Thursday, October 29, 2015

Immunotherapy Explained

Lymphomation.org'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: http://www.cancernetwork.com/oncology-journal/targeted-approaches-management-follicular-lymphoma#sthash.yijmoBYx.dpuf

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/ Lymphomation.org: 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 Lymphomation.org 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 Lymphomation.org 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.....
obinutuzumab
obinutuzumab
obinutuzumab

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.