Friday, August 28, 2015

Lymphoma Patient Survey

Patients Against Lymphoma (PAL), the group that runs the website, is conducting a survey of lymphoma patients.

The purpose of the survey is "to understand the status, interests, and concerns of the online lymphoma community." PAL will use the results to continue to improve the already excellent The results "will also help inform clinical practice and research."

The survey only takes 5-10 minutes to complete. If you take it (and I really hope you will), be sure to read the introduction, so you are fully informed about the survey. (I know you readers have a thing for being fully informed....)

You can find the PAL survey here

Maybe we can't all do something like join a clinical trial, but this is an easy way to help shape our future as lymphoma patients, even in a small way.

I know the folks behind the survey appreciate your time and help.

Tuesday, August 25, 2015

Obinutuzumab in Follicular Lymphoma

The Journal of Clinical Oncology has an early release version for an article called "Randomized Phase II Trial Comparing Obinutuzumab (GA101) With Rituximab in Patients With Relapsed CD20+ Indolent B-Cell Non-Hodgkin Lymphoma: Final Analysis of the GAUSS Study."As the title suggests, this is a report from the phase II clinical trial that compared Rituxan and Obinutuzumab.

A little background first. Obinutuzumab, like Rituxan, is a monoclonal antibody that targets CD20, a protein on the surface of Follicular Lymphoma cells (and other lymphoma cells). There have been several attempts to find a monoclonal antibody that can do a better job than Rituxan, but so far, there's no clear winner (and this study seems to show that Obinutuzumab isn't a big improvement on Rituxan either).

Obinutuzumab (also known as GA101 in the past, and Gazyva in the future) is different from Rituxan in a couple of ways. First, it is humanized, formed from human cells (Rituxan comes from mouse cells), so the thought was that it would cause fewer allergic reactions. Second, it is glycoengineered, which means they have had sugar molecules attached to them in a way that makes them more effective. (You can find out more about that process from this fun little video involving an antibody beauty contest, a mouse with an umbrella, and a five year old girl dressed like a ballerina with dinosaurs on her dress.) Obinutuzumab has been designated as a Breakthrough Therapy by the FDA for CLL. But, again, it seems less effective on Follicular Lymphoma.

The phase II study involved 175 patients with relapsed CD20-positive indolent lymphoma; the great majority of them (149) had Follicular Lymphoma. All patients had already had a response to a treatment that contained Rituxan. Half the patients in the study received Obinutuzumaband half received Rituxan, both of them once a week for four weeks.

For the FL patients, the good news was that more of them had a response to Obinutuzumab -- 44%, while only 33% of the Rituxan patients had a response. When an independent panel looked at the results, the difference was even bigger: 44% responded to Obinutuzuma, but only 26% to Rituxan. So by that measure, Obinutuzumab does seem more effective.

The bad news, though, was in how effective it was for individual patients who did have a response -- there was no real difference between the two groups in their Progression Free Survival. In other words, patients in both groups went the same amount of time before the disease came back. Not much difference in safety between the two groups, except that the Obinutuzumab group had more infusion-related reactions and cough.

The authors of the article believe the higher Overall Response Rate is enough to justify a phase III clinical trial.

What this means, of course, is that Obinutuzumab may not be the best choice for this population -- Follicular Lymphoma patients who had already had treatment that contained Rituxan. There are other trials out there, including one that was reported at ASCO this year, from the Gadolin trial, which found significant improvement in PFS when Obinutuzumab was added to Bendamustine (versus Bendamustine on its own).

So we won't give up on Obinutuzumab just yet. It's a good reminder that all of this is going to take time, and our job is to stay informed and support Follicular Lymphoma research in any way we can.

Sunday, August 23, 2015

The Biology of Lymphoma

Big weekend in our family -- my wife and I drove our oldest child off to college, and left him there to begin the rest of his life. We're sad to see him far away from us, but excited to see what comes next in his life. He was good enough to call us tonight, and let us know that he's making friends and having fun. He starts classes in a week, and getting to know his new school and his new city in the meantime.

Another milestone for me as a cancer patient, too. When I was diagnosed, I hoped that I'd be around long enough to see this. Very happy to be here for it.


It's exciting to think about all that's come before, and how it has built up to where we are now, whether its a child or a cancer treatment.

OK, that was an awkward transition, but here's the cancer portion of this blog entry:

The good folks at Patient Power have a fairly recent video with some commentary from the European Hematology Association meeting that took place earlier this summer. The video is called "How can we apply our growing understanding of the biology of cancer?" and it features a short (less than 3 minute) conversation with Dr. Andrew Davies from the University of Southampton in the UK.

Dr. Davies discusses his excitement over some of the recent discoveries in the biology of lymphoma, and how new treatments (like kinase inhibitors and BTK inhibitors) are being developed as a result of this new knowledge. He makes some interesting points about where we go from here, and the partnership that researchers, clinicians, and patients have to create in order for it all to happen -- that means participating in clinical trials so we can see if they work, and how.

It's a short video, but an important message.

Tuesday, August 18, 2015

New Info on Transformation in Follicular Lymphoma

The most recent issue of the journal Blood includes an important article called "Outcomes of Transformed Follicular Lymphoma in the Modern Era: A Report from the National LymphoCare Study (NLCS)." Transformation, for those of you who are new to this, is the process that sometimes happens to Follicular Lymphoma, where it transforms from a nice, slow-growing indolent disease to a not nice, fast-growing aggressive disease.

The article shows us the most up-to-date information we have on transformation in Follicular Lymphoma -- the thing that many of us fear most about our disease.

The reason we fear transformation so much is that it has always had a low survival rate -- just 1 or 2 years. So let's get to the first bit of good news from this article -- the Overall Survival rate for patients with transformed FL is about 5 years. That's a darn good jump.

So now that the most important news is out there, let's step back a little and look at the study. It is part of the very large National LymphoCare Study, which looked at data from almost 2700 FL patients from 2004 to 2007. The study is observational -- they didn't give any specific treatment, but instead kept track of what happened to all of these patients and how well they did.

For this study on transformation, researchers looked at 2652 patients, and followed up with them for more than 6 years. They found that 14.3% of the patients had transformed.

(A quick comment on this: 14% is on the low end of the estimates that have been thrown out there. I've seen numbers in a bunch of places that say anywhere from 12% to 50% of FL patients will transform. So the 14% number is comforting, though I'm not convinced that it's the last word on transformation rates.)

Another interesting bit of information: patients who received treatment right away had a transformation rate of 13.4%. Patients who were first observed (that is, did some watching and waiting for more than 90 days) had a transformation rate of 17.8%.

(As a watch-and-waiter, I should have a reaction to that number, and I do. But it's a pretty mild reaction. I don't see a 4% difference as all that significant, though I think it is statistically significant. It's still better than the 30% or 50% rate I see other places.)

Interestingly, though, while the transformation rate was a little higher for patients who were observed, there was no difference between the two groups in Overall Survival. So a watch-and-waiter might have a little higher chance of transforming, but the outcome wasn't any different than someone who received treatment right away.

Also interesting -- patients who received only chemotherapy, without Rituxan (that is, CVP or CHOP instead of R-CVP or R-CHOP) had a transformation rate of 18.3%, even higher than the watch-and-waiters. Fascinating.

There's more in the article, and it's worth a look, if you like that kind of thing.

So what does all of this mean?

Well, in my humble opinion, the increase in Overall Survival from 1 or 2 years to 5 years is a big deal. Given when the information was collected (2004 to 2007), it seems like maybe Rituxan is responsible for that jump (?). That's completely speculation from a non-expert, but that's about the time Rituxan use was really in full swing.

And while I said this was the most up-to-date information we have about transformation, it's important to look at those dates again -- it was collected almost 10 years ago. That doesn't make it less valid. Collection ended in 2007, then there was a follow-up period of almost 7 years (2013-2014), then the article was written and peer reviewed, so here we are in August 2015. That's a carefully researched and written article, and we should be grateful for that. But it also means that it doesn't account for any treatments that have become available more recently -- Bendamustine, Revlemid and R-squared, RadioImmuno Therapy, Ibrutinib, Idelalisib, all kinds of inhibitors. We won't know for a while what kind of long-term effect these treatments might have on transformation, but I'm willing to put my hope into thinking the effect will be positive. Things could be even better than we think right now.

And finally, as for the various statistics on rates of transformation for each initial treatment type -- the differences seem so slight to me (4 or 5% between the best and the worst) that I can't imagine making a treatment decision based on that. And no one is suggesting we should. I certainly don't regret my decision to watch-and-wait, and neither should you -- or whatever decision you made back then.

The bottom line is, the study gives us some reason to be optimistic about transformation. It's still a scary thing, but it's looking better -- lower transformation rates, and higher survival rates. So let's focus on that and hope that future studies bring us even better news.

Saturday, August 15, 2015

More Red Sox Lymphoma

Yesterday afternoon, John Farrell announced that he has lymphoma.

Farrell is the manager of the Boston Red Sox baseball team (my beloved Red Sox). He's the third member of the Red Sox family to announce a lymphoma diagnosis. The other two are pitcher Jon Lester, my hero (diagnosed in 2006), and outgoing team president Larry Lucchino (diagnosed in 1985, before he was with the Red Sox).

Farrell didn't say what type of lymphoma he had, but he did give a few other details: he felt a twinge when he picked up a suitcase, and saw a doctor who found that he has a hernia. During the surgery, the lymphoma was discovered. It is stage 1, localized, treatable, and "very curable." He will start chemotherapy soon, and receive chemo for 9 weeks.  Chemo is, he said, the only option. He also said he was asymptomatic, with no B symptoms (night sweats, fatigue, or weight loss).

It doesn't really matter what type he has, but a cancer nerd can't help but speculate. It certainly isn't Follicular Lymphoma, based on what he says -- curable, with chemo being the only option. Makes me think it's something aggressive, and not some other indolent type. If that's the case, he is, as he says, a lucky man, having caught it when it is stage 1, localized, and before any B symptoms.

He said he was very surprised, and that the last few days have been "surreal." I think we all know that feeling, especially those of us who didn't have any other symptoms. Reading about his reaction brought back some memories.

It brings back some memories of Jon Lester, too, and the role he played for me early on. I've told the story before -- Lester was diagnosed in 2006 and came back the next year to win the deciding game of the World Series for the Red Sox. When I was diagnosed, my son Peter, a big Red Sox fan, felt a lot better about my diagnosis when I reminded him that Lester also had NHL (it wasn't Follicular Lymphoma, but my 10 year old didn't need to know that).

Lester has done well since then (health-wise -- he's playing for the Chicago Cubs now, and seems to be a little uneven this season. 8 wins and 8 losses, but his strikeouts per game almost as high as his best seasons. Yes, I still follow how he's doing).

And I have faith that John Farrell will also do well. He's going to get great care at Massachusetts General Hospital in Boston. Lester thinks Farrell will do well, too.

I wish him much luck in his journey.


I'm adding a little something, a few hours after I wrote the stuff above:

A physician posted his take on John Farrell's diagnosis, to a blog called Blue Bird Banter, which focuses on the Toronto Blue Jays, the team Farrell managed before the Red Sox. I think it's a good post (and not only because this physician goes by the name SuckaMD -- nice shout out to Run-DMC).

Anyway, SuckaMD gives a nice quick breakdown on what lymphoma is, and speculates that Farrell has DLBCL, and is probably getting R-CHOP. (I figured it was aggressive, not indolent, too -- nice to get some back-up from the medical community). He also speculates that, given how early it was caught, Farrell has over a 90% chance of being cured. I'm not a physician, so I wouldn't make that kind of call, but SuckaMD's reasoning certainly seems right.

So if you're interested, check out what he has to say. Again, it doesn't really matter what type of lymphoma he has -- only that he's getting treated. But it's still interesting to speculate. It's what Cancer Nerds do.


One more addition on 8/18: John Farrell starts chemo today, and he will be accompanied by his friend Terry Francona. The two of them were teammates years ago, and then wprked together as coaches. When Francona was hired as manager of the Red Sox, he brought Farrell along as one of his coaches. Francona is now manager of the Cleveland Indians, who are in Boston to play the Red Sox. So Francona will be there for his friend when he starts chemo.

Terry Francona was manager of the Red Sox when I was diagnosed, and someone asked him to write a letter of encouragement to my kids. I still have the letter.

Nice guy. We should all have a friend like him.

Thursday, August 13, 2015

Make Love, Not War (on Cancer)

Nice article a few days ago from Betsy de Parry, Lymphoma Rock Star and patient advocate. (I've discussed Betsy's writing before. She is the author of Adventures in Cancerland, in which she describes her experience with Follicular Lymphoma and RadioImmuno Therapy -- she's been cancer free since 2002. I also like her because we share a family name from a few generations back, so I like to think we are cousins.)

Anyway, Betsy has been writing occasional posts for mCancerTalk, the blog for the University of Michigan's Comprehensive Cancer Center, where she received treatment. Her latest post is called "War as a Metaphor for Cancer Can Be Relieved of Duty." I don't want to give too much away, because it's a really well-written article, and I want you to read the whole thing.

But Betsy's basic point is that comparing cancer to a war, and using other language like that (battle, fight, enemy within, etc.) does more harm than good. Again, take a look at the article yourself to see why she thinks so.

I will admit, I do sometimes use that kind of language. I remember it was really useful a few years ago. I am very lucky that I have a job that lets me choose some of the projects I want to work on (certainly not all, but some). I used to enjoy saying No to some of them with, "Sorry, I can't help you with that. I'm busy battling cancer...."

But really, there are some days when it feels like a battle is what is called for, and a warrior is what I need to be. But, as Betsy says, sometimes that's not so good. (Again I say -- read the article.)

The bigger point here is that the language we use really matters. For some people, being a warrior in a battle is important (even Betsy says so). But even small things matter. I remember writing a long time ago about a conversation I had with someone about this. Given who the person was, I think it was probably within a year after I was diagnosed. This friend had been talking to another friend, who had been diagnosed with breast cancer was organizing a fundraising team. My friend had apparently been talking with her about what to call cancer patients.

My friend told me, "If you've had cancer for more than 5 years, you're a cancer survivor. If it's less than 5 years, you're a cancer victim." I had no idea where she got those terms from, and I still don't, but I knew one thing then and I know it now -- I'm no damn victim. And I'll never be. For me, being a  victim would mean just giving in to my cancer and accepting whatever happens to me. I just can't be that person.

Does that make me a warrior instead? Maybe. I can still feel the physical response I had when I was told I was a victim. Sure felt like I wanted to fight something, or someone.

I'm not that way much anymore. These days, I still fight my battle, but it's a long, slow battle -- a battle of wits. I'm not a warrior so much as a Cancer Nerd. Think Doctor Who more than Doctor Evil.

And I like calling myself a Cancer Nerd. It fits -- what else would you call someone whose main weapons are ,medical journals and a Blogger account?

More importantly, it's a name I chose, a label I gave myself that fits who I am and what I want to be.

And that's what we should all do and be.

Saturday, August 8, 2015

A More Accurate FLIPI?

Fascinating article soon to be published by Lancet Oncology: "Integration of Gene Mutations in Risk Prognostication for Patients Receiving First-Line Immunochemotherapy for Follicular Lymphoma: A Retrospective Analysis of a Prospective Clinical Trial and Validation in a Population-Based Registry."

Basically, this is all about improving FLIPI, so let's start there.

FLIPI stands for Follicular Lymphoma International Prognostic Index. It was developed by an international team of FL specialists as a way of deciding how aggressively to treat the patient by (essentially) guessing what the patient's 5 year survival will be.

I'm trying to be really careful here, as I am whenever I bring up FLIPI. It's kind of controversial, because it does pretty much make a guess, based on statistics from how FL patients have done in the past. Here is how FLIPI works -- each one of these factors gives you a point:
  • Patient is over 60 years of age
  • has stage III or IV disease
  • has five or more nodules or tumors, or more than four lymph node groups involved
  • has serum hemoglobin less than 12 g/dL
  • has elevated levels of LDH
Having 0-1 points makes you low risk; having two makes you intermediate risk; and 3 or more makes you high risk. The "risk" here is related to 5 year survival -- the higher the number, the greater the risk that you won't reach 5 years.

Let's be clear about this, though -- as says in its discussion of FLIPI,

"physicians may sometimes use FLIPI to guide treatment selection and possibly timing of treatment, but FLIPI is not predictive of outcomes in individual cases - or predictive of outcomes with specific therapies."

Having a score of 1 doesn't mean you'll necesssary live longer, and having a 5 doesn't mean you'll die in five years. This is based on statistics of how well patients did in the past -- in other words, old statistics.

There's a FLIPI-2 index, too, that used different measures and updated statistics. But it's also controversial, since it works on the same assumption -- comparing patients from the past to patients right now will allow us to make guesses about their survival. Not only are you looking at statistics from the past, you're also looking at some pretty general information. (Age, for example.)

That's where the Lancet Oncology study comes in. By looking at newer statistics and some different factors, they think they have been able to improve on FLIPI and FLIPI-2. It's the new factors that are the big change here -- their research looked at 7 different genes associated with Follicular Lymphoma, and whether they have mutated. (In case you are curious, the genes are EZH2, ARID1A, MEF2B, EP300, FOXO1, CREBBP, and CARD11.) Those genes are associated with different levels of aggression in Follicular Lymphoma.

They call the new index m7-FLIPI, and after they developed it, they tested it on a different group of patients, and found that it was a more accurate predictor of 5 year survival.

So what does all of this mean?

Well, first the positive -- no version of FLIPI will predict how well an individual patient will do, but the fact that this group has been able to work genetic mutations into a new FLIPI says a lot about where we are in understanding Follicular Lymphoma. It wasn't long ago that we had no idea what kind of influence genetic mutations had on the disease. the fact that we can now identify them and use them in a prediction model is huge in showing how far we've come. It will only get better from here, as we are able to identify more genetic influences on our disease, and figure out how to use them to treat it.

Now, the less positive. Even though it's an improvement on the old FLIPIs, it still is far from perfect -- it was accurate about three-fourths of the time, at best. 25% inaccurate is still a pretty big number. In some ways, it's not surprising -- there are so many other factors, even beyond things like age and LDH and FOXO1 mutations -- that influence how well we do, that it's going to be almost impossible to make any kind of 100% accurate prediction. Cancer is just too unpredictable, and Follicular Lymphoma seems even less predictable than others. Then there's the basic question of what value a predictor even has -- if I know I am "intermediate risk," as my FLIPI score of 2 would suggest, what does that really even matter? I was treated fairly non-aggressively, watching and waiting for two years, and then getting Rituxan. Would things have been done differently if I was a 1 or a 3 at diagnosis? Probably not.

So I'm taking the positive big picture look at all of this -- it's a nice snapshot of where we are right now, in terms of understanding Follicular Lymphoma.

And it's only going to get better.

Sunday, August 2, 2015

RRAGC Mutations in Follicular Lymphoma

The 2015 Congress of the European Hematology Association was held in Vienna in June, and I'm starting to see some of the good research that was presented there. EHA is more or less the European equivalent of ASH, the American Society for Hematology. Same goals -- to showcase research that targets blood diseases, including Follicular Lymphoma.

One of the reports I came across was a brief video (under 5 minutes) of Dr. Jessica Okosun from the Barts Cancer Institute in London, who has done a bunch of research on genetic mutations in lymphoma.

In the video, Dr. Okosun describes the research she presented at EHA, "Recurrent mTORC1-activating RRAGC Mutations in Follicular Lymphoma."

RRAGC is a gene that switches on processes that cells require. We see a lot of that lately -- researchers are understanding how all of these different switches are necessary for a cell to work normally, and how cancer happens when those cells don't turn on or turn off the way they are supposed to. As Dr. Okosun says in the video, RRAGC mutation seems to occur in about 20% of Follicular Lymphoma patients, and, from what researchers can tell, in no other types of cancer.

The RRAGC mutation is related to mTORC1 because mTORC1 signals to a cell that it is OK for it to grow. RRAGC is an important part of this pathway because it allows mTORC1 to know that there is enough amino acid in the cell to continue behaving normally. (Amino acids are building blocks of proteins.) So if there isn't enough amino acid, the RRAGC lets the mTOTC1 know that it shouldn't behave normally and grow and divide.

However, the RRAGC mutation allows the mTORC1 to skip that step of making sure it had enough amino acids to grow and divide. And so, the Follicular Lymphoma cells keep growing and dividing when they're not supposed to. And, as we unfortunately know, that's what cancer is.

As Dr. Okosun makes clear, the RRAGC mutation occurs in only a portion of Follicular Lymphoma patients, so understanding this pathway (and eventually finding a treatment that targets it) is not going to help all of us.

However, I get excited about these small pieces -- they give us another piece of the puzzle, and give researchers more to focus on.

It still amazes me that we can know so much about such tiny, tiny things going on in our bodies.