Thursday, March 5, 2015

Immunotherapy Basics

I've linked a few times to a site called Yale Cancer Center Answers, and I'm going to give you another one.

"Answers" is a local radio show, sponsored and produced by the Smilow Cancer Center at Yale-New Haven Hospital. The show is hosted by oncologists, and every week, they have a different cancer-related topic, and interview an expert in that area who is affiliated with Yale. Shows range from specific types top cancer to information for caregivers to nutrition and exercise advice.

A recent show was titled "Using Immunotherapy to Fight Cancer," and that title certainly caught my eye. If you have kept up with cancer news in the last couple of years, you know how important immunotherapy is for our future. As researchers have learned more about cancer, they have come to understand how it resists attempts by the immune system to control it. In other words, cancer doesn't belong in the body, and the immune system is supposed to take care of stuff that doesn't belong. Immunotherapy involves the many ways that researchers are trying to fix that situation, training the body to recognize and eliminate cancer cells. Think PD-1, which has been in the news. PD-1 stands for "Programmed Death"; it appears on the surface of cells and prevents T-cells from killing the cancer cells. One class of cancer treatments making lots of news is PD-1 Inhibitors, which shut down PD-1 and let T-cells do their job and wipe out the cancer cells. Immunotherapy -- allowing the body's natural immune system to take care of the cancer.

The Yale show features an interview with Dr. Tarek Fahmy, who teaches Biomedical Engineering and Immunology at Yale. In the interview, he describes Immunotherapy in general, using vaccines as an example. A vaccine for something like measles works because it trains the immune system to recognize measles and attack it. Immunotherapy engineers try to build the pieces that go into that reaction and get the various parts to talk to each other.

It works the same way with cancer cells, as Dr Fahmy discusses, though it's a little tougher because cancer cells are so tricky.

Overall, it's an interesting interview. Yale always does a nice job on this show of explaining difficult ideas in easy-to-understand ways. In this interview, you'll find comparisons to brewing beer, Pac Man, and hair follicles, among other things.

You can find a recording of the show here and clicking in the January 25 link, and a written transcript of it here.


Monday, March 2, 2015

Watching and Waiting is OK (And Now It's Time to Move On)

The British Journal of Haematology has an article coming out that focuses on Watching and Waiting in advanced stage, asymptomatic Follicular Lymphoma patients. Patients who are kind of like I was -- stage III, some swollen inguinal nodes, but otherwise feeling fine. The study looked at 286 stage III or 4 Follicular Lymphoma patients (in Denmark, I think, since that is where the researchers are from).

I'll spare you the suspense -- the conclusion of the article is "advanced stage FL managed by WAW had a favourable outcome and abandoning this strategy could lead to overtreatment in some patients."

There are a bunch of statistics, too, though they don't mean much without comparing them to patients who had other treatments. Also, they don't mean much because they are statistics, and statistics might give us a sense of trends for a group of people, they say nothing about us as individuals. I've said it before, and I'll say it here again -- any time I've gotten depressed about my cancer, it has been because of statistics. So I'm not going to say anything about them here.

The important thing is that conclusion -- that Watching and waiting is still a valid strategy. Having been a watch-and-waiter myself, I appreciate hearing that I made an acceptable choice. If I had chosen differently, that would probably be OK, too -- there's nothing I can do to change the past. We all make out choices best on the best information we have available to us. I'm guessing if I hadn't chosen Watch and Wait, I wouldn't spend so much time reading and writing about it. I'd just have moved on.

And moving on is just what I think we should do with the question of whether Watching and Waiting is a valid strategy for this FL population. It seems pretty clear to me that we aren't going to have a clear answer to the question. We have some studies that say it's not worth doing, because we have a clear alternative in Rituxan (and may have a few more in the next few years as more monoclonal antibodies become available). And we have some studies that say there isn't enough of a difference between Watch-and-Waiters and patients who are treated immediately to say Watch and Wait isn't valid. The most recent was a study from Japan, presented at this year's ASH conference a few months ago.

So I'm using my power as Lympho Bob to demand an end to this debate. It's time to move on. Let's focus on those exciting new treatments in the pipeline, train oncologists to get a sense of the whole patient at diagnosis -- her emotional state as well as her physical state -- and involve the patient in deciding the best course of treatment.

Having lots of options is one of our strengths. Let's do our best to make sure patients get all the options they can, and choose the one that they need.

There. It's decided.

Friday, February 27, 2015

Follicular Lymphoma and Anxiety

The Journal of Clinical Oncology published a study a few weeks ago called "Anxiety and Health-Related Quality of Life Among Patients With Low-Tumor Burden Non-Hodgkin Lymphoma Randomly Assigned to Two Different Rituximab Dosing Regimens: Results From ECOG Trial E4402 (RESORT)."

As that very long title suggests, Follicular Lymphoma patients were divided into two groups. Both received four rounds of Rituxan, and if they responded, one group received Rituxan Maintenance, and the other Rituxan only after their lymphoma had progressed enough that it was necessary. The patients were given surveys to measure how much anxiety they had at various points along the way. they were also classified by the way they coped with their disease -- either through "active coping," or "avoidant coping."Active coping basically involves doing something -- either trying to change your the thing that;s causing you stress, or change your attitude about it. Avoidant coping is basically doing nothing -- trying to put it out of your head and hope it just goes away. As you might guess, psychologists think active coping is a better choice.

The researchers found some interesting things: anxiety related to their illness was about the same for both groups. Anxiety decreased over time for both groups. And Overall Quality of Life didn't change much over time. I think that has a lot to do with when all of this was measured -- AFTER that first treatment with Rituxan. It would be interesting to see how much anxiety there was for patients who watch and wait BEFORE they have an initial treatment.

I thought it was pretty interesting, too, that anxiety decreased over time. This isn't surprising. In my experience, and in conversations with other FL patients, I'd say it takes about six months after diagnosis to start to feel better, especially for watch-and-waiters. I think for many of us, we hear that word cancer and imagine the worst. It takes a while for it to sink in that we aren't going to die tomorrow, at least not from FL. (I should make clear that the patients in this study, like me, had low tumor burden, and so their FL was not as aggressive as it is for some others.)

One other important bit from this study: patients with avoidant coping styles were much more anxious than those with active coping style. In other words, pushing your problems away probably isn't going to make you feel better. I tell my kids this all the time -- you can try to pull the covers over your head and stay in bed, but all the only problem that will solve is a lack of sleep. Eventually, you're going to need to get up and deal with things.

The good news is, you are most likely all active problem solvers, or you wouldn't be googling "Follicular Lymphoma," or reading, or joining an online support group or a Facebook group -- however it is you first came across a link to this blog, you were doing something active to help you control your anxiety and learn more about your disease.

It's a better strategy, and I hope you are better for it.

Monday, February 23, 2015

Hematologic Malignancies Conference

A few days ago, the 2015 Congress on Hematologic Malignancies took place in Miami, Florida. This isn't a conference like ASH or ASCO, where new, cutting-edge research is being presented for the first time. Instead, it's a gathering of clinical oncologists -- the folks who take care of us directly -- meeting up to get practical advice on how to help patients.

(They were probably also hoping to gather someplace warm to escape the horrible winter that has hit most of the U.S. Not too bad there -- high 60F is better than what most of them probably left behind them at home.)

It's a small gathering, with just a few sessions (compared to something like ASCO, especially), so there isn't a whole lot of news about it online. But OncLive has done interviews with the people who are presenting, and one of the interviews is with Dr. Myron Czuczman from the Roswell Park Cancer Institute. He presented on sequencing therapies for Follicular Lymphoma. In other words: we can assume most of us with FL will need a series of treatments. So which one do you do first, and what comes after that? And that?

Myron Czuczman, MD, chief of the Lymphoma/Myeloma Service and head of the Lymphoma Translational Research Laboratory at Roswell Park Cancer Institute - See more at:
Myron Czuczman, MD, chief of the Lymphoma/Myeloma Service and head of the Lymphoma Translational Research Laboratory at Roswell Park Cancer Institute - See more at:

The brief article doesn't go into too much detail, but I found it encouraging to know that oncologists are thinking carefully about the issue. And it was interesting to see, even in a general way, what some of the issues are that have to be considered. As Dr. Czuczman says, there is no recipe to follow -- at every step, there are choices to be made. That's good for all of us to remember. (It also makes things more complicated, of course.)

One other thing that Dr. Czuczman does point out is that the choice of treatments should consider side effects and quality of life. While he doesn't say it specifically, I think it's worth remembering that quality of life involves the emotional factor that comes with being a Follicular Lymphoma patient. Obviously, every cancer patient deals with emotions. But ours are a little bit different -- many of us have to decide if we will be willing to hold off on receiving treatment. That's above and beyond the other emotions that we have when we are diagnosed.

So, I hope everyone who attended the Congress had a good time, maybe warmed up a little, enjoyed some seafood, and learned something new about blood cancers.

Wednesday, February 18, 2015

Memory Games and Lymph Nodes in Follicular Lymphoma

The Hematologist, a publication of the American Society of Hematology, published a piece last week called "Memory Games in the Lymph Node: The Inflammatory Origins of Follicular Lymphoma." It's a pretty dense article, but I think it says some interesting things about where Follicular Lymphoma comes from -- and, of course, that could provide some clues for how to get rid of it.

The author, Dr. Peter Johnson, reports on a series of experiments by French researchers. Dr. Johnson begins with some basic physiology about FL: it involves BCL2, which keeps cells from dying a natural death, and involves a build up of two kinds of cells: Follicular Lymphoma In Situ (FLIS), which accumulate in the lymph nodes, and  and Follicular Lymphoma-Like Cells (FLLC), which travel in the blood. These cells eventually become full-blown FL.

A particular genetic translocation (in other words, a switching of genes) is very common in FL (known as the t(14;18) translocation). However, this translocation also occurs in people without Follicualr Lymphoma. The question, then, is what makes things go wrong? Why do those FLIS and FLLC cells turn into cancer?

The French researchers used a mouse model to try to figure this out. Mice can serve as pretty good "model organisms" -- substitutes for people while researchers try to figure out how something works. We might not like to admit it, but mice are actually pretty close to people in terms of genetics; we share of 95% of our DNA. So using mice as models for genetic causes of cancer makes sense.

The researchers used a mouse with a human BCL2 gene that is only activated during something called V(D)J recombination. This is a very specific process that happens when an immature blood cell is turning into a specialized blood cell -- it is basically finding out what job it needs to do for the body. This is also the time that things can go wrong.

So basically, we have a mouse that is set up in a way that mimics how humans might get Follicular Lymphoma, if the right circumstances come along.

Next, the researchers introduce the right circumstances.

Over nine months, the researchers made the mouse produce antigens -- basically, reproduce those B cells that can get messed up. And, of course, the B cells got messed up. They found FLIS cells in the lymph nodes, and found that lots of memory B cells had problems. This is important -- memory B cells are the cells that hang around after the body has fought off an invader, to remind the body of how to fight it off again, the next time that invader returns. So now we cancer cells, which have had their "natural death switch" turned off, hanging around the body. Not good.

And it gets worse. When an immune system cell (like our B cells) pass through a "germinal center," located in places like lymph nodes, they sometimes get changed from one type of immune cell to another, depending on the body's needs. This is a normal thing, meant to help protect us. The problem is, Follicular Lymphoma cells that go through germinal centers tend to have a lot more changes than normal B cells.

So here's where we are: we have a bunch of B cells in the blood that are waiting for the right circumstances to turn into Follicular Lymphoma. Those circumstances happen. The cells go through germinal centers are change form in lots of ways, enough changes that the cells turn cancerous. And the ones that are special memory cells, meant to hang around in the blood, do just that. Ugh.

So what does all of this mean for you as a patient? Well, nothing, as far as your next oncologist appointment goes. But it does say something about how we might understand the origins of Follicular Lymphoma. For example, Dr. Johnson says that the study "would suggest that recurrent or chronic immune stimulation could provide an important predisposing factor for FL." Lots of activity for those B cells, changing to adapt to problems, might make one more likely to get Follicular Lymphoma.

But like everything else, this is still speculation. And even if it is true, it's a matter of predisposition -- making it more likely, but nor guaranteed.

This is a tough article to get through, and looking back at this post, I'm not sure I did much better at explaining it than the original did. What's important is that researchers are continuing to find out more and more about our disease at the genetic level, and at some point in the future, that's going to translate into a way to make us better.

Sunday, February 15, 2015

Obinutuzumab in Indolent NHL

The maker of Obinutuzumab has announced that a phase III trial has been stopped because were good enough to seek approval from the FDA for indolent NHL.

Obinutuzumab is a fully-humanized monoclonal antibody. In other words, rather than using mice cells in its manufacturing, as Rituxan does, Obinutuzumab uses only human cells. The idea is that the human cells might cut down on some of the allergic reactions that Rituxan can cause.

In this phase II trial, researchers looked to compare Obinutuzumab + Bendamustine with Obinutuzumab maintenance, with just plain ol' Bendamustine. They hoped to see some improvement
in Progression Free Survival, and in looking at 413 patients, they found some. They plan to announce the specifics soon.

Obinutuzumab is seen as an alternative to Rituxan. From a business standpoint, since Rituxan's patent protection will expire soon. While generic versions of Rituxan are expected to be available, there may be some patients who will switch to Obinutuzumab instead, especially since a number of studies (including this one) seem to suggest that Obinutuzumab will work on patients who have become resistant to Rituxan.

The landscape for Follicular Lymphoma is certainly changing. We're going to have quite a few choices -- even more than we have now -- in the very near future.

Wednesday, February 11, 2015

Good News for R Squared (Revlimid and Rituxan)

Lymphoma Hub is reporting good news on results of a clinical trial of R-Squared (Rituxan + Revlimid, also known as Lenalidomide).

Actually, it's great news: Adding Revlimid to Rituxan seems to overcome Rituxan Resistance.

The trial involved 43 patients with different types of indolent lymphoma, including 26 with Follicular Lymphoma. About half were resistant to Rituxan, and the other half or so had relapsed after Rituxan treatment within six months.

Patients received Revlimid every day for 8 weeks. They were then given Rituxan once a week for four weeks. The Overall Response Rate after the Revlimid was 30.2%, which is pretty good. However, adding Rituxan again was even better --  after 12 weeks of letting after letting the Rituxan do its job, the ORR was 62.8%, more than double. Clearly, the Revlimid did its work. Patients in the trial started out resistant to Rituxan, and ended up having it work again.

The results for the patients with Follicular Lymphoma were even better. The ORR after Revlimid was only 19%. But after Rituxan, it jumped to 65% -- more than triple.

R-Squared (or R + R) has been in trials for a while, but according to Lymphoma Hub, this is the first trial to report results. I think they give us a lot to be excited about.

Of course, this is a small study. And then, there are the side effects that come with Revlimid (see the article for more on that). But I think this is a good example of the kind of combination therapy that we'll see more of in the future. We know how complex cancer is, and attacking it from different angles.

I'm sure we'll see more about R-Squared in the future.