Tuesday, April 28, 2015

Rituxan vs Watch and Wait (Again)

A couple of months ago, I wrote that I thought it was time to move on from discussing the whole Watch-and-Wait vs Rituxan choice -- whether or not it is best to treat with Rituxan right after diagnosis, or better to wait until treatment is necessary (as I did). There has been so much research done on whether or not Watching and Waiting is the best choice, given how effective Rituxan is, with its relatively mild side effects. Lots of good reasons for choosing one over the other, though there was no evidence that one had a better Overall Survival effect than the other. I said it was time to move on to other things, since we weren't getting anything new.

And now, we have something new.

The journal Cancer has published a study that shows that getting Rituxan is more cost-effective over the life of the Follicular Lymphoma patient than Watching and Waiting. In other words, if you take Rituxan (with or without maintenance) soon after diagnosis, you'll spend less money on treatments if and when the FL comes back than you would if you had just waited until treatment was necessary. The abstract for the study is here, and a commentary on it from Cancer Network can be found here.


Of course, I have some issues with the study and its implications. I hope you weren't thinking this was going to be some kind of Final Answer to this issue.

The researchers conducted a statistical study using something called a Markov Model, which is a fascinating tool that allows for the complexity of a medical situation like having a Follicular Lymphoma patient have to have many treatments over a lifetime. I don't think I can really explain it in very simple terms, but basically, it measures how a patient is likely to do after receiving a treatment, what kind of options will be available when another treatment is necessary, what the likelihood will be of choosing one treatment over another, and moving on down the line. Statistically, of course -- all of the numbers and choices are based on what we already know about Follicular Lymphoma.

Anyway, the results of their modelling show that someone who receives Rituxan soon after diagnosis will likely end up paying $59,953 (Canadian dollars) for treatments over their lifetime. Someone who had Rituxan, plus Rituxan Maintenance would pay $67,489, and someone who watched and waited would pay $75,895. Again, these are based on statistical models: statistics show that someone who watched and waited would likely need another treatment in XX months or years, and that treatment would likely be XXX, and would be followed in XXX months by XXXX treatment. This isn't an actual single patient with exact treatment recommendations.

The study also measures (again, statistically) Quality-Adjusted Life Years (QALY). This is, again, how many years someone would likely live disease-free. It's a little bit complex -- it takes into account the partial years a patient in disease free. So using me as an example, I have lived 7 years and 4 months since my diagnosis. BUT, I have never actually been disease-free in that time, having achieved a Partial Response after Rutuxan, and then having various levels of waxing-and-waning disease since then. On the other hand, I haven't missed any work because of it. By some statistical measure, they can figure out how many of my 7.25 years are Quality-Adjusted Years. I assume it will be less than 7.25.

(That's a lot of statistics from someone who keeps talking about how much he hates statistics.)

The researchers found that Rituxan plus Rituxan Maintenance right after diagnosis gave 6.28 Quality-Adjusted Life Years, with Rituxan-only gave 6.16 and Watching and Waiting gave 5.71. (The difference is a matter of months.)

So either form of Rituxan, by these measures, beats out Watching and Waiting.

Before you start regretting your watch-and-wait decision (and let me clear: I do not), let's look at this a little more closely.

First, let me point out yet again that this is a statistical study. It is uses statistics based on what decisions people have made in the past to determine the outcomes. I think that matters -- a lot. I remember, many years ago, when I saw Dr. C the lymphoma specialist soon after my diagnosis (not Dr. R, my regular ol' oncologist), he told me that anything I read on the internet is already out of date. I thought of that as I read this: this is based on treatment decisions (and costs) that were available at the time of the study. They can't really anticipate that, in 10 years, some super combination of monoclonal antibody, kinase inhibitor, and anti-PD1 treatments will be available, and will help 75% of patients, and cost less than Rituxan costs now. They can guess at that, but they can't really know. They can only know that after Rituxan Maintenance, a patient is likely to try Rituxan, and that will cost X, and then will become Rituxan resistant, and will try straight Bendamustine, and that will cost X, and so on. So like most statistical models, this is based on a bets guess (and admittedly, that is sometimes a frighteningly good guess).

I think it also matters that this study takes place in Canada. It could have been the U.S., or Brazil, or the U.K., or New Zealand. Whatever. It's in one specific place at one specific time. That's going to have a significant impact on the cost of treatments, but also the availability of treatments (as the Lymphoma Coalition's Report Card makes very, very clear). Change the time and location, and those statistics are likely to change. That may actually favor Rituxan, as its trademark protection expires, at least in the U.S. Though it may favor Watching and Waiting, too, in other places where treatments are more costly.

I said it in the last post I wrote about this debate, linked above, and I'll say it again: There is a lot that goes into the initial decision on a treatment after diagnosis. Cost certainly matters. Physical state obviously matters. But so does emotional state. As much as we can learn from past statistics, and as much as it would be great to consider what future treatments might be available, what matters to most of us, at that time, is what is happening RIGHT NOW, at diagnosis.

So I think this study adds some interesting stuff to talk about. But I maintain my power as Lympho Bob to say: this debate still isn't settled. Talk to your doctor about every factor that might play a part in making your treatment decisions.

Friday, April 24, 2015

Copanlisib for Follicular Lymphoma

Last week (yes, I'm still catching up), the manufacturer of Copanlisib announced that it was expanding its clinical trials, with two new phase III trials for indolent lymphoma and one new phase II trial for DLBCL. This is good news (assuming enough people sign up for the trials, of course).

Lots to unpack here.

Copanlisib hasn't been in the news much, at least not the news that I have been reading.  First off, let us note that Copanlisib is a pan-class I phosphatidylinositol-3-kinase (PI3K) inhibitor. Kinase inhibitors are a type of treatment that has certainly been in the news lately for Follicular Lymphoma and other lymphomas. These are "pathway treatments" -- they don't attack the cancer cells directly, but block the pathways that help cancer cells develop, grow, and multiply. PI3K inhibitors work by blocking signalling pathways in cells. That is, before a cell can grow, it needs a signal from somewhere else down the pathway. Cancer cells get that signal, but keep on growing.  A PI3K inhibitor keeps that signal from reaching the cell. No signal, no growth. No growth, no cancer.

Now, there is another PI3K inhibitor already approved out there -- Idelalisib. From what I can tell, Idelalisib and Copanlisib will work through slightly different mechanisms, and will target slightly different pathways. Basically, kinases are proteins, and they come in different forms. Idelalisib targets the "delta" form of the protein, while Copanlisib shows activity against both the "delta" and "alpha" forms. So maybe there is a chance that they will work together, or compliment each other in some way.

Copanlisib has already shown some good activity in indolent lymphoma. At the ASH conference a few months ago, results from a phase II study showed that, in 33 patients with different types of NHL (including 16 with Follicular Lymphoma), all of whom had already been given several treatments, almost half had a response. For the Follicular Lymphoma patients, 1 had a Complete Response, 1 had an unconfirmed Complete Response, and 5 had Partial Responses, for an Overall Response of 47%. Not too bad.

Those same patients will be the target group for one of the phase III trials announced last week.

So, this is good news. Another potential arrow for the quiver, as they say -- another possible way of attacking this disease. But in a targeted manner.

Of course, we are still early in the process. As Karl from Lymphomation.org has pointed out before, we have lots of potential new treatments out there in various stages of the pipeline, and that is certainly something to cheer. But unless we get enough people who are willing to be a part of the clinical trials for those treatments, we won't really know just how effective they might be.


Tuesday, April 21, 2015

Follicular Lymphoma & Hope

The Leukemia and Lymphoma Society has put a few new videos online in the last couple of weeks. They tell the stories of lymphoma patients and, of course, how they were helped by LLS (and how viewers can help, too).

The first one I saw was about a woman named Yolanda, and it's an emotional one. She says the first thing she thought about was her husband and her son and daughter. There are a few tears in this one, and that's one of the reasons I like it -- she really conveys the emotions that come with a diagnosis. She calls cancer a "dirty word," which I love. Yolanda received R-CHOP, and she raises money for LLS through a Light the Night team.

One thing I didn't like about the video, though, was some of the implications. She mentions that she was diagnosed at stage 4. Now, given that she doesn't give a grade, it's hard to know if she had a particularly aggressive form of FL. She also mentions that she is coming up on the 5th anniversary of her remission. That matters, too. Both of those things (stage 4, and 5 years in remission) don't really mean the same thing for FL as they do for most other cancers. Because Follicular Lymphoma is systemic (that is, the cancer cells travel all over the body), stage doesn't really matter as much as it would for other cancers. Grade would make more of a difference. Same with the 5 year remission. For many other cancers, that anniversary means a drastically smaller chance of the cancer coming back. Not so for Follicular Lymphoma.

The other video was about a man named Jeff, also diagnosed on the young side (51), and who had his family to think about. He went in for a his annual check-up, found a lump under his arm, and was diagnosed with FL. But what he has to say is this: "My diagnosis was Follicular Lymphoma. And what that basically means is, there is no cure."

To me, that second video sends a very different message.

I'm not saying the LLS is being dishonest in the first video. I understand that their job is to get people to donate money, and there's kind of a conventional story that gets people to do that: Young person, bad diagnosis, successful treatment, things look good, you can help too. They sell hope that way.

But to me, that second video gives us a much more realistic version of what hope is, at least for those of us with Follicular Lymphoma.

Jeff goes on to talk about reading everything he could online about FL, and how he found the LLS, and read about the research they did. He goes on to talk about how he was inspired to raise money for research.

His wife says, "This is going to sound odd, but this is the most exciting time to have cancer." Why? "Because the innovations and the treatments are just through the roof....To see that gives me tremendous hope that, in the next five years, they're going to come up with something for my husband."

And that sums things up pretty well. In fact, her two sentences can sum up the entire Lympho Bob blog, all 1000+ posts. I should stop writing and just set up a web site that says that: "This is going to sound odd, but this is the most exciting time to have cancer, because the innovations and the treatments are just through the roof. To see that gives me tremendous hope that, in the next five years, they're going to come up with something for me and other Follicular Lymphoma patients."

Maybe it's those darn numbers in the first video that bother me -- stage 4, 5 years. Numbers fix things in time.They seem so exact. I'll take the not numbers, the possibilities, the future, the hope. I've learned to live with the uncertainty. With uncertainty, you're much less disappointed.

It all reminds me of a poem by Emily Dickinson:
“Hope” is the thing with feathers -
That perches in the soul -
And sings the tune without the words -
And never stops - at all - 
 
For me, hope is the thing without numbers. 
And the rest of that poem holds true.

Friday, April 17, 2015

Follicular Lymphoma Treatment Selection

The site OncLive sponsored a"Peer Exchange" that was posted online this week. The discussion is a series of videos, focusing mostly on CLL (Chronic Lymphocytic Leukemia, a slower-growing type of leukemia). Toward the end of the series, they begin to discuss other types of NHL, including Follicular Lymphoma.

In fact, I think they are releasing these videos one at a time, with some time in between. The two that focus on FL get cut off abruptly at the end. Still, there's some interesting stuff there.

Leading the discussion in the first Follicular Lymphoma video is Dr. Myron Czuczman from Roswell Park Cancer Institute. Interestingly, much of what gets discussed has to do with chemotherapy: R-CHOP, R-CVP, F-R, and Bendamustine + R, and particularly the trials like BRIGHT that have compared different types of chemotherapy. The oncologists in the exchange (especially Dr. Czuczman) seem pretty invested in chemotherapy. At first that was a little off-putting to me. I see the value in comparing traditional chemotherapies, but I think there are much more interesting things awaiting us in the future.

And, stepping back a bit, I can see that the panelists do discuss some of those current/future treatments for Follicular Lymphoma: Idilisib, Ibrutinib, and Revlimid. And they ultimately seem to favor Bendamustine over other, more traditional chemotherapies like CVP and Fludarabine, while recognizing that those treatments do have a place in certain situations.

But the big difference between more traditional chemos and those sexy new treatments is that the more traditional ones have a track record of success -- in the case of CHOP, a record that is decades long, Dr. Czuczuman reminds us. With CHOP, we have a pretty good idea of what we're getting, good and bad, short- and long-term. With something like Idilisib, we're going on some very good short-term results. And really, the same is true for Bendamustine. As superior as it seems in trials that compare it to other treatments, we don't know what the effects are over the very long-term.

So, yes, that's a good reminder (for me, who gets excited about all the new stuff out there) that traditional chemotherapy still has a place in Follicular Lymphoma.

The second video looks at some of the treatments that seem effective for CLL, and asks how well those might work on Follicular Lymphoma. It's a shorter video, and makes an important point: as exciting as things have been lately for CLL (and the last two years have been awesome), CLL and FL are different diseases, and treatments will work differently on them.

One other thing that seems exciting, besides Bendamustine, is R-squared (Rituxan + Revlimid, also known as Lenalidomide). Early results from a trial looked great, and the panelists anxiously await more results for this promising combination.

So, overall, I think these videos tell us some interesting stuff, about the past and maybe about the present. But I still would rather hear about the future. As great as it is to know that R-CHOP is there if my FL turns aggressive, I still get more excited thinking about all of the research we are seeing about the genetic basis for cancer, and about pathways and microenvironments. As great as R-CHOP is, something "decades old" doesn't (and can't) take any of that into account.

So it's nice to know R-CHOP and B-R are there for me now. But I want to know what's waiting for me in the (hopefully near) future. And "hope-fully" is the key word there.

Myron Czuczman

Saturday, April 11, 2015

Dancing My Cancer Away

Last night, I spent a wonderful evening with a lovely young lady: my 13 year old daughter. We went to her school's annual Father-Daughter Dance. The first time the school held it, she was 3 years old. We have been to every one of them (something we share with only one other father-daughter pair. We have our ritual: we go to dinner first, my daughter in a new dress, and me in jacket and tie (always a  tie that matches her dress). I buy her a corsage. When she was smaller, the waitresses would always make a big deal over her (the corsage as big as her head let them know it was a special night).

It's always a fun night. There are lots of little girls there, 3 or 4 year olds from the pre-school class, dancing with their dads, which brings back nice memories. (I can't pick my daughter up for the slow dances anymore). And there are girls of all ages, up to 13 or 14, like my daughter. They don't dance with their dads quite as much as the younger ones do -- the teens are usually in a group, off in a corner, talking about something or other, while their dads line the wall and check the Yankees or Red Sox scores on their phones.

Except for MY girl, who did hang out with her friends a lot, but who also made sure that when the DJ called for a father-daughter dance, she and I danced. And boy, do we dance. (I hate to brag, but at one point, the DJ asked the girls to teach the dads how to dance. And then he switched songs to Michael Jackson's "Billie Jean," and asked the dads to teach the daughters. And he gave prizes to the best dancers. And yes, I won a prize. It was a Taylor Swift t-shirt, but heck, I can add "award-winning dancer" to my list of accomplishments. Of course, when we danced "The Robot" a few songs later, he offered us another prize if I promised to STOP dancing.....)

And as always, the evening ended with the song "Butterfly Kisses." My daughter held me tight as we danced. That was pretty nice. Especially seeing some of the other teen girls ignoring their dads.

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I used to write about my kids a lot more than I do now. When I did it in the early days of the blog, if was because most of the people reading were friends and relatives, and the blog was a way of keeping them up-to-date about what was going on in my life, cancer-related and not. And then a bunch of things happened: Facebook came along, and my wife posted lots of news about the kids, so they didn't need to read my blog for pictures and videos. And then more people started reading the blog, people who weren't family and friends (at least, not the kid of friends who knew my kids). And my kids got older, and they didn't necessarily want their business put out on the web. So I stopped writing about them so much.

But they haven't stopped being awesome, by any means.

My daughter, as you can tell, is growing into a beautiful young woman. She's off to high school next year, which is a big change for her. But she's smart, and friendly, and talented. She loves to sing (had a good juicy speaking and singing role in her school musical this year). She still loves to bake and sculpt. And she's a good kid.

My middle son is in high school. He's our scientist. He's had a love of animals since he was a toddler (when we went for walks in the neighborhood, he would make us walk around ant hills so we didn't step on any). He still has that love of the natural world, and joined his school's team in a state-wide competition on environmental knowledge and problem-solving. With his help, his team placed 8th in the state, up from 23rd the year before. He's a straight-A student, plays oboe in the school band, and plays on his school's ultimate frisbee team. And he's really funny.

And my oldest has even more to brag about. He's a senior in high school, and made his college choice last week. He'll be off next year to a university that is perfect for him, in a vibrant city, with lots of opportunities. He's been on the school's Facebook site, making friends, connecting with people who want to start a band, who share his interests, and who are as excited as he is about their futures. He will have opportunities to learn more about his wide variety of interests, but for now, he plans to study music. He plays lead alto saxophone in his school's jazz band, along with soprano sax, flute, and clarinet, plus bass in another jazz band, and he's been known to beat out a rhythm on piano or drums if someone is desperate for help. He's tried his hand at arranging and composing, too. And he and some friends have a small jazz combo that plays cocktail parties and other events. We are immensely proud of him, and very excited about where he will go from here.

This is him playing sax on Count Basie's "Lonely Street" at this year's Berklee High School Jazz Festival:


And they're all really good kids. They don't give us much trouble -- nothing that would make the evening news, anyway.

************************************

I'm not saying all this to brag (at least, not JUST to brag).

Last night, when I was dancing with my daughter to "Butterfly Kisses," I started to think back about where I was seven years ago, when I was diagnosed. I've written about my kids before, and how hard it was to have to tell them I had cancer. And how dark things were then, worrying about my kids.

I remember, at one point, thinking that if I could just have 5 years, that would probably be OK. At that point, my kids would have been 16, 14, and 12. Not a great age to lose their father, but maybe better than being much younger. I remember the Father-Daughter Dances being especially important to me then, worrying if the next one would be the last one.

And I wonder if my daughter's tight hug during "Butterfly Kisses" comes from her having the same memories, and feeling the same things.

Sometimes I hear stories about people with terminal cancer who felt blessed to see their kids reach some milestone -- a graduation, or a wedding, or the birth of a child.

I don't think in those terms anymore.  And I don't worry as much. Time helps to re-adjust the mind, but I also know that with every day, with every new treatment, we're a step closer to beating This Thing, or at least controlling it.

For now, I just enjoy the dance.

Wednesday, April 8, 2015

Talking with Your Doctor

So I'm off to see my new oncologist in a few weeks. And I'm trying to find some time to think about what I want him to know about me, beyond what he will see in the chart, and what kind of a relationship I want to have with him. So I've been reading advice about what to do when you first meet your oncologist.

Which is really weird. Here I am, a veteran cancer patient, and I'm looking at the kind of sites that newcomers have to read. I should know all of this stuff already, right?

But it's interesting -- I'm finding that I probably got so comfortable with Dr. R that I stopped doing some of the things that I should have been doing to make sure he and I communicated well. So maybe it's a blessing that I have a new oncologist. It's kind of forcing me to remember how to be a patient.

I found a nice, but brief video from Patient Power, posted about 6 weeks ago, that gives some advice on how to bring up issues with your doctor. It's pretty good advice, and definitely stuff I haven't really done in a while.

Basically, it's about being honest with your doctor. And that's hard sometimes, even if it isn't intentional. We say our pain level is lower than it really is, because we don't want to sound like a whiner. Or maybe we're having a symptom that's a little embarrassing.

(I have to say, nothing much embarrasses me anymore. I'm not an exhibitionist, but these days, I'll drop my pants for anyone with a stethoscope. I've seen so many doctors and nurses, chances are good that the one in front of me has already seen all that I have to offer anyway.)

But other things can help, too, in making sure that the doctor hears everything she should: having a friend come along to ask questions and give reminders (my wife is great at that); writing stuff down,  in lots of detail, so you can remember symptoms and pains and feelings (physical and emotional). This makes sure everything gets covered, especially when your time with the doctor is short, and ultimately makes you feel empowered -- that you are taking control of the time that you do have.


So, will I do all that with my new oncologist?

I hope so. I hope my life will slow down soon enough that I can think about all of the things I want him to hear. For now, I don't have time to even write some short notes, let alone any blog entries....