Wednesday, December 30, 2015

Rituxan Maintenance: Shorter is Better?

The current Journal of Clinical Oncology has the results of a study of Rituxan Maintenance in Follicular Lymphoma. In some ways, the study helps clarify the best way to use Rituxan Maintenance, though it raises some questions as well.

(We wouldn't really expect any kind of clear answer when it comes to treating Follicular Lymphoma, would we?)

The study is published in the article called "Rituximab Maintenance for a Maximum of 5 Years After Single-Agent Rituximab Induction in Follicular Lymphoma: Results of the Randomized Controlled Phase III Trial SAKK 35/0." Medical journal articles are pretty good about using straightforward titles, and this one is no different:

The article reports the results of a phase III clinical trial that looked at short-term and long-term use of Rituxan Maintenance after Rituxan induction therapy. In other words, patients were first given Rituxan for four weeks, and then if it seemed to work, they were split into two groups, with some getting Rituxan Maintenance every two months for 4 doses (or 8 months), and some getting it every two months for up to 5 years (or until they had an event). The measurement here was Event Free Survival (EFS), which is a little less common than many FL trials, which often use Progression Free Survival (which measures the disease getting worse) or Overall Survival (which measures death from any cause). EFS is a little broader, and the "events" can include death or disease progression, but also things like a secondary cancer, unacceptable toxicity, or using other treatments related to cancer.

The authors say that, while there are lots of studies that look at Rituxan Maintenance, those studies use lots of different time periods. Their aim here was to compare two different time periods directly to see which one worked best.

The plan had been to stop the study at about 5 years, with the expectation that there would have been 99 events to count. However, they stopped when they had reached 95 events, because the events stopped coming. I think that's good news -- both types of Maintenance seemed to work well.

In the end, though, they found that longer isn't necessarily better -- there was no real difference in Event Free Survival between the two groups -- neither approach seemed better than the other. There was also no difference in Overall Survival between the two groups, though the researchers want to continue looking at data for a longer time to see if that remains true.

However, the long-term group had a Progression-Free Survival that was much longer than the short-term group. (They kind of down-play this, though it seems significant to me. It's probably because their primary measure was EFS, and because the OS was the same, so it doesn't really matter on its own.)

The researchers point out several important things in their conclusion:

First, if there is no difference in EFS or OS between the two, then short-term seems the better option. It will be less expensive and cause less toxicity.

Second, there were more patients with "adverse events" in the long-term arm than the short-term. These include things like infections, which makes sense, since Rituxan kills off the B cells that fight infections.

Finally, they point out some of the limitations of their study, including their not measuring quality of life. It is possible that, for lots of reasons, long-term Maintenance could result in lower quality of life.

So in the end, the results are mixed. If anything, the study seems to back up the idea that Rituxan Maintenance can be a good thing (though they weren't trying to prove that it is better than waiting until Rituxan is needed before giving it), and the idea that short-term Maintenance is just as good as long-term, and maybe better, if you consider the cost.

Sorry, folks -- no Big Answers here. But I still feel OK knowing that even a small piece of the puzzle is being put into place.

Friday, December 25, 2015

Merry Christmas

Today is Christmas for a large part of the world. I know that not everyone who reads the blog celebrates this day, so for those of you who do, I say Merry Christmas.

And for all of you, whether you celebrate or not, I offer another traditional greeting for the day: Peace on Earth.

It seems like more than ever, we could use some peace on our planet. For those of us with Follicular Lymphoma, or any type of cancer, we have enough inner turmoil. We don't need all of that outer turmoil, too. It won't go away just by wishing you peace, but maybe all of our good feelings will add up and make a small difference together. Just a little less turmoil in our own tiny little parts of the world.

I don't know how many of you celebrate Christmas, but I do know you come from lots of countries besides my own, and I love seeing comments that identify where you are from. It's easy to see how different we are, just from the name of a country. But it's so much easier to see how much we are the same. Every one of us has had the same experience -- being told (or having a loved one be told) that we had cancer. There isn't much worse than hearing those words, and it's not a happy thing to have in common with so many other people.

So lets all try to spend just one day thinking about all of the other things we have in common with the people we encounter today, whether we're celebrating Christmas or not. Everyone hurts in some way, whether it's from cancer or not. But everyone celebrates those small joys, too. So find some way to celebrate with them. Or, even better -- give them some reason to feel just a little spark of joy.

Contribute to some peace on earth.

Have a good day, everyone.

Sunday, December 20, 2015

ASH: Ofatumumab

Still looking at some of the research that was presented at ASH this year.

This one is called "Phase II Trial of Ofatumumab (OFA) in Previously Untreated Follicular Non-Hodgkin Lymphoma (NHL): CALGB 50901 (Alliance)."It looks at Ofatumumab as a first treatment for Follicular Lymphoma.

Ofatumumab is a lot like Rituxan -- a monoclonal antibody that targets the protein CD20 on the surface of B cells. The key difference is that Ofatumumab fully humanized. Rituxan was developed using mouse cells, but Ofatumumab was developed using human cells. The thinking is that this might cut down on some of the allergic reactions that people have when they are first given Rituxan. (I had chills and a lot of itching.)

In the ASH study, the researchers try to compare Ofatumumab to Rituxan in patients who haven't been treated yet and who have low or intermediate risk FL. Since this is a comparison to Rituxan, they were looking to show that Ofatumumab would do a better job than Rituxan, so they considered a repsonse rate below 60% to essentially be a failure, and over 80% to be a great success.

Since it was a phase II study, it was fairly small, with just 51 patients. Some received a dose of 500mg, and others 1000mg, all once a week for four weeks, and then four more times every 8 weeks. For the patients with the 1000mg dose, the Overall Response Rate was 86.7%, and 1 year Progression Free Survival was almost 100%. For the patients with the 500mg dose, the OR was 60%, and the 1 year PFS was 85.1%.

The researchers conclude that Ofatumumab was effective and well-tolerated. The side effects were not too far out of line with Rituxan. However, they also concluded that  "Activity appears to be in a range comparable to that reported with other anti-CD20 antibodies in this setting, suggesting that significant improvements in efficacy will require novel combinations." In other words, it did about as well as Rituxan, but not much better than Rituxan, so it seems unlikely to replace it. Maybe it will be used with some other treatments in ways that are more effective than Rituxan.

Ofatumumab isn't the first attempt to replace Rituxan, and so far, no monoclonal antibody has shown to be better than it. I find that fascinating. There has to be something about the mechanism of monoclonal antibodies that has a limit, which is who combining it with something else might be the way to go. we've known for a long time that Rituxan works well, and CHOP and other chemos work well, but it's when they are put together that they really shine. Research into which combinations work best to attack cancer from different angles seems to be a very effective strategy.

Ofatumumab was actually in the news for something else recently, too. In late November, the company that makes Ofatumumab announced that it was stopping a phase III trial before it was done because the early results showed that it wasn't going to be much of an improvement over Rituxan. This was a little different from the ASH study -- it compared Ofatumumab and Rituxan directly, but involved patients who had previously been treated with Rituxan. But the big picture was still the same thing -- it's hard to do better than Rituxan.

If monoclonal antibodies do have a long-term future in Follicular Lymphoma treatment,  it looks like it will be in combination with other. newer treatments.

Monday, December 14, 2015

More on CAR-T for FL

I got a nice comment on my last post (about the CAR-T study at ASH), and I thought it was worth sharing here because sometimes things get lost in the comments section. The comment is from Ben, who has had some success with CAR-T.


Hi Bob,

Thanks for covering this topic. This is the second time I am commenting on one of your posts. The first time was when you mentioned Revlimid/Rituxan, the so-called "R-Squared", as I was being treated with it.

And now you've done it again. I can provide more insight to you and anyone else reading this, as I myself am a CAR-T patient. I was infused with my "re-engineered" T cells in July, and was discharged in August after some unfortunately rather severe CRS (I needed to be in ICU for 5 days).

However, my follicular lymphoma is now in a Partial Remission (PR), with minimal activity showing in my most recent PET/CT. This is after getting minimal response from the aforementioned R-squared, and a subsequent HYPER-CVAD regimen, before entering the CAR-T trial.

We've since recommended CAR-T to another fNHL patient we learned about through a family member. He was diagnosed only a year ago, but got only a minimal response from R-CHOP and R-Bendamustine, and his lymphoma got progressively more active. He may have even started transforming.

This fellow was also infused over the summer, and now has a Complete Remission (CR), and did not have any of the CRS symptoms that I experienced. He was even able to do this as an out-patient at his facility, since his fever remained low and only lasted a couple of days.

So for anyone reading this, please know that another option exists for follicular lymphoma patients who are no longer getting good responses from their current therapies, which is of course often the nature of this disease.

I had mentioned in my first R-Squared post almost a year ago that I was considering starting a blog as you have done, and you had encouraged me to do so. I unfortunately never got around to it, but now I am re-considering. Hopefully this time I'll get around to it. I'll keep you posted...

Thanks so much for your continued coverage of current events re fNHL!


-- Ben 


 There are a few things worth mentioning here:

First, thank you, Ben, for the comment, and I hope you don't mind my highlighting it here.

Second, I think it's really valuable to hear stories from people who have actually had the treatment. I have been fortunate enough to not need treatment for several years now, so I can't talk much about any of these new treatments, so I really appreciate Ben sharing his story.

I especially appreciate him talking about the side effects he experienced. I sometimes ignore that part of the research I describe. I get so excited about results sometimes that I don't give the bad part of the research. And every treatment does have some kind of side effects. in Ben's case, it was a bad bout of CRS, which is Cytokine Release Syndrome. Basically, with CRS, T-cells release a protein called Cytokines, which can cause an inflammation response in the body. The CRS can be fairly mild, and not too dangerous, making the patient feel really horrible, but not doing much damage. But it can also be pretty severe, as it seems to have been with Ben, who was Intensive Care for a few days.

That's really important to remember (and for me to remember when I write about these things) -- every treatment has some side effects, and it's important to understand them fully.

Finally, Ben mentions blogging. It's not for everyone, but if you have something to share, I think you should try writing (that includes you too, Ben). I like this introduction to blogging from The Minimalists, posted about a month ago. It gives some basic general steps to getting started.  I get lots of comments from people who were glad they found Lympho Bob (and I love reading those comments), and it kind of lets me know that people are hungry for information and stories about Follicular Lymphoma. So if you are moved, pick a platform and a blog name and start writing.

Thanks again for the comment, Ben.

Saturday, December 12, 2015

ASH: Early CAR-T results for Follicular Lymphoma

Before I get to the cancer stuff, a couple of personal items:

First, I had my annual physical exam a couple of weeks ago. This wasn't an oncologist appointment, just my regular doctor, and she was pleased overall, especially with the 20 or so pounds I have lost since the summer. Everything looked good. I got my blood test results yesterday, and everything looks fine there (other than a little blood cancer, of course). My cholesterol is still low, and my vitamin D is high. My B12 is "on the lower end of normal," so I'm going to start a supplement. But otherwise, I think I have retaned my title as the healthiest cancer patient in town.

Second, today is my dog's birthday. She's nine years old.

She's a standard schnauzer, but unlike George, she's useless when it comes to sniffing cancer. But we love her anyway.


Now, on to the Follicular Lymphoma stuff.

The pharmaceutical company Novartis announced at the ASH conference that they are seeing good results with their treatment CTL019, a Chimeric Antigen Receptor T cell therapy, or CAR-T therapy.

CAR-T therapies are one of those treatments that are getting lots of cancer people excited these days. They seem to be working on lots of different types of cancer, liquid and solid, but seem especially suited to blood cancers like Follicular Lymphoma.

CAR-T is really cool. It's a type of immunotherapy, so it uses the body's own immune system to fight the cancer. Usually, cancer works because the body can't recognize that it doesn't belong there, so the usual immune system defenses (like T cells) just look the other way when they encounter a cancer cell.

CAR-T therapy makes sure that doesn't happen. T cells are removed from the body and given a reprogramming so they recognize the cancer cell as something to be destroyed. In the case of CTL019, the T cells recognize CD19, a protein on the surface of the cancerous cells (kind of like Rituxan recognizes CD20).  Once it recognizes the CD19 and hooks on to the cancer cell, it beats the crap out of it. says the CAR-T cells act like the antibodies that are naturally present in our blood, and expand to become a "living drug." They are effective as long as they stay in the blood and keep doing their job (which might be the tricky part). You can read more about CAR-T therapies for lymphomas at

The Novartis folks are working on a phase II clinical trial involving 15 patients with DLBCL and 11 with Follicular Lymphoma. All of the patients have advanced disease and "have not responded to standard treatment."

The Overall Response Rate for CTL019 was 47% for DLBCL patients, and 73% for the Follicular Lymphoma patients, which is pretty good. Apparently, they plan to apply for FDA approval in 2017; I assume they will applying for accelerated approval, since they are only on a phase II trial at the moment and it seems a little early in that trial, and even that might only be for DLBCL. The FDA gave CTY019 a "break through" designation for ALL last year.

One problem with all of this -- we're talking about a personalized treatment, so each batch will need to be made specially for each individual patient. Only your own T cells can fight your cancer. So it will be expensive, at least at first -- about $450,000 per treatment. (Yikes.) That price will come down eventually, but it's hard to say when, and how much.

But it's a really promising concept. We'll keep an eye out for future news about it.

Monday, December 7, 2015

Dr. Cheson's ASH preview

Well, the ASH conference is almost over now -- it finishes up tomorrow. But there is still lots to talk about from the conference.

It might seem like it's too late at this point, but here is an ASH preview from Lymphoma Rock Star Dr. Bruce Cheson from Georgetown University.

Dr. Cheson is always entertaining, and this video is no exception -- watch until the end for his surprise guest.

The video is a general preview of things that he is looking forward to from the conference, so he talk about more than just Follicular Lymphoma. But he does mention FL, specifically some of the studies that looked at Ibrutinib in various combinations for FL. (I think CLL is, once again, generating most of the excitement this year, but that's OK. We'll take what we can get.)

We'll see some press releases soon from university hospitals and pharmaceutical companies bragging about their ASH results. I'll pass anything along that looks interesting.

Enjoy Dr. Cheson's video.


OK, I had saved the link to Dr. Cheson's video, and now I'm having trouble accessing that link, so I don't know if the one above will work for everybody. But if you do a quick Google search for "Bruce Cheson ASH," you should find it (it's from Medscape). If you still have trouble accessing the video, or if you are looking for the text for translation purposes, Medscape was good enough to provide a transcript, which I am pasting below:

Hey, there. This is Bruce Cheson from Georgetown University Hospital, speaking to you for Medscape Hematology. It's that time of the year again: the American Society of Hematology (ASH) Annual Meeting preview for 2015.
I guess the people at ASH feel obliged to give us a few chemotherapy studies. There will be the third iteration of RCHOP-14 vs RCHOP-21 in diffuse large B-cell lymphoma. Will it be any better this time around?
As you know, there are two basic types of diffuse large B-cell lymphoma. There is the ABC, or activated B-cell type, and the germinal center type. The activated B-cell type traditionally does not do as well with standard therapy. However, certain drugs are preferentially active in this subtype, such as ibrutinib, lenalidomide, and bortezomib. At ASH, we're going to see the first results in large cell lymphoma of RCHOP with or without bortezomib in this population. Will it improve outcomes? I will not spoil the suspense.
We're also going to see results of bortezomib as either consolidation or maintenance following aggressive chemotherapy for untreated mantle cell lymphoma. There are interesting data there as well.
But what everybody wants to hear about are the novel targeted drugs. They're not even so novel anymore; there are so many of them out there. They want to hear about the non-chemotherapy approach for patients with lymphoma and chronic lymphocytic leukemia (CLL). There will be some single-agent data, including ibrutinib vs chlorambucil—the RESONATE-2 trial.
They're always trying to beat up chlorambucil. It's like the sick puppy out there that always gets drugs approved because everything is better than chlorambucil. We'll see in this trial with untreated CLL patients that the results are extremely impressive.
We'll see the results of ibrutinib in relapsed refractory follicular lymphoma. There was a previous abstract that showed a response rate of 28%, but there may be implications of a dose-response effect. Stay tuned for that one. We'll see the results of ibrutinib vs temsirolimus in mantle cell lymphoma, and we will see the results of venetoclax, or ABT-199, in CLL and non-Hodgkin lymphoma.
And now, we're into the second- and third-generation drugs. We're going to see some very exciting data on ACP-196, the new BTK inhibitor, in patients with relapsed refractory CLL. We will also see the idelalisib frontline data in chronic lymphocytic leukemia. There are lots of interesting single agents, but that's not where the action is, my friends.
The action is in combinations. We will see ibrutinib and rituximab in untreated follicular lymphoma. We're going to see a regimen that we developed in Alliance with R-squared: rituximab plus lenalidomide plus ibrutinib in untreated follicular lymphoma. We'll see various agents in combination with bendamustine, rituximab, bendamustine and rituximab, and we will also see venetoclax and the second-generation anti-CD20 antibody obinutuzumab. Promising data.
Speaking of obinutuzumab, it was approved for CLL on the basis of the CLL11 trial, in which it was rituximab/chlorambucil vs obinutuzumab/chlorambucil vs chlorambucil. Both combination arms were better than chlorambucil, but the obinutuzumab arm appeared to be superior to the rituximab arm. Okay, that's nice, but why don't we use a regimen in a study that's actually used to treat patients in this country? Well, we'll see preliminary data from the GREEN trial, in which there will be, as one of the arms, bendamustine and obinutuzumab. Let's see what happens with that study.
The excitement continues to mount for another class of drugs: the checkpoint inhibitors. There are lots of these in clinical trials. We saw at the last ASH meeting some astounding data with nivolumab in relapsed/refractory Hodgkin lymphoma and with pembrolizumab in a similar population. We will see at this meeting an update of those data. Do they really hold up over time? Let's hope so.
Again, combinations are where it's at. There will be a presentation on brentuximab vedotin (Adcetris®), the anti-CD30 antibody drug conjugate, plus a checkpoint inhibitor in relapsed/refractory Hodgkin's lymphoma. Those data will be of particular interest to me because I'm getting ready to activate a study of brentuximab vedotin plus nivolumab in patients with untreated Hodgkin disease. We'll also see data on checkpoint inhibitors in the treatment of patients with that really awful condition, Richter transformation.
I hope to see you in Orlando. Perhaps you'll also see this friend of mine. Excuse me while I move this camera. There he is. He's vacationing for the winter there, so Mr Mick and I will be running into you down there. Have a good ASH meeting, for those of you who go. For those of you who don't, we'll have a wrap-up session with Medscape Hematology afterwards.
Thank you very much. See you there. Bruce Cheson, signing off.

Monday, November 30, 2015

ASH: Life Expectancy for Follicular Lymphoma

Another review of an abstract from ASH.

This one is for a session called "Life Expectancy in Follicular Lymphoma Is Mainly Determined By Response to First Line Treatment: A Long-Term Survey of 597 Patients."It looks at 597 FL patients from two centers in Italy, and when the title says "long-term," it means just that: the patients were treated between 1976 and 2012.

Let me give an important reminder before we go any further: the world of Follicular Lymphoma research was very, very different in 1976. How different? Well, Rituxan was approved in 1997 and is made from mice. Some treatments approved in 1976 were made from brontosauruses.

Seriously, though, things were very different in the "Pre-Rituxan Era," and it's important to keep that in mind. As my old pal Dr. C told me a long time ago, anything you read online about Follicular Lymphoma is already out of date. And any study that looks at patients from 1976 to 2012 isn't taking into account any of the awesome new stuff that is in the development pipeline right now. So anything good that you hear, expect it to be even better. And anything bad that you hear, assume they are working on making that better, too.

Now, on to the research:

As the title says, in looking at these nearly 600 patients, the researchers found that one big factor in Overall Survival was how well patients responded to their first treatment. Patients who were fully refractory (that is, they didn't respond at all to their first treatment) had a median Overall Survival of just 2.7 years. Those with early progressive disease (that is, they responded to treatment at first, but the disease came back soon after) had a slightly better Overall Survival of 5 years.

For those who responded well to their first treatment, the median Overall Survival is 32.6 years. That's pretty dang good.

A couple of comments about those low numbers, in case anyone is in a panic:
First, remember that Overall Survival measures survival from any cause, not just FL. That includes heart attacks, snake bites, and being crushed by dinosaurs when trying to get cell samples.
Second, remember too that it's a MEDIAN Overall Survival. that means half of the patients in that sample had an OS of less than 2.7 (or 5) years, but half had an OS of MORE than that number. It could have been 2.8 years, or it could have been 28 years.
Remember that statistics like this don't predict what will happen to any individual. They are most useful in figuring out trends and deciding how to deal with those trends. In this case, the researchers think that these numbers mean researchers need to do a better job of figuring out which patients will be refractory to treatment and coming up with strategies to deal with that immediately.
(And I think it's possible that they already have. Some recent research seems to show that people who relapse very early on might need to be considered a different sub-group of FL.)

Now, for that group that responded well to their first treatment and has a median Overall Survival of 32 years: the same warnings apply for them. Median means half are on each side of that number, and there are other factors in the research that show how all of that plays out. For example, patients over 60 have a much lower OS than those younger than 60. And patients who had Rituxan have a higher OS than those who don't. And patients with bone marrow involvement have a lower OS than those without it.

But even those numbers don't say anything about individual patients.

Here's my take on it all: Like I said at the beginning of this post, there is a lot that has happened since 1976 that we should be happy about. The high OS numbers for some patients show us that. I remember looking at Wikipedia's Follicular Lymphoma entry when I was diagnosed in 2008 and seeing the median OS at 8-10 years. We're at 3 or 4 times that now, according to this research. (That 2008 number was probably a lot lower than it should have been, but still -- things are improving.)

And even those low numbers, while scary, need to be taken the right way. We are learning more and more about how FL works, on a genetic scale. In other words, researchers are identifying the tiniest bits of our cells that are out of whack and causing our disease to behave the way it does. Every day we get a little closer to being to able to pinpoint which treatments are likely to work with which out-of-whack cell pieces. And in the meantime, we have more treatments to try, more arrows in our quiver (thanks again, Dr. C) if that first treatment does fail. A heck of a lot more than we had in 1976, for sure. (Heck -- Rituxan was still 20 years away back then.). So all is not lost.

Lots of hope here, folks.

Thursday, November 26, 2015

Happy Thanksgiving

Once again, we come to Thanksgiving Day, the day in our country when we try to take a little time to think about the things we are grateful for. Sometimes that's hard to do, for lots of reasons, but I like to think that all of us have at least one thing, maybe even a small thing, to be thankful for.

It's easy for Thanksgiving Day to be about something other than giving thanks. If you are not from the U.S., you may not know all of the traditions. There is often a lot of food -- good food, probably too much food, for some of us. There is football. There are jokes about relatives, and avoiding sensitive topics of conversation. There is a lot of good stuff to be thankful for, and sometimes we forget to be thankful for things.

I have been trying to give some thought to what I should be thankful for. I've been so busy lately that having an annual Thanksgiving blog post is a nice way to make sure I take some time to think about this. I'm a lucky man, which might be a funny thing for someone with incurable cancer to say. But it's true. I have a lot to be grateful about.

To be honest, I couldn't remember what I wrote about last year. I wasn't sure if I even got around to writing. So I looked back, and sure enough, I had written a Thanksgiving post. It was about my family, which I was truly grateful for -- and still am. I think I managed to thank everyone in my family, near and far. But there was a very big hole in that list.


Earlier this month, I saw that there was an event nearby called "Dear World." For the event, people throughout the day are asked to write something on their skin -- their arms, chest, face, wherever -- something that sums up a message they want to send to the world. Then they are photographed against a a black background. Later that night, there is an assembly where all of the photos are shown on a screen, and people realize that there is a lot that makes them alike, despite their differences.

Unfortunately, I was not able to make it to the event. But it made me think a lot about what I would write on my skin, what kind of message I would want to share with the world. I have a lot of skin, so I could probably write a full 750 word blog post if I really wanted to. But I decided I would keep it simple, up one arm and across the other, in thick black marker:

See the Humor.

I think one of the things that has gotten me through cancer has been my ability to see the humor in bad things. It doesn't mean I ignore them or put them off -- you can't just pretend a cancer diagnosis doesn't exist, at least not for very long. But what you can do is not let it overwhelm you. I wrote, very early on, that I refused to let cancer take away my sense of humor, and making fun of cancer was my way of spitting in its eye and taking away its power.

I think I got that way of looking at the world from  my mom.


I've written about my mom here before, but I'm pretty sure I've never revealed that she died about a year and a half ago. She, too, had cancer, which I know I did reveal. (It was ovarian, because I know you'll want to know. Cancer patients are nosy that way.)  We used to laugh about cancer together, which is one thing I would have preferred that we did not share.

I remember a few days after I was diagnosed, my parents came to visit. We had asked them to come for the weekend, mostly so they could keep an eye on the kids, We had told the kids about my diagnosis on Friday afternoon, and we thought mom and dad might pick up on their anxieties that they wouldn't want to share with us. Mom and dad were in the basement with the kids, so I set the table for dinner. Mom came up a few minutes before dinner was ready, and saw that I had already set the table. "Oh," she said, "I was going to help with that." I told her, "Yeah, the work is done. Nice. Make the guy with cancer do all the f--ing work." She laughed, and then stopped herself. "I can't believe we're laughing at cancer." I made her promise she wouldn't stop.

And she didn't. A few years later, we were at a baseball game, in line to buy ice cream. She was dealing with her own diagnosis. I told her she should tell the ice cream man she had cancer, and maybe she'd get free sprinkles. She laughed and said she could never do that. But when he was dishing up her ice cream, she said very softly, "I have cancer." I don't know if the young man didn't hear her, or didn't know quite how to respond, but she didn't get free sprinkles. She wasn't happy. But we had fun.

I've told those stories before, and I have lots more, but those are two of my favorites.


So I got that perspective on the world from her.

Even people without cancer can have troubles.

The world can be a pretty absurd place. I get reminders of that every day.

A reasonable response would be to curl up in a ball and just not deal with any of it.

A better response, to me, is to see the humor in it all and deal with what comes.

That's what I do. I get it from my mom.

And that's what I'm thankful for this year.

Sunday, November 22, 2015

ASH: Watching and Waiting

Another ASH Abstract: "Watchful Waiting As Initial Management of Advanced-Stage Follicular Lymphoma in the Rituximab Era: Analysis of the National Cancer Data Base."

If you've been reading for a while, you know that I was diagnosed with Follicular Lymphoma in January 2008, and had Rituxan in January 2010, which meant I had two years (exactly two, to the day) of watching and waiting, so I'm always fascinated by the topic.

I also know it's a controversial one, with lots of evidence on both sides of the controversy: with advanced FL with no symptoms, is it better to watch and wait, or to treat right away (with Rituxan being the typical alternative to W & W). There is new research on this controversy, it seems, once or twice a year, but nothing that really says one is better than the other. 

This study from ASH is a little different. It doesn't try to solve the controversy. Instead, it tries to show just how common watching and waiting really is by looking at trends from the National Cancer Data Base, which includes information for more than 70% of cancer incidents in the United States from 2004-2012. They looked at stage 3 or 4 Follicular Lymphoma that did not have B symptoms, and that held off treatment for at least 100 days from diagnosis.

Researchers found 18,783 instances of FL advanced stage (3 or 4) patients, and about 31% could be called Watch-and-Waiters. The study lays out a bunch of statistics that show how watching and waiting is used, but a few of them are particularly interesting (to me, anyway):

Watching and Waiting was much more common in New England and the West Coast (39%) than other parts of the country (the South, for example, was just 22%). They don't offer an explanation for this, but as a New Englander, I thought it was pretty interesting. The researchers don't speculate why, but my guess is that certain medical schools/residencies favor that approach, and their graduates stay fairly close by. The study also shows that research hospitals use watching and waiting more often than community hospitals, which might back up my guess.

Overall Survival was a little better for watch-and-waiters than those who were treated right away (76.9% vs 74.3%), which they expected. This doesn't mean that watching and waiting  increases your survival chances; it means people with slower-growing FL are more likely to still be watching and waiting after 100 days. The statistical difference goes away when some other factors are included.

Finally, there was no association between watching and waiting and things like median income, type of health insurance, or distance from treatment facility. This is important -- watching and waiting isn't just an excuse for doing nothing because it's just easier and cheaper to do nothing. Instead, it's a legitimate treatment strategy, done deliberately. (Though the researchers do think payment policies in oncology practices might be having an effect on how often it is used.)

So overall, the presentation gives a bigger picture of watching and waiting, even if it doesn't tell us anything new about the controversy over whether watching and waiting is the best approach. As the researchers point out, the National Cancer Data Base doesn't have the kind of detailed information about individual patients that could tell us more about watching and waiting, and (to my delight) they admit that clinical trials about watching and waiting probably aren't going to show any kind of Overall Survival benefit to immediate treatment over watching and waiting. So what we have here is probably as good as it's going to get when it comes to our knowledge about it.

I'd say I still feel the same about my own choice from long ago. I'm glad I chose watching and waiting, and I think others should feel good about the (sometimes difficult) choice as well. 

Tuesday, November 17, 2015

ASH: Ibrutinib and Follicular Lymphoma

Here we go: Time to get into the abstracts for the ASH conference, where researchers will present the latest and greatest on all things related to blood diseases, including Follicular Lymphoma. It looks like CLL is going to get a lot of coverage again this year, just based on the number of presentation listed. Follicular lymphoma doesn't have nearly as many, but there is some interesting stuff in there, in my opinion.

There are several sessions that focus on Ibrutinib, the BTK (Bruton's Tyrosine Kinase) inhibitor. BTK is an enzyme that plays a role in B-cell development. By cutting off that enzyme, Ibrutinib stops B cells from developing. FL is, of course, a B cell lymphoma. 

I saw three interesting Ibrutinib/Follicular Lymphoma abstracts.

The first is "Ibrutinib Plus Rituximab in Treatment-Naive Patients with Follicular Lymphoma: Results from a Multicenter, Phase 2 Study." The title is pretty straightforward: in a phase 2 clinical trial, patients who had not received any treatment were given Ibrutinib and Rituxan (Rituxan once a week for four weeks, and Ibrutinib every day -- it's a pill, taken by mouth, for as long as it was tolerated or effective. The Overall Response rate was 82%: 55% had a Partial Response and 27% had a Complete Response. (The remaining 18% had stable disease.) Side effects seemed mostly tolerable, and in line with the side effects for Rituxan and other Ibrutinib combinations. Good news for this combination.

A second study,  "Long-Term Follow-up and Analysis of Dose Groups with Ibrutinib in Relapsed Follicular Lymphoma," tried to determine the best dose for straight Ibrutinib for patients who had relapsed or refractory Follicular Lymphoma (that is, their last treatment stopped working, or didn't work in the first place). This was a small study -- only 16 patients. 8 were given a low dose, and 8 were given a high dose, and patients kept taking it until it stopped working or side effects got too bad. The high dose group did better -- all 8 had a response, and it lasted 12 months (median). The lose dose group lasted 4 months (median), and only 2 had a response. Progression Free Survival was also considerably higher for the high dose group (24 months vs 9 months). The study suggests that higher doses might be better (measured by mg per kg of body weight) than the current standard of 560mg (whatever the patient's body weight) currently being used.

Finally,  "Phase I Study of Rituximab, Lenalidomide, and Ibrutinib in Previously Untreated Follicular Lymphoma (Alliance 051103)" looks at R-Squared (Rituxan + Revlimid/Lenalidomide) plus Ibrutinib. As the abstract points out, R-squared seems to be working on FL, so there are several attempts to make that combination even better by adding other agents -- in this case, Ibrutinib. Results were good -- 91% Overall Response, close to the 93% Response for R-squared. However, there was a "significant incidence of rash," which the researchers say is common with Ibrutinib. The Conclusion mentions the Response Rate and the high rash incidence, but doesn't say whether that justifies moving on to a phase 2 trial (it might also be too early in the study to decide that).

So there are your three interesting Ibrutinib and Follicular Lymphoma sessions at ASH. 

It's important to point out that Ibrutinib is not yet FDA-approved for Follicular Lymphoma (though it is for some other blood cancers), but there seem to be a whole bunch of trials going on that involve Ibrutinib, at varying levels of success. It seems likely that it will get FDA approval, in some form, at some point. But these abstracts show that it still seems like it might be a while before we see that approval, since it's pretty early still. It also seems more likely that we'll see success by combining Ibrutinib with something else, rather than seeing it being used on its own.

Still, some good stuff here.

Tuesday, November 10, 2015

ASH Conference!

As usual, Christmas has come early this year:

The abstracts for this year's ASH conference are out. That's the American Society of Hematology, and it's perhaps the largest gathering of blood specialists in the country.

I took a quick look at the abstracts for Follicular Lymphoma, and it looks like there's some good stuff there.

The ASH conference usually involves presenting very early results from trials, or even pre-trial work. In other words, what gets presented is usually a few years away from showing up in the oncologist's office, if it shows up at all. But it does give a good sense of what's being worked on, and how likely we are to see some of those new treatments.

The conference happens December 5-8 in Orlando, Florida (a lovely place to be in December), and I would expect to see some Preview articles or videos just before the conference. These are great, because they give us a sense of what the experts are excited about. It would be nice to see some Follicular Lymphoma research being highlighted.

My plan, as usual, is to highlight and comment on the abstracts that seem exciting to me. I'll do my best to get to them soon.

Tuesday, November 3, 2015

How I Move On

I got this comment this morning on my last post, and I started to respond to it in the Comments section, but I decided to post it here because I was afraid it might get lost, and it was getting too long. Anonymous, I hope you don't mind my sharing the comment here in a more visible place.

Anonymous said...
Hi Bob,
I was diagnosed with Marginal Zone NHL a little over 2 years ago and had RCHOP off the bat, because I was really sick (in ICU for 2 weeks, several blood transfusions etc) followed by 2 yrs of Rituxin maintenance. I'm sorry if this is off topic, but I was wondering how the news of Senator Fred Thompson's death hit you. He was diagnosed with Marginal Zone Lymphoma 10 years ago, had radiation, then eventually was treated with Rituxin and went into remission for several years. I don't know about you, but every time we lose a public figure to NHL, specifically Indolent NHL, it brings me right back. Thank God for blogs like yours that focus on all the new treatments etc. However, situations such as Thompson's death make me realize that sometimes, we do run out of options...

November 3, 2015 at 11:26 AM

Anonymous, thanks for writing, and I'm sorry to hear that you had such a tough time when you were diagnosed and treated. It sounds like you're doing better now (I hope so, anyway).

Here's what's going through my head.

I've been thinking about Fred Thompson's death since I read about it a couple of days ago. He was, really, the first big celebrity that I mentioned in the blog -- a few weeks after I was diagnosed, he dropped out of the race for the United States presidency. Yes, a television personality was running for the Republican nomination in 2008. So much has changed since then............

I would, of course, go on to write about other celebrities with Lymphoma, in my "Nodes of Gold" series. Actor Mr. T,  Chicago Cubs pitcher Jon Lester, comedian Artie Shaw, Black Sabbath guitarist Tony Iommi, and many others. The idea was to show that even famous people weren't so different from us. They were still vulnerable.

But the secret to Nodes of Gold wasn't just in highlighting famous people. It was in highlighting famous people who were still alive. There are plenty of famous people who had lymphoma and didn't survive. Aviator Charles Lindbergh. Ramones lead singer Joey Ramone. King Hussein of Jordan. Former First Lady Jackie Kennedy Onassis. Lots more.

But I don't talk much about death in Lympho Bob. I don't think it's what people want to read about. It's not what I want to read about, and as I've said before, even if nobody else read this blog, I'd still write it, just for myself. Because reading and writing about where we are with Follicular Lymphoma, and where we might be soon, gives me hope. The blog is a hopeful space for me. It's hard to write about cancer. If I had to write about all the bad stuff, I don't think I could do it so much.

So while the blog is a hopeful space, that doesn't mean I don't think about death and dying, and as you say, Anonymous, we get reminders of that in the news every now and then. We get reminders in real life, too -- kind of an unfortunate side effect of still being in the online NHL support group. Sometimes we lose members. Sometimes those are people who we had gotten to know well. That hurts, not only because we feel for their families and friends, but also because it reminds us of our own mortality.

I've gotten good at pushing some of that sad stuff out of my head. I think the blog helps. I can focus on good things here, and writing about them helps me focus on them even more than just reading about them would. That doesn't mean I push them completely away, or that I could, or that I'd want to. I think about lymphoma every single day. I'm almost always search for and reading about stuff for the blog. And I check in with the online support group every morning -- it's just part of the routine now. Awake before the family, make a cup of tea, read email, check the news, read about lymphoma. 

But while I think about it, I don't dwell on it. That's a key difference.

And being almost 8 years out since diagnosis has made that easier. Not easy, but easier. Being almost 6 years since treatment has helped, too. And knowing as much as I know about Follicular Lymphoma has also helped. It wasn't always so easy to push things out. It comes with time. 

And, unfortunately, with practice.

I wish I could say that I gathered strength or inspiration when I read about people dying from lymphoma, whether they are famous or not. I wish I could say I read about their struggles, and how brave they were, and it inspired me to fight. That's not really true. It doesn't make me feel stronger. If anything, it makes me feel sadder, for a few days.

But, to be honest, at some point, I feel like I have to move on, as hard as it might be. At some point, it isn't about the person who died anymore, it's about me. I have to look at my own life, what I hope to do, what I hope to be, and then do and be that thing. It's not always easy, and sometimes it's not so much about moving on, but really just pretending that I'm moving on and going through the motions. But it's what I feel like I have to do.

I've gotten good at using my brain and not my heart when it comes to something like death. I can remind myself that we don't know much about Fred Thompson's condition, if he had other health problems that might have made him more vulnerable to the lymphoma. We don't know if he had some particular genetic sub-type that was less apt to respond to certain treatments or that affects only a certain percentage of patients (to be honest. I know very little about Marginal Zone, and if it even has sub-types that are susceptible to becoming more aggressive). I can remind myself about all of the great treatments that are already available, and the even better ones that are on the way. 

That fear -- it never goes away. It never gets easy. But it does get easier. 

I hope you remember to hope, and I hope you find some peace.

Thursday, October 29, 2015

Immunotherapy Explained's parent group, Patients Against Lymphoma, recently posted a video on their Facebook page (click here if you want to Like and join) that does a very good job of explaining Immunotherapy, an important approach to fighting cancer.

The video was produced by the Dana-Farber Cancer Institute in Boston, and shows how the specific immunotherapy known as PD-1 pathway inhibitors work. I'd explain it here, but it's a short, clear, and kind of fun video, so you can watch it yourself. Click the "video" link above, or watch here:

Good stuff.

PD-1 inhibitors are showing some success with a bunch of different cancers, both solid and liquid, including Follicular Lymphoma.  Certainly worth keeping an eye on.

Friday, October 23, 2015

Lymphoma Movies

Lymphoma News Today posted a fun article yesterday called "13 Movies about Lymphoma."

OK, so watching a movie that features your own incurable disease might not be everyone's idea of "fun." But maybe, if you're watching as a cancer nerd, you can sneer at their misinformation and point out their bad science and medical mistakes. That's always fun. For me, anyway.

Seriously, though, watching a movie about someone with cancer was kind of a major emotional step for me. When I was able to do it, it was because I had enough distance from my disease to be able to see someone else having cancer, and not think about myself. It was a big step for me. (I've never watched Breaking Bad, which some people think is the best TV show ever made, because it premiered about 2 weeks after I was diagnosed, and featured a teacher with terminal cancer who started making meth so his kids could be taken care of. All a little too close to home at that point.)

One really, really important thing to remember, though -- movies have a way of playing with the truth. A filmmaker's job is to tell a story, not educate you in medicine. So if you do watch one of these movies, keep that in mind. Not only does a character's journey not have to be your journey, but it might not be anyone's journey, because it was easier to tell the story by making up details about the disease.

You can go to the link above to see videos of scenes or trailers for most of the movies, but I'll give you my own preview to help you decide:

1) Sweet November (2011). Keanu Reeves and Charlize Theron. One of them gets terminal NHL. It's supposed to be a romantic drama, but I think it would come off as funny, because I can't help thinking of Bill and Ted's Excellent Adventure whenever I see Keanu Reeves, which is really too bad.

2) A Few Things about Cancer (2014). Nonfiction film, a story about a real young man with Burkitt's Lymphoma. This one might be hard to watch, but I really admire him for being willing to have his story told.

3) Athlete (2010). Another real-life story. This one features a lymphoma survivor, one of four people profiled who compete in marathons and triathlons. This one will inspire you.

4) October Sky (1999). Awesome movie about a teenager in a coal mining town who dreams of becoming a rocket scientist. Lymphoma does play a role, but you will feel so good after seeing this movie that you won't care.

5) My Lymphoma Year (2011). Sorry, don't know anything about it and can't find much about it.

6) The Weather Man (2005). Nicholas Cage. So probably as funny as anything Keanu Reeves is in.

7) Erin Brockovich (2000). Julia Roberts as a real-life crusader against cancer-causing pollution by a big business. She won an Oscar, and she wasn't even the best actor in the movie. (That would be Albert Finney.)

8) Five Star Day (2010). A guy's horoscope says he will have a great day, and it turns out to be horrible. He tracks down other people born on the same day to see if their horoscope came true. You can probably guess where lymphoma fits into this.

9) *batteries not included (1987). Kind of like "The Shoemaker and the Elf," but with small flying robots that are alive. I saw this when it first came out. Hume Cronyn and Jessica Tandy are an adorable old couple.

10) The Substance of Fire (1996). Family drama centered around grief. Timothy Hutton is featured.

11) Bang the Drum Slowly (1973). Basball/cancer movie, with a very young Robert deNiro. You'll cry, especially if you're Cubs fan, because you're already very emotional right now.

12) Infinity (1996). Biography of Richard Feynman, who won the Nobel Prize for Physics. Starringa nd directed by Matthew Broderick.

13) They Came to Play (2008). Another documentary, this one about an international piano competition for talented amateurs. Another inspiring film, too.

One thing I've noticed: there are a lot of lymphoma movies that feature actors who have won or were nominated Oscars (even Nicholas Cage!). Take that as an endorsement.

So if you feel emotionally prepared, try a lymphoma movie this weekend. (My recommendation: October Sky.)

I, personally, will be trying to catch up on Doctor Who.

Tuesday, October 20, 2015

Targeted Approaches to Follicular Lymphoma

Cancer Network  published a review article from Dr. Chaitra Ujjani a few days ago called "Targeted Approaches to the Management of Follicular Lymphoma." I think it's as good a summary of where we are with FL treatments as you're going to find -- pretty up-to-the-minute stuff.

Dr. Ujjani attempts to describe the targeted approaches to Follicular Lymphoma that are out there, either as approved treatments or in various stages of clinical trials. "Targeted" basically means a treatment that doesn't try to kill off cancer cells the way traditional chemotherapy does, but instead uses our understanding of how cancer cells grow and survive to attack those processes. The "target" isn't the cancer cell, but the things that let the cell live, usually unique to that type of cell.

The article opens with a basic understanding of how Follicular Lymphoma has usually been treated with chemotherapy, and of how that understanding has changed what we know, and how we treat it.

The article then goes on to describe the different types of treatments, how they work, and how successful they have been so far. Before I get into some of those types of treatments, I want to share a table from the article that lists those treatments:

Targeted Approaches to the Management of Follicular Lymphoma - See more at:

That's a pretty nice list. Even if you don't understand any of what is on the list, it's pretty cool to see just how many treatments are out there in various stages of development. Even if half of them, even one quarter of them, were eventually approved, we'd have a bunch more options than we have now. That's just a chart full of hope right there.

As for the specific types of treatments, Dr. Ujjani gives a nice description of them:

Newer Anti-CD20 Monoclonal Antibodies: The granddaddy of targeted FL treatments is Rituxan, which has really changed FL patients' lives in amazing ways. Rituxan targets CD20, a protein on the surface of FL cells. As amazing as Rituxan is, it has its problems, and researchers are working on alternatives to Rituxan that can be even more successful with fewer side effects. These include Ofatumumab and Obinutuzumab, which have approved for CLL, but not yet for FL.
ofatumumab and obinutuzumab
ofatumumab and obinutuzumab

Monoclonal Antibodies to Alternative Targets: CD20 isn't the only protein on FL cells that can be targeted. Others include CD80 and CD22. But most promising seems to be antibodies that target CD19. There are a couple of treatments in development that target this protein.

RadioImmunoTherapy: I've written a lot about RIT, and how underused it is (for lots of reasons that seem to have more to do with how it is administered than how effective it might be). RIT involves putting a dash of radiation onto a monoclonal antibody, so the radiation can be delivered directly to the FL cells.

Antibody-Drug Conjugates: ADCs are sort of like RIT, in that they involve using something like a monoclonal antibody that can track down an FL cell, and attaching a small bit of a drug to it, so that the drug is delivered directly to the cancer cell. So instead of traditional chemo, which will kill any cell in its path, the ADCs make sure only targeted cells get the drug delivered to them. The article mentions four ADCs in development.

Tumor Microenvironment: These treatments don't focus on the cancer cells themselves, but on the stuff happening around the cell that is necessary for the cell to survive. An example of this is Lenalidomide, also known as Revlimid. Lenalidomide can affect cancer cells directly, but it can also mess with stromal cells in the bone marrow, which support the blood cells. So tumor microenvironment targets mess with things that support the cancer cells, and not necessarily the cells themselves.

Small-Molecule Kinase Inhibitors: Finally, there are the various Kinase Inhibitors, like Idelalisib. These treatments inhibit certain enzymes from doing their job. These enzymes are usually messed up, and allow cells to grow much longer than they are supposed to. By inhibiting them, they keep cancer cells from growing too large and too long. These treatments are a big step beyond chemo as well because they show that a cell cam be stopped by shutting down important parts of the cell, rather than killing the cell outright.


You can learn more about the different types of treatments by reading the article.

One important thing to remember -- as inspiring as it is to see all of these treatments in one place, they are almost all still in development, working their way through clinical trials. Which makes me think of something I read once from Karl Schwartz, President of Patients Against Lymphoma/ all of these treatments are useless if patients don't volunteer for clinical trials themselves. Great treatments don't get approved if they haven't been shown to work, and the only way to show that is to test the treatments on patients. Something to think about if you ever need treatment (though we also hope that doesn't happen for a long time, or ever).

In the meantime, we have much to be hopeful about.

Wednesday, October 14, 2015

Follicular Lymphoma Stories

It's been kind of a quiet week in Follicular Lymphoma Land. Not a whole lot of research popping up (a few things, but they're either so dense that I'm still trying to understand them, or so narrow, and effect so few patients, that I'm not sure it's worth writing about).

But I haven't written anything in over a week, and I'm getting a little anxious. I've been snooping around the internet, trying to find something interesting to write about.

So I've gathered some stories for you.

I know, for me, hearing someone else's stories is always a comfort, especially when they are stories of hope and success. September was Lymphoma Awareness Month, so it was a good excuse for lots of folks to tell their stories. And then there are the sites that features patient stories year-round.

So maybe click on a few and get a little hope?

ChicagoNow has an interview with a Follicular Lymphoma patient in an article called "Non-Hodgkins Lymphoma: An Interview with a Fighter." It's a familiar story -- a shocking diagnosis and a willingness to learn about her disease -- biut it's good to know we're not alone in this, and that it's best not to be.

Here's another: an interview with a patient and her oncologist for Lymphoma Awareness Month, from WOCA radio in Florida.  The radio interviewers don't know much about FL, which is fine -- they ask some good questions, and get some good information -- and pass it on to their listeners. I always enjoy hearing an oncologist get excited about helping a patient, and sharing his hope.

Those are pretty recent stories, but there are others out there, to.

The Lymphoma Research Foundation has an ongoing section of their website called "Stories of Hope," with a separate section for stories from patients with Follicular Lymphoma (including a story from Lymphoma Rock Star Betsy DeParry).

And has a whole bunch of stories from patients about their experiences with being diagnosed, with specific treatments, and with the psychological effects of the disease. And they also have a unique section with poetry and art -- a different type of story-telling.

My kids used to love to hear stories from me, and they still do, especially stories about my life and the nutty people I've known (and there are lots -- I seem to attract them, which is a wonderful thing). Stories like that help us connect, and sometimes remind us that what we are feeling isn't as unusual as we might think.

I hope you enjoy some of these stories, and feel some connection.

And I'll keep searching the web for interesting things to write about.

Tuesday, October 6, 2015

Increasing Failure Free Survival in Follicular Lymphoma

I've been sitting on this for a couple of weeks now, but:
A presentation at the annual meeting of the Society of Hematological Oncology (SOHO) last month highlighted that treatments for Follicular Lymphoma seem to be improving Failure Free Survival rates. OncLive has a story.

OK, a couple of things before we move on. First, this is the first time I had heard of SOHO. I'm not an oncologist, but goodness knows I read enough about blood cancers, so I'm a little surprised I hadn't heard of SOHO before. Turns out the group was founded in 2012, so I feel a little better about that.

Second, I am less familiar with the term "Failure Free Survival" (FFS) than I am with other measurements for cancer treatments. I'm used to reading about Progression-Free Survival" (PFS), which I think is a more common measurement. Are FFS and PFS the same thing? I'm really not sure. They seem to be measuring the same general thing -- how long after treatment until the disease returns, but there are also some very subtle differences between similar ways of measuring how effective a treatment is, and I'm not prepared to say they are the same thing. I'm happy to hear from anyone who can explain the difference, if there is any.

So back to the article, and the SOHO presentation, which was delivered by Dr. Nathan Fowler from MD Anderson:
Despite an increase in Overall Survival for Follicular Lymphoma, there hasn't been a big change in Failure Free Survival. In other words, it's still about 5 years before the disease comes back, for most treatments.

According to Dr. Fowler, that might be changing, with newer treatments that target pathways instead of targeting the cells themselves. As we are learning more and more, killing off FL cells seems to depend not just on killing the cells themselves, but in messing with the processes that allow them to grow and survive -- the different "pathways" that they rely on.

Dr. Fowler discusses a few newer treatments, and the increases in Progression Free Survival that seem to be coming about.

For example, Ibrutinib is a BTK inhibitor. [I was going to describe how all of these treatments work, which I've done in the past, but I'm going to send you to instead. You can find descriptions on their Treatments pages, especially the page on Agents that Target Disease Pathways. They will do a more in-depth job than I can here.]

As Dr. Fowler points out, trials involving Ibrutinib have shown that different doses seem to have an effect on PFS. A phase III trial is underway that will compare B-R and R-CHOP with and without Ibrutinib. And finally, a trial was recently completed that looked at Ibrutinib + Rituxan as an initial treatment for FL. The results might be ready for ASH in December.

Dr. Fowler also discusses Idelalisib, Obinutuzumab, and R-Squared (Rituxan + Revlimid/Lenalidomide), all examples of newer pathway treatments. He brings up some interesting points about these newer treatments, such as the fact that they have fewer side effects than traditional chemotherapy, but those side effects can themselves be pretty severe.

Another interesting thing has to do with the whole PFS/measurement issue: some of the trials for these pathway targets show relatively low response rates, but that is because, ironically, the treatment is working well. In other words, only 25% of the people in a trial show a shrinkage in tumors, but many of the rest didn't have a shrinkage, but they didn't have growth, either -- they had stability, and that's not a bad thing (but it's also not the thing that's being measured).

So all in all, it's a nice overview of some the research that's being done on newer treatments, and a nice commentary on some of the things that make these newer treatments so different from what we're used to.

Plus, it already has me excited about the ASH conference, even though that's two months away.....

Thursday, October 1, 2015

Important FL Gene Mutation Discovery

A couple of weeks ago, the journal Nature Medicine published an important article a couple of weeks ago called "The Histone Lysine Methyltransferase KMT2D Sustains a Gene Expression Program that Represses B Cell Lymphoma Development." Some of the researchers are from Sloan Kettering, and they have a nice explanation of the study on their blog, and I recommend you take a look. Or, if you're too lazy to click, I'll give my own summary here.

I think it's fair to say that mapping the human genome changed cancer research, and Follicular Lymphoma research has certainly benefited. As researchers understand genes, and how genes mutate and change, they understand how those changes mess up the way cells normally behave. And as we all know, messed up cells that misbehave means cancer.

The researchers in this study already know that a gene called KMT2D mutates in about half of Follicular Lymphoma patients (and some Diffuse Large B Cell Lymphoma patients, too). But they didn't really know what that mutation did. Usually, when a gene mutates, it leads to a specific action that causes cancer, or helps sustain it. Researchers have already identified a bunch of gene mutations and figured out how they make FL happen.

To figure out what KMT2D does, they relied on a mouse model -- basically a mouse with Follicular Lymphoma that is close to what a human would have. The researchers found a way to block the KMT2D -- this way they could work backwards and see what the KMT2D would have done had it been working.

They found something they didn't expect -- the KMT2D didn't control one particular cell function. Instead that gene controls hundreds of other genes, and they control cell functions.

No one is called this a "master gene" or anything like that, and figuring out how to control the mutation isn't necessarily going to lead to a cure. Still, one of the lead researchers did say, "This is the most important mutation in this incurable disease, and we figured out what it does." When this gene gets messed up, it keeps a whole lot of other things from happening.

So this is a major step in understanding Follicular Lymphoma. Maybe not the final step, but definitely a major step. And it will take some time for other researchers to figure out how to control it, and then to develop, test, and get approval for actual treatments. But it's a very promising start. (I love to read about FL experts getting excited about a discovery. It makes it all a little more real.)

Read the Sloan Kettering blog for more detail. It's worth the read.

Saturday, September 26, 2015

Folicular Lymphoma is Complex....

Recently, the annual Debates and Didactics in Hematology and Oncology conference was held in Sea Island, Georgia. it is sponsored by Emory University.

A couple of weeks ago, The ASCO Post reported on the conference, particularly the session from Dr. James Armitage of the University of Nebraska (he also serves as Editor-in-Chief for The ASCO Post).

One of the main points that Dr. Armitage made was that Follicular Lymphoma is a lot more complex than we used to think. The cells surrounding the lymphoma cells, according to Dr. Armitage, play a role in the Lymphoma's survival. This probably doesn't come as a surprise to any of us. If you've followed where FL treatments have been, and where they are heading, it's easy to see that, gradefor most of us, a single treatment from a single agent just isn't going to do the trick, at least not permanently. Researchers are learning more and more about what makes FL so complex, and trying combinations that will deal with the different parts of the disease that make it so complex.

So Dr. Armitage tries to review some of the different treatment options available. This isn't an article that's offering anything new. But that's OK by me. I like to stop every now and then and see a nice summary of where we are now. It helps understand where we might be going.

Dr. Armitage looks at some controversies that have been in the news in the last few years, like the whole Watch and Wait issue (which I vowed not to write about again unless there was something new to report).

He has nothing new to report.

(W & W is OK if the patient is asymptomatic or elderly, but observation has to be very careful -- no just forgetting about it. As if that was possible for most of us......)

He also looks at research on R-CHOP vs. R-CVP, but says R-CHOP vs. B-R is more important. Both are better options than R-CVP, though a German study found Bendamustine worked better than CHOP. However, a United States study found Bendamustine to be not as effective as the German study fund it to be. Still, though, both have their place, and both work well.

He also mentions R-Squared -- Rituxan + Revlimid (or Lenalidomide), which had great results in trials, though as more patients use it, it seems to be not quite as effective as we thought. But as we learn more, he thinks it could be as useful as R-CHOP and B-R.

So how to choose among these options? Dr. Armitage thinks a bunch of things need to be considered -- age, health, symptoms, comfort with certain side effects, etc.

But he seems very clear about one thing -- the goal of the treatment should be a Complete Response. He doesn't think it is valuable to treat just to make the patient feel better or push things off for a while. Complete Responses have a "huge survival advantage," according to the article. He also thinks relapses are very difficult on patients (I think he means emotionally difficult), so he aims for CR and uses Rituxan Maintenance, which may prolong Progression Free Survival (though not Overall Survival), giving patients more time between treatments.

That's an interesting perspective. And one that some other oncologists would probably disagree with. (I remember the Lymphoma specialist I saw soon after I was diagnosed told me, Put 12 Lymphoma specialists in a room, and they'll have 13 opinions.)

Which brings us back to the idea of how complex Follicular Lymphoma is.

The good news, as always, is that we have some options, and there are even more on the way.

Nice to remind ourselves about that.

Monday, September 21, 2015

My Oncologist Appointment

I had a four month check up with Dr. K, my oncologist, today.

Everything looks great.

This time, he did a blood test. He had skipped it last time because he says blood tests don't really show anything, so he does them every six months at the earliest. The blood test was fine -- no significant changes from December, the last time I had one.

He did a physical exam, poking around here and there, feeling for any nodes popping up. Again, no changes since the last time he felt me up.

Then he gave me a lecture about CT scans, and why I wouldn't be getting one -- NCCN guidelines have changed over time, and we used to do scans every 6 or 12 months, and now we know that frequent scans over a long time have a risk of causing a secondary cancer, etc. etc. I tried to interrupt him a few times to say I was OK with waiting a long time between scans, but I couldn't really stop him from talking.

The important thing is, my health is good.


After my first appointment with Dr. K, I wrote about how much I had missed Dr. R, my old oncologist. We had a great relationship. We could joke and tease, and talk about current research, and even his secretary would show us pictures of her grandkids. It seems a little strange to say, but going to the oncologist was actually fun.

It's pretty clear that things just aren't going to be that way with Dr. K. It's just not his personality. And it's only been two visits, but it seems like the whole office is the same way.

The word that kept coming to me was efficient.  The whole office is efficient.

They aren't cold, or unfriendly, or bad in any way. It just seems like they are there to do a job, and they do it. The phlebotomist made small talk about her hobbies, but there wasn't a lot of interaction. Dr. K asked all the right questions about my summer, if I traveled, about my kids. But I don't know it any of it really sank in. I get the feeling he won't remember any of it next time I see him.

Which is fine. I'm lucky to be at a place with my cancer where I feel like I can go in for my half hour appointment, get my blood tested, learn that everything is OK, and come back in six months. I don't need a best friend.

If I was actively going through treatment, maybe I would feel differently, and I'd need more emotional support. Then again, maybe I would like the efficiency -- "This is what the guidelines say, and this is what we're going to do." Let someone else make the decisions.

I'll be honest -- my wife worries about this relationship with Dr. K. She worries that, if anything happened to me, and she needed to make decisions about my health, she would have a hard time trusting Dr. K.

It's funny how, even when things are going well, we find things to worry about. Cancer sucks. Follicular Lymphoma sucks in particular.


But for now, we can put those worries aside. There's no sense in getting worked up about something that might not even happen. Like I've been doing for seven and a half years, I'll do my best to prepare for whatever possibilities might come down the road.

For now, I had a good check up today, and that's what matters. I'm going to have some ice cream to celebrate.

Friday, September 18, 2015

Follicular Lymphoma in Younger People

Hey all you youngsters -- diagnosed with Follicular Lymphoma before you were 40 years old -- the Annals of Oncology has some good news.

The median Overall Survival for younger patients is 24 years, and getting better.

Compare that to the median Overall Survival for FL patients, which, depending on the study, is anywhere from 8 to 15 years. That's a pretty good difference.

Of course, I was diagnosed about 6 months after I turned 40, so I'm not counted in this good news. (Which I am trying hard not be angry about.....)

 The study is part of a larger study of 1002 patients from four European Oncology Centers (Barcelona, Spain; Bellinzona, Switzerland; London, UK; and Novara, Italy) between 1985 to 2010. From there, they looked at 155 that were under 40.

They found that, after a median 10 year follow-up, they found the median OS to be 24 years. Keep in mind what "median" means -- half of the patients were below 24 years, and half were above it.

The study found some other things, too. Compared to older folks (over 40), the under 40's were less likely to have elevated LDH, high beta2-microglobulin, and high risk FLIPI scores (all signs of more aggressive disease). However, younger folks were more likely to have bone marrow involvement, bulky disease (larger nodes or infected organs), and disseminated lymphadenopathy (swollen nodes in several areas of the body) -- all of which are "bad," but not necessarily signs of aggressive disease.

Also compared to older folks, youngsters had a 10 year median OS of 81% (versus 51% for us older folks), and were more likely to have stable disease for longer.

Also, youngsters had longer Progression Free Survival and Cause Specific Survival if they were diagnosed within the last 20 years and have a low FLIPI score.

All of this is fantastic news.

With that in mind, here's some cold water: the conclusion to the study says " However, they still have a significantly shorter life expectancy than that of an age-matched general healthy population."

OK, that last part kind of stinks. But I'll take it. The overall message here is that Survival rates are getting better, not just for young people, but for all of us. And while, right now, we still have a shorter life expectancy than other folks, it's getting better. I have great hope that in 15 years (when I hit that 24 year OS), the landscape for treating Follicular Lymphoma is going to be so much different , so much better than we have now, that people will look back on my blog and giggle ("He thought about CVP? Ha! Was he a caveman?"). That's how much more advanced we will be.

Lots of good news here. As I've said before, I hate numbers and statistics -- except when they tell me something I want to hear.

Tuesday, September 15, 2015

Happy Lymphoma Awareness Day!

September 15 is honored every year as World Lymphoma Awareness Day, a movement begun by the Lymphoma Coalition. This is a world-wide initiative, which makes sense, since the Lymphoma Coalition is made up of Lymphoma-related organizations from all over the globe.

It always seems a little strange to talk about lymphoma awareness here, since the people who read this blog are probably the most lymphoma-aware people ever. (Be honest -- how many of you have ever stared at your lymph nodes, certain that they were getting bigger before your eyes?)

It's the rest of world, though, that's need some educating. Sadly, that includes some doctors. Last year's Lymphoma Coalition global survey found that 62% of lymphoma patients had been misdiagnosed -- doctors thought at first that it was something other than lymphoma. Clearly, the world needs some better knowledge about lymphoma.

The Lymphoma Coalition has some suggestions on their web site for what you can do to raise awareness. It's easy to spread the word online -- look at you, you're online right now, reading this. I'll bet you're on Facebook, Twitter, Instagram, or some other social media, too. Share some statistics, graphics, links, information -- anything to get the word out.

You have a personal investment in this matter.

Also, have some ice cream tonight. You deserve it.

Saturday, September 12, 2015

Blue Ribbons

Once again, my local New England-style agricultural fair is happening, and once again, my daughter and I entered various categories. I've seen this, in some ways, as part of my duty as a father -- encouraging her to test herself, live through a judging by others, and vow to do better next time.

Of course, writing it that way makes it sound like she doesn't do very well. That's not at all true -- she has won first place blue ribbons for her cupcake baking. cake decorating, clay sculpture, and jewelry making.

And I've done pretty well myself -- blue ribbons for two kinds of tomatoes and two kinds of muffins (plus some second and third place ribbons for other vegetable and for cupcakes). Not too bad.

But mostly, it's become a kind of barometer for my daughter -- a way to see where her head is. The first year we did this, she was 11, and she didn't take it very seriously. The second year, she spent all summer and did some really great stuff. The third year, she was a little busier, but still put in a great effort on a few entries, and did really well. This year? Well......


Before we get to that, we need to discuss MY results. I'm the cancer patient, after all, and it's my blog, so I'm really the most important thing. Skip to the next section if you want the sentimental stuff about my daughter.

First, vegetables, especially tomatoes -- nothing. Not only no ribbons, but I didn't even enter anything. I couldn't even find five decent tomatoes to enter. Or any other vegetable. The garden wasn't horrible this year, but it all really slowed down about three weeks ago. No more cucumbers or eggplant at all. Tomatoes are kind of all over the place -- a few ripe, lots of green ones in various stages of growth. But I need five of each variety, and I couldn't even find five that were in good shape, the same size, the same color. The fair is a week later than usual, and that had something to do with it, as did the last month and a half being especially dry. I thought about entering some swiss chard, but even that had lots of bug holes in it. I'll eat it anyway, but it wasn't pretty enough for the fair, so I didn't bother. That's the price I pay for not using lymphoma-causing pesticides, I guess...

I also entered some bread & butter pickles, nice sweet and sour slices. Last year, the pickle judges were pretty harsh -- only two entries, and no one got a first place, the other entry got a second, no one got a third, and I got nothing. This year, two entries again, with no first or second place. But I got a third. (And the other entry got nothing. Those judges are really had to please.)

Baking -- my chocolate cupcakes got nothing. They were once again under-appreciated.  By my fudge won a second place ribbon, probably because I added some bourbon to it. Next time I'll add a little more and hope for better.

My big success, though? My jam. My strawberry got nothing, and I'm not surprised, since there are usually lots of entries. But my big success for the night? A blue ribbon for my blackberry jam. Woo hoo!

This jam is kind of special. I have a shade garden in the back of my yard, and for the last few years, some thorny sprouts have been coming up, and I've been pulling them. Last year, after i had shoulder surgery, I couldn't do any yard work, and those thorny sprouts just kept growing. And then flowering. And then bearing fruit. Turned out they were blackberries, probably left there by birds or squirrels a few years ago.  This year, knowing that we had blackberries, I just let them grow -- no extra water or fertilizer, just whatever happened. And we got a ton of blackberries, enough for cereal in the mornings and dessert in the evenings for a few weeks, plus a big batch of blackberry jam. And that jam won a blue ribbon. Very satisfying.


And as for my daughter?

She certainly didn't put in the effort she has in years past. She still likes to sketch, but now it's portraits of her favorite bands. And she still likes to sculpt, but it's mostly sculptures of the members of her favorite bands. She entered a drawing she had done a while ago and got a second place ribbon for it. And she entered a small sculpture she had done a while ago, and got a third place.  Not a lot of effort, to be honest, and it showed.

The place she did put some effort was in her decorated cake. But, to be honest, even that wasn't a huge effort. But it came out great. The cake decorating theme was "super heroes," and she made a Super Grover cake (he's the alter ego of Grover from Sesame Street; he's a well-meaning but not very effective super hero). I knew she was going to do well when she dropped off the cake and everyone working at the fair squeeled with happiness.

Not only did she win a blue ribbon for decorated cakes, but she also won "Best in Class" for all baked items:

That's pretty dang good.

So what does all of this say about my girl?

Well, I think it says this:

I think she's ready to move on from this stuff. She didn't do anything extra for the sketch and the sculpture, and really, as great as that Super Grover cake is, she didn't have to work too hard to do it. That's not meant to be a brag (though as a father, I'm certainly capable of that).

But she's not the girl she was three or four years ago, when she spent all summer planning and creating all the things she'd enter in the fair.

And of course, I wouldn't want her to be the same girl. I wish she'd maybe take the ear buds out and come out of her room a little more often than she does, but she's in a place where I'm glad she is at -- pretty self-confident for a 14 year old girl, aware of what she can do (and, with this cake, do pretty easily), but also willing to take on some challenges. She started high school a few weeks ago, and that's a whole new world, too.

Will she enter the fair again next year? Hard to say. It will be her last year in the "junior" division, so she may try one more decorated cake or pair of earrings. But if not, that's OK. I'm proud of how far she's come in the last few years.
It might be time for both of us to move her out of the "junior" division.

Monday, September 7, 2015

Transformed Follicular Lymphoma's Cell of Origin

The most recent issue of Blood journal includes research on Transformed Follicular Lymphoma ("Cell-of-Origin of Transformed Follicular Lymphoma"). As the abstract says, we really don't know a whole lot about transformation -- not enough to predict who might transform. This article describes research that attempts to change all of that.

The researchers looked at samples from FL patients that had transformed, and some that had not, including some that they had samples from before and after their transformation. This allowed them to see changes in the cells, so they could determine what was different after transformation. They looked for known biomarkers -- elements of the cell that are present that signal something important.

What they found was that the biomarker IRF4 was a "predictor of early transformation." IRF4 stands for Interferon Regulatory Factor 4. The gene related to IRF4 does what its name says -- it helps regulate interferons, which are very cool signaling devices in cells. When a cell is attacked by an outsider, it releases interferons, which let other cells know that they should put up their defenses. When there is a problem with IRFs, interferons stop doing their jobs, and attackers are allowed to run wild.

So if there's a problem with an IRF, the body isn't stopping out-of-control cells from growing. Makes sense that it would play a role in transformation.

The research made several other important discoveries as well, including "composite histology predicting favorable prognosis." The abstract doesn't provide any more detail, and I haven't read the entire article, but composite histology indicates two types of cells. I assume this means both Follicular cells and  transformed cells, and having both (rather than only transformed) is better news for a patient.

It will be interesting to see where research goes from here. There's plenty of work being done on targeting translocated genes like IRF4, and stopping whatever process it is allowing to happen. IRF4 is a "known biomarker" (and has been known for quite a while), so I'm guessing there is research already being done. Looking forward to seeing how it relates to transformed Follicualr Lymphoma in particular.

Tuesday, September 1, 2015

R-Squared: Phase II Trial Success

I've seen reports and articles on a bunch of Follicular Lymphoma research in the past couple of weeks, and I'm very slowly getting around to reading it.

Up first: results from a phase two trial of Rituxan and Lenolidomide (also know as Revlimid, making this combination R + R, or R-squared).

The combo has been around for a few years, and there has been some excitement in the lymphoma community about it, based on early results from the trial. The Journal of Clinical Oncology spells out the details in "Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)."

(Before I get to those details, check out the link and look at the Lymphoma Rock Stars in the authors' list, including John Leonard, Myron Czuczman, and Bruce Cheson. Damn. You know you're a Cancer Nerd when you see the authors list on a medical journal article and you squeal like a 14 year old girl who has seen that 5 Seconds of Summer, One Direction, and Fall Out Boy are performing live on the Grammy Awards telecast. And I say that as the father of a music-loving 14 year old girl.....)

Anyway, as the article explains, the trial compared Revlimid/Lenolidomide on its own with Revlimid combined with Rituxan (the R-Squared). The trial involved 91 patients, roughly half of them receiving each of the treatments. Revlimid/Lenolidomide on its own resulted in a 53% Overall Response Rate (20% Complete Response), while the R-Squared combo had a 76% Overall Response Rate, with 39% achieving a Complete Response.

The Conclusion to the phase II trial is that the R-Squared combination was successful enough to justify a phase III trial, with a larger number of patients.

These results were first reported in 2012, and have finally been reviewed by other experts to show that the results are as good as they seem. This is one of a bunch of studies on Revlimid and R-Squared that are going on now (here's another one). We won't see results from the phase III trial for a while, but we've seen enough people with positive results to call this an unofficial success.

Looking forward to it being official.