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.