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 C told me a long time ago, anything you read online about Follicular Lymphoma is already out of date.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.

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.

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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.

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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.

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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.

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. 

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.

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.

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.