH or ASCO or some other lymphoma-nerd conference is kind of a dud -- nothing really new or exciting to be discussed (at least, nothing I find exciting, which is what really matters).

This year's ASH conference is an exception. There's some good stuff that's going to come out of it, and as we get closer to the actual conference, we're going to see lots of press releases from research centers and drug manufacturers touting the good things that they reported on. I try not to get too optimistic about things. I'm all about hope, but hope, by definition, always contains just a little bit of doubt. If we were really sure of something, we wouldn't need to hope.

So read everything I say as optimistic realism.


I predict that this particular paper is going to get a whole lot of discussion in the weeks ahead. It's called "Updated 6 Year Follow-Up Of The PRIMA Study Confirms The Benefit Of 2-Year Rituximab Maintenance In Follicular Lymphoma Patients Responding To Frontline Immunochemotherapy." The study is being led by Dr. Gilles Salles from Lyon, France. At the conference, this session is being held in La Nouvelle Ballroom AB at the Ernest N. Morial Convention Center. I've never been to this Convention Center, but I've been to enough conferences to know that the "ballroom" talks, especially when the ones that they take out the room divider for (it's in ballroom "AB," not "A" or "B"), are expected to attract a whole bunch of people.

Not surprising, given the topic -- Rituxan Maintenance. The PRIMA study (it stands for Primary RItuximab and MAintentance) is the major study of Rituxan Maintenance, and it is taking place in mostly European Study Centers (over 200 different hospitals and research centers in 25 countries). As the title of the paper indicates, it has been going on for almost 10 years now.

Here are the basics of the PRIMA study:  It looked at 1217 Follicular Lymphoma patients who were given one of three chemotherapies along with Rituxan (The chemos were CHOP, CVP, or FCM, which is a Fludarabine combo).  Of those patients, 1019 has a partial or complete response to the chemo + Rituxan combo. These were assigned to one of two arms: 505 patients were given Rituxan Maintenance; 519 got no further immediate treatment.  The R-Maintenance consisted of a dose of Rituxan every 8 weeks for 2 years. The first major update for the study was published in The Lancet (a major British medical journal) in 2010: after 36 months, Progression Free Survival for the R-Maintenance group was 74.9%; for the other group, it was 57.6%.  The conclusion: R-Maintenance works.

Now, the important thing to remember is that PRIMA is not the only study of R-Maintenance (though I believe it is the largest).  Other studies have shown less success, or at least less dramatic benefit. Lymphoma Rock Star Dr. Bruce Cheson offered a nice summary of some of these studies after last year's ASH conference. The basic complaint: still not enough evidence that the large number of doses of Rituxan is worth the expense, since there appears to be little Overall Survival benefit to R-Maintenance.

So now we have this year's ASH presentation. It reports on those same 1019 patients, but with three additional years of data. Here's the upshot: After 73 months (a little over 6 years), the Progression Free Survival rate for the R-Maintenance group is 59.2%, and for the other group, 42.7%. That's down some from 3 years ago, but that's certainly to be expected. The key number is the difference between the two groups. It has stayed roughly the same -- about a 17% difference. And the difference was even bigger for older patients (doesn't define what that means), female patients, and those with lower FLIPI scores.

Three other important points: 1) there seems to be no difference in the two groups for rate of transformation (which seems really small, though I need to look into that more); 2) there is no difference in Overall Survival (around 88% after 6 years); and 3) when patients did need a second treatment, there was no difference in the effectiveness of that treatment (in other words, the R-Maintenance didn't make the treatments less effective).

It will be interesting to see how people respond to this paper. It certainly does make a case for the effectiveness of R-Maintenance after chemo. But, as Dr. Cheson pointed out last year, there are some other studies that call into question whether r not it's worth it. My guess is the lymphoma community is going to be split: those who already believe that R-Maintenance is the way to go will praise it; skeptics will call on us to wait until some of those other studies (like the RESORT study) also present longer-term results, for comparison.

Or, maybe this will be enough, and we'll have some consensus that R-Maintenance is the way to go. (History, however, suggests that we will still be debating this next year. After all, the superior numbers for Bendamustine haven't stopped lots of oncologists from preferring R-CHOP as a first treatment.)

I'm kind of looking forward to what happens next.

I'll have something else from ASH in a few more days.

Saturday, November 9, 2013

ASH Follicular Lymphoma Abstracts are Here!

It's the most wonderful time of the year!

(For a cancer nerd!)

The abstracts for the annual American Society of Hematology conference are available online.

 The ASH conference will be held in New Orleans this year from December 7-10. (I have some very fond memories of a trip to New Orleans when my wife and I were first married. Shrimp and oyster po' boys. The St. Charles street car. Cross-dressers singing Cher songs....stories for another time.....)

Anyway, the ASH conference is often when some of the most interesting research about Follicular Lymphoma (and other blood diseases) makes its debut. In a quick search, I found 169 results for "Follicular Lymphoma," and I'll spend the next week or so looking through them to see what's interesting.

One that stands out right away: "Follicular Lymphoma In Young Adults: Clinical Characteristics and Early Treatment Outcomes." I consider myself still young, especially in Follicular Lymphoma terms, given that the median age of those diagnosed is about 67. Alas, "young adults" in this sense means those under 40. I was 40 years and 6 months when I was diagnosed. But I'm young at heart, so I'm interested in what they have to say.

The study looked at 410 patients who were newly diagnosed with FL; 55 of them were under 40, and the rest were between 40 and 65 (referred to as "older patients," which I'm trying hard not to be offended by). The researchers were interested in how different the lymphoma was -- if there were physical differences, or different outcomes.

They found a few differences: 10 year Overall Survival for the Young Adult group was 89.3%; for the older folks, it was 74.2%. Now, Overall Survival measures death from any cause, whether disease-related or being hit by a runaway streetcar in New Orleans. So it's probably not too surprising that a 39 year ols has a better 10 year survival chance than a 65 year old.

So they measured lymphoma-related survival, too, and found a lower probability of death in the young folks (4%) than in the older folks (15.3%). However, this was not found to be statistically significant (which means they probably didn't have enough patients to look at to really find a trend that they could be confident about).

And here's another fascinating tidbit: the Watch-and-Waiters did much better than those who had treatment right away. (But don't read too much into that. If anything, it just validates that W & W is still an OK choice; it doen't mean it's right for everyone.)

Their conclusion: the physical characteristics of Follicular Lymphoma are pretty much the same, no matter the age of the patient. But younger patients seemed to have a better Overall Survival, and it's going to take more research to figure out why that is true.

Interesting stuff. I'll keep reading and post more soon. (And try to provide a warning for why we should be optimistic, but not too excited, about positive stories from ASH.)

Thursday, November 7, 2013

Dr. Cheson on Follicular Lymphoma

Apparently, Matt Lauer and Al Roker got live prostate exams on the Today Show this morning, to raise awareness during Prostate Cancer Month. This is a link from a news story yesterday that said it was going to happen.  I'm not including a link to the actual show, because I don't really care to watch Al Roker get a prostate exam. Besides, "I'd rather watch Al Roker get a prostate exam" sounds too much like a Jay Leno punchline.

There -- I've done my part to promote prostate cancer awareness.


Lymphoma Rock Star Dr. Bruce Cheson gives us the State of the Art in managing Follicular Lymphoma, in an interview with Clinical Oncology News. Dr. Cheson is Head of Hematology at Georgetown University Hospital in DC, and he's a very visible expert on Follicular Lymphoma, appearing online to explain things clearly. (And frankly, I need something from someone like him, given my last couple of posts. This interview comes at a good time.)

It's not a long interview, so I'll give you what are for me the highlights:

Dr. Cheson was asked the difference between FLIPI and FLIP-2, and how a score influences his treatment decisions. FLIPI stands for Follicular Lymphoma International Prognostic Index, and it was designed to help doctors gauge patient outcomes, and thus how aggressively to treat. It's a funny index; it's best to think of it as an estimation of where you are, not a prediction of what will happen. The difference between the two is FLIP-2 is a more recent creation, and takes into account he difference that Rituxan has made on treatment. What the FLIPI indexes will not tell you, though, is when to treat.

For that decision, Dr. Cheson consults the GELF criteria (the name comes from the Groupe d’étude des Lymphomes Folliculaires, a French study group for Follicular Lymphoma). GELF lays out some of the physical properties that might make it a good time to treat (things like lymph node size and some blood counts).

The "when" question, of course, assumes that treatment isn't necessary immediately, which again brings up the issue of Watch and Wait. Dr. Cheson gives his take on the W & W controversy, one that I agree with. First off, he wisely mentions that importance of taking psychological and emotional factors into consideration. Physical factors aside, some patients want to be treated right away. Others, conversely, feel better knowing they can hold off treatment. GELFs and FLIPIs mean nothing until the doctor understands how it affects the patient emotionally.

From there, Dr. Cheson reviews the research on Watching and Waiting. His conclusion? He still uses it for patients in certain situations. 

Dr. Cheson closes with a discussion of curability, mostly with regards to Stage I and II disease, which are diagnosed only about 15% of the time. But he has some thoughts on the curability of later stage disease, too, that are worth considering. (No, Follicular Lymphoma is still not curable, but Dr. Sheson suggests we might re-think what that means in the long term.)

Overall, it's a nice summary of where we are with Follicular Lymphoma, from a well-known expert. There's a part 2 for next month, with his thoughts on front-line treatments and maintenance therapy. Looking forward to that one.