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.

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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.

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.

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.

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.

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.)

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.

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.