Every now and then, when I'm doing research on Follicular Lymphoma, I'll come across a report from a financial firm that discusses how a particular lymphoma treatment is going to have an effect on the company's stock price. Most FL treatments are offered by large pharmaceutical companies, and it seems like smaller companies that develop new treatments will partner with bigger ones or sell the rights to a treatment to a big one. Our health is a big business. There's no way around that.
I came across one of those articles this morning -- "B-Cell Non-Hodgkin’s Lymphoma Treatment Market Will Stutter to $5.45 Billion by 2024, says GlobalData" -- published by ETHealthWorld.com. I'm no finance expert, so I can't say how accurate the report is, but I think it raises some interesting questions for us as patients.
According to the report being discussed in the article, the value of the B-Cell Lymphoma treatment market in 2014 was $4.35 billion. It is expected to reach $5.45 billion by 2024. That represents a compound annual growth rate of just 1%.
In other words, if you were hoping to make some money by investing in companies that produce treatments for B-Cell lymphomas (including Follicular Lymphoma, but also including a bunch of other lymphomas), you probably aren't going to make much.
Now, I personally don't have any extra money to invest (that's what happens when you spend your free time researching and writing a blog but you're too dumb to attach sign up for Google Ads to make a little money off of it). I'm much more interested in what the analysis might mean for my health.
According to the report, the growth is going to be very slow in seven major markets: the US, France, Germany, Italy, Spain, the UK, and Japan. One big reason is because Rituxan's patent in the US will expire in September, and a biosimilar should be available in all seven countries by 2018. This means that biosimilar versions will be allowed to be sold -- stuff that isn't officially Rituxan, but that was made in the same way and that will (or should) act the same way, but for less money. (It will cost less because they companies making the biosimilar didn't have to spend all of that money researching and developing and marketing Rituxan.)
The article also points out that Bendamustine and Lenalidomide will have generic versions introduced in those countries at different times between now and 2024. (I don't have information about when that might happen.)
Finally, the report says that "no late-stage drugs in the NHL pipeline are expected to achieve
blockbuster status, as rituximab-based chemotherapy regimens are
gold-standard therapies that dominate the NHL treatment algorithms
across both indolent and aggressive forms of the disease." To be clear, this doesn't mean that there are no new treatments becoming available soon -- there are lots of them. But there are no "blockbusters" -- no treatments that will overwhelm everyone and have oncologists insisting that everyone has to take them and make investors lots of money. That's not a big surprise -- we can't decide what the best first treatment is for Follicular Lymphoma, even with the ones we have.
So what does that all mean for us as patients?
Let me say again, I'm no financial expert. And I'm not a medical doctor, either, so this is just guessing.
In the US, anyway, there is still lots of disagreement over health care, and the best way to deliver it for the least amount of money. (I know other countries have this same disagreement -- it costs a lot to stay healthy.) So I would guess that insurance companies or governments or whoever pays for health care in different countries will push the cheapest possible treatments. If biosimilar or generic versions of Rituxan and Bendamustine become available, does that mean that we will see B + R being pushed more often? That's not necessarily a bad option -- it's an effective combination, with less toxicity than R-CHOP. And we've seen lots of good stuff about Lenalidomide in the last few months. If that also gets cheaper in the next few years, and we keep seeing strong results from clinical trials, maybe we'll see some kind of R-squared + Bendamustine combination getting more popular?
Of course, this doesn't mean that other treatments won't become available, or that doctors won't prescribe them. But it might mean that those other treatments will need some help in showing how effective they are, and that means more patients signing up for clinical trials. I actually spent a little time a few days ago looking up trials that were near where I live. I found about 8 really interesting ones that I would qualify for. I don't expect to need treatment any time soon, but every now and then, I like to know what my options are. I learned about a couple of new treatments in the pipeline. It was a fun night in the Lympho Bob household. Hot chocolate and cancer clinical trials. (If you want to join in the fun, Lymphomation has lots of information and links to easy tools for finding trials.)
Because, really, the only way for anyone to know how good certain treatments are is to have them tested in trials. We may not like to think about it, but our health depends on other peoples' money. Some people have to make money in order for a treatment to become available. Other people have to save money in order for treatments to get to us. We're stuck in the middle. The least we can do is help make more treatments available and give them something to fight about.
As I said, all of this is guessing, certainly from me, but really, also from the financial analysts who are trying to figure out how to make money off cancer. They can only guess about how well certain treatments will do in trials. Sometimes a trial surprises us and has results that are much, much better than anyone expected.
Maybe we'll get lucky and there really will be a blockbuster. It works on lots of patients, and economies of scale mean that it becomes cheaper because it is so popular. The investors win, the money savers win, and the patients win.
If that happens, I'll smarten up and start letting in advertisements. I'll need a little extra cash for investing.....
Thursday, January 28, 2016
Sunday, January 24, 2016
Narrowing Down Our Choices for Follicular Lymphoma Treatment?
Researchers from MD Anderson Cancer Center just published "Factors Influencing Outcome in Advanced Stage, Low-Grade Follicular Lymphoma Treated at MD Anderson Cancer Center in the Rituximab Era" in Annals of Oncology.
The title was a little misleading to me -- the focus isn't on a whole lot of factors other than certain treatments that patients received, although their conclusions do get into some wider issues.
Still, what they have to say is definitely worth taking a look at.
The researchers looked at patients from their facility only -- 356 of them who received certain treatments from 2004-2014 (a few years after Rituxan was introduced). As they point out (and as we all know), there really isn't an accepted first treatment for FL patients -- lots of disagreement about what to do first. So they hoped to look back at patients and see what treatment they received and how well they did, and figure out what seemed to work best. Thet used 3 year Progression-Free Survival as their measurement (that is, the disease didn't get any worse for at least 3 years).
Here is what they found:
For patients receiving R-CHOP, the 3 year PFS was 60%.
For patients receiving R-CHOP with Rituxan Maintenance, the 3 year PFS was 72%.
For patients receiving Bendamustine + R, the 3 year PFS was 63%.
For patients receiving Bendamustine + R with Rituxan Maintenance, the 3 year PFS was 97%.
For patients receiving Lenalidomide + Rituxan [R-squared], the 3 year PFS was 87%
While Bendamustine + R had the best number, the researchers also point out that R-squared had a very high number AND fewer "high risk features" than chemotherapy (which includes Bendamustine). We're seeing some very positive stuff about R-squared in the last few months, and this adds to it.
The researchers also looked at Overall Survival, and found that patients who had disease progression within two years after treatment had a lower OS (something we have been hearing more of in the last few months, too), and patients who transform have a lower OS (which we already knew).
Personally, I find the B + R + Maintenance number pretty impressive, but that R-squared statistic is also something that we can be happy about. The general trend seems to be moving away from chemotherapies, even one like Bendamustine that had fewer and less aggressive side effects than CHOP. R-squared, like other targeted therapies, are really what Follicular Lymphoma's future looks like.
As always, we need to think about all of this carefully -- it's a relatively small study, of patients in just one center, so other factors can also play a part in the results. But if we think about it all as part of some larger trends, this is all something to be happy about.
The title was a little misleading to me -- the focus isn't on a whole lot of factors other than certain treatments that patients received, although their conclusions do get into some wider issues.
Still, what they have to say is definitely worth taking a look at.
The researchers looked at patients from their facility only -- 356 of them who received certain treatments from 2004-2014 (a few years after Rituxan was introduced). As they point out (and as we all know), there really isn't an accepted first treatment for FL patients -- lots of disagreement about what to do first. So they hoped to look back at patients and see what treatment they received and how well they did, and figure out what seemed to work best. Thet used 3 year Progression-Free Survival as their measurement (that is, the disease didn't get any worse for at least 3 years).
Here is what they found:
For patients receiving R-CHOP, the 3 year PFS was 60%.
For patients receiving R-CHOP with Rituxan Maintenance, the 3 year PFS was 72%.
For patients receiving Bendamustine + R, the 3 year PFS was 63%.
For patients receiving Bendamustine + R with Rituxan Maintenance, the 3 year PFS was 97%.
For patients receiving Lenalidomide + Rituxan [R-squared], the 3 year PFS was 87%
While Bendamustine + R had the best number, the researchers also point out that R-squared had a very high number AND fewer "high risk features" than chemotherapy (which includes Bendamustine). We're seeing some very positive stuff about R-squared in the last few months, and this adds to it.
The researchers also looked at Overall Survival, and found that patients who had disease progression within two years after treatment had a lower OS (something we have been hearing more of in the last few months, too), and patients who transform have a lower OS (which we already knew).
Personally, I find the B + R + Maintenance number pretty impressive, but that R-squared statistic is also something that we can be happy about. The general trend seems to be moving away from chemotherapies, even one like Bendamustine that had fewer and less aggressive side effects than CHOP. R-squared, like other targeted therapies, are really what Follicular Lymphoma's future looks like.
As always, we need to think about all of this carefully -- it's a relatively small study, of patients in just one center, so other factors can also play a part in the results. But if we think about it all as part of some larger trends, this is all something to be happy about.
Tuesday, January 19, 2016
Emerging Agents for Follicular Lymphoma
OncLive has a brief interview with Dr. John Leonard of Weill Cornell, in which the good doctor discusses some of the more recent and upcoming treatments for Follicular Lymphoma.
As I said, this is a brief interview, but it's got some good stuff in it.
He mentions Ibrutinib and Idelalisib, but a lot of his focus is on Lenalidomide (also known as Revlimid), probably because he was lead author on an article from the Journal of Clinical Oncology from November, which I somehow missed.
(Before I get to that article, let me just swoon for a moment over some of Dr. Leonard's co-authors, which include Dr. Bruce Cheson, Dr. Myron Czuczma, and Dr. Nancy L. Bartlett, all Lymphoma Rock Stars. It's enough to make a cancer nerd's heart go all aflutter.)
The JOC article, called "Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)," described a study of 91 patients. Half of them received Lenalidomide, and half received Lenalidomide + Rituxan (also known as R-Squared). Those who had only Lenalidomide had a response rate of 53%, with 20% achieving a Complete Response, while the R-Squared patients had response rate of 76%, with 39% achieving a Complete Response. Also, the Lenalidomide patients had a 22% failure rate, meaning that many had to drop out of the treatment because of adverse events. the R-Squared patients also had a better median time to progression (how long it took for the FL to get worse) -- 2 years for R-Squared vs. 1.1 years for Lenalidomide. Clearly, adding Rituxan changes things for the better.
He also mentions the AUGMENT trial, which looks at R-Squared vs. straight Rituxan, which should give another perspective on how well that combination works.
Dr. Leonard also mentions Venetoclax a couple of times. I have heard of this, but haven't seen too much about it as it is used for Follicular Lymphoma. (I know it has been used effectively on Chronic Lymphocytic Leukemia, like so many other cool treatments.) Venetoclax is another pathway treatment, cutting off a process that a cancer cell needs to survive. In this case, Venetoclax targets bcl-2, a protein that keeps the cell alive. By shutting off bcl-2, Venetoclax basically gives the cell permission to die.
Venetoclax is in clinical trials for Follicular Lymphoma. From what I have read, it is pretty powerful stuff -- powerful enough that it needs to be very carefully monitored.(A patient died from tumor lysis after being on Venetoclax. This means that the contents of the dying cells changed the patient's blood chemistry too quickly. Close monitoring or lower doses might be possible changes that keep that from happening.)
So, for me, I learned a couple of new things from the brief interview -- updated data for R-Squared, and more about how Venetoclax might be useful for us in the future. Pretty good for such a quick read.
As I said, this is a brief interview, but it's got some good stuff in it.
He mentions Ibrutinib and Idelalisib, but a lot of his focus is on Lenalidomide (also known as Revlimid), probably because he was lead author on an article from the Journal of Clinical Oncology from November, which I somehow missed.
(Before I get to that article, let me just swoon for a moment over some of Dr. Leonard's co-authors, which include Dr. Bruce Cheson, Dr. Myron Czuczma, and Dr. Nancy L. Bartlett, all Lymphoma Rock Stars. It's enough to make a cancer nerd's heart go all aflutter.)
The JOC article, called "Randomized Trial of Lenalidomide Alone Versus Lenalidomide Plus Rituximab in Patients With Recurrent Follicular Lymphoma: CALGB 50401 (Alliance)," described a study of 91 patients. Half of them received Lenalidomide, and half received Lenalidomide + Rituxan (also known as R-Squared). Those who had only Lenalidomide had a response rate of 53%, with 20% achieving a Complete Response, while the R-Squared patients had response rate of 76%, with 39% achieving a Complete Response. Also, the Lenalidomide patients had a 22% failure rate, meaning that many had to drop out of the treatment because of adverse events. the R-Squared patients also had a better median time to progression (how long it took for the FL to get worse) -- 2 years for R-Squared vs. 1.1 years for Lenalidomide. Clearly, adding Rituxan changes things for the better.
He also mentions the AUGMENT trial, which looks at R-Squared vs. straight Rituxan, which should give another perspective on how well that combination works.
Dr. Leonard also mentions Venetoclax a couple of times. I have heard of this, but haven't seen too much about it as it is used for Follicular Lymphoma. (I know it has been used effectively on Chronic Lymphocytic Leukemia, like so many other cool treatments.) Venetoclax is another pathway treatment, cutting off a process that a cancer cell needs to survive. In this case, Venetoclax targets bcl-2, a protein that keeps the cell alive. By shutting off bcl-2, Venetoclax basically gives the cell permission to die.
Venetoclax is in clinical trials for Follicular Lymphoma. From what I have read, it is pretty powerful stuff -- powerful enough that it needs to be very carefully monitored.(A patient died from tumor lysis after being on Venetoclax. This means that the contents of the dying cells changed the patient's blood chemistry too quickly. Close monitoring or lower doses might be possible changes that keep that from happening.)
So, for me, I learned a couple of new things from the brief interview -- updated data for R-Squared, and more about how Venetoclax might be useful for us in the future. Pretty good for such a quick read.
venetoclax
Friday, January 15, 2016
8 Years
Today is my 8th diagnosiversary.
Eight years ago today, I was diagnosed with Follicular Lymphoma.
Six years ago today, I had my first Rituxan treatment (and then five more rounds after that, and I haven't needed any since then).
***************************
Eight years isn't a good round number like 10, and I look forward to that 10th diagnosiversary. But 8 is pretty significant anyway.
I can remember all of the uncertainty I felt when I was first diagnosed. I knew nothing about Follicular Lymphoma. Not like now, when I know way more than I wish I had to know.
I remember the ups and downs of those first few months -- learning something that gave me hope, and then hearing something that made all hope fly away. It took a while for that to even out.
I remember the thing that happened that makes 8 years significant. I was having a good day, and someone I love sent an email to my wife, worried. The loved one had looked up Follicular Lymphoma online, and had read on the Wikipedia page that the median survival for Follicular Lymphoma was 8-10 years. I was 40 years old at the time, with three young kids. My loved one had reason to be worried, thinking I'd be gone in 8 years. And, in my fragile emotional state, that got me worried, too. I can still remember the dull pain in my gut.
I know better now. I have no idea what the future brings, of course. But I do know how to read a statement like "median survival is 8-10 years." I know that statistic has nothing to do with me, personally, and that I can (and plan to) live for a very long time.
I also know that 8-10 year survival was probably a very low number, even for 2008. Over the last 8 years, I've seen studies that have bumped that number up, little by little. I remember seeing one, early on, that said that figure was based on pre-Rituxan era statistics, and that it was more likely 12-15 years. And then I saw a study that said younger patients like me were more likely to survive 18-21 years. And then, more recently, I've seen numbers that suggest it might be pushing 30.
I've learned to just sit back let the great Follicular Lymphoma researchers keep doing their work. If I just let it go, they'll have me living to be 100 before all is said and done.
******************************
But I also know how dangerous it is, still, to read things online. Just for fun, I looked back again at the Wikipedia page for Follicular Lymphoma, and under "Prognosis," it still says, "Median survival is around 10 years, but the range is wide, from less than one year, to more than 20 years. Some patients may never need treatment. The overall survival rate at 5 years is 72-77%."
That's a little better than what it said 8 years ago, but only a little -- especially if you click on the little footnote number at the end of that sentence, that takes you to the source for that statistic. It actually takes you to a Medscape page from last March. Nice -- Medscape is a respected source. But even that respected source says, "Despite the fact that most follicular lymphomas are advanced at the time of diagnosis, the median survival of patients with follicular lymphomas is approximately 8-10 years, and many patients may not require treatment for prolonged periods of time."
Wait -- what? We're back to 8-10 years? Look at the source for that statistic, and it's from an article published in....2007.
Ugh.
That was even before I was diagnosed.
In terms of cancer research, that's like a thousand years.
It's no wonder people get scared. There's still so much misinformation out there, even in places that one would hope would be more reliable.
The blog has always been good for me. It forces me to keep up on what's going on in the world of Follicular Lymphoma. I don't want to rely on information that might be out of date or unreliable. And if the blog helps other people, too -- all the better.
I'm a lot less scared than I used to be. Time and knowledge help a lot.
*********************************
So today I celebrate.
I don't celebrate being told that I have cancer. I celebrate the 2,920 days I've been alive since then.
In the years right after I was diagnosed, I would celebrate by skipping work, bringing the kids to school, and then going back to bed with my wife. Then we'd see an early movie and violate the "no outside food" policy and sneak sandwiches in with us.
Nothing quite so exciting planned for today. My wife and I went to the gym this morning, and we'll go out to dinner tonight. And then we'll come home for dessert, because my daughter, the award-winning baker and cake decorator, is making cupcakes that look like White Blood Cells.
(It's nice to know I have passed along my sense of humor to my kids, even if my wife thinks White Blood Cell cupcakes are "weird as hell." I'll post a picture after my daughter has decorated them.)
Edit: Here are the White Blood Cell cupcakes! Look for WBCs on Google Images -- these are very realistic. I love my cancer nerd children.
Thanks for reading, everybody.
And while I have seen plenty of doctors in the last 8 years, I'll let my favorite Doctor have the last word:
Eight years ago today, I was diagnosed with Follicular Lymphoma.
Six years ago today, I had my first Rituxan treatment (and then five more rounds after that, and I haven't needed any since then).
***************************
Eight years isn't a good round number like 10, and I look forward to that 10th diagnosiversary. But 8 is pretty significant anyway.
I can remember all of the uncertainty I felt when I was first diagnosed. I knew nothing about Follicular Lymphoma. Not like now, when I know way more than I wish I had to know.
I remember the ups and downs of those first few months -- learning something that gave me hope, and then hearing something that made all hope fly away. It took a while for that to even out.
I remember the thing that happened that makes 8 years significant. I was having a good day, and someone I love sent an email to my wife, worried. The loved one had looked up Follicular Lymphoma online, and had read on the Wikipedia page that the median survival for Follicular Lymphoma was 8-10 years. I was 40 years old at the time, with three young kids. My loved one had reason to be worried, thinking I'd be gone in 8 years. And, in my fragile emotional state, that got me worried, too. I can still remember the dull pain in my gut.
I know better now. I have no idea what the future brings, of course. But I do know how to read a statement like "median survival is 8-10 years." I know that statistic has nothing to do with me, personally, and that I can (and plan to) live for a very long time.
I also know that 8-10 year survival was probably a very low number, even for 2008. Over the last 8 years, I've seen studies that have bumped that number up, little by little. I remember seeing one, early on, that said that figure was based on pre-Rituxan era statistics, and that it was more likely 12-15 years. And then I saw a study that said younger patients like me were more likely to survive 18-21 years. And then, more recently, I've seen numbers that suggest it might be pushing 30.
I've learned to just sit back let the great Follicular Lymphoma researchers keep doing their work. If I just let it go, they'll have me living to be 100 before all is said and done.
******************************
But I also know how dangerous it is, still, to read things online. Just for fun, I looked back again at the Wikipedia page for Follicular Lymphoma, and under "Prognosis," it still says, "Median survival is around 10 years, but the range is wide, from less than one year, to more than 20 years. Some patients may never need treatment. The overall survival rate at 5 years is 72-77%."
That's a little better than what it said 8 years ago, but only a little -- especially if you click on the little footnote number at the end of that sentence, that takes you to the source for that statistic. It actually takes you to a Medscape page from last March. Nice -- Medscape is a respected source. But even that respected source says, "Despite the fact that most follicular lymphomas are advanced at the time of diagnosis, the median survival of patients with follicular lymphomas is approximately 8-10 years, and many patients may not require treatment for prolonged periods of time."
Wait -- what? We're back to 8-10 years? Look at the source for that statistic, and it's from an article published in....2007.
Ugh.
That was even before I was diagnosed.
In terms of cancer research, that's like a thousand years.
It's no wonder people get scared. There's still so much misinformation out there, even in places that one would hope would be more reliable.
The blog has always been good for me. It forces me to keep up on what's going on in the world of Follicular Lymphoma. I don't want to rely on information that might be out of date or unreliable. And if the blog helps other people, too -- all the better.
I'm a lot less scared than I used to be. Time and knowledge help a lot.
*********************************
So today I celebrate.
I don't celebrate being told that I have cancer. I celebrate the 2,920 days I've been alive since then.
In the years right after I was diagnosed, I would celebrate by skipping work, bringing the kids to school, and then going back to bed with my wife. Then we'd see an early movie and violate the "no outside food" policy and sneak sandwiches in with us.
Nothing quite so exciting planned for today. My wife and I went to the gym this morning, and we'll go out to dinner tonight. And then we'll come home for dessert, because my daughter, the award-winning baker and cake decorator, is making cupcakes that look like White Blood Cells.
(It's nice to know I have passed along my sense of humor to my kids, even if my wife thinks White Blood Cell cupcakes are "weird as hell." I'll post a picture after my daughter has decorated them.)
Edit: Here are the White Blood Cell cupcakes! Look for WBCs on Google Images -- these are very realistic. I love my cancer nerd children.
Thanks for reading, everybody.
And while I have seen plenty of doctors in the last 8 years, I'll let my favorite Doctor have the last word:
Tuesday, January 12, 2016
mTOR and Follicular Lymphoma
New research from Nature Genetics: "Recurrent mTORC1-activating RRAGC Mutations in Follicular Lymphoma."
Genetics is not my field, so it always takes extra effort for me to understand the research in a journal like this, but I'm going to do my best.
Cancer researchers have been focused for a while on "pathways." We know that chemotherapy works by killing off whole cancer cells (plus a bunch of non-cancer cells), and sometimes that works and sometimes it doesn't. As we have learned more about cancer, we have discovered that cells depend on "pathways" to grow and survive -- proteins or enzymes in the cell send signals that turn on switches that allow a bunch of different things to happen. These are "pathways" -- expected paths or steps that the cells need to take to do their jobs.
Cancer researchers have been targeting these pathways. If you can cut off a path or keep a step from happening, then the cell dies. Genetic research looks at the gene mutations that cause problems with these pathways. So in a normal cell, a certain gene allows the pathway that tells the cell to stop growing. But in a cancer cell, a gene might mutate or change in a way that the pathway is shut off, so the cell never gets the signal to stop growing.
And sometimes cancer cells have several mutations working at the same time, so several different pathways are affected.
The researchers who wrote this article are focused on the relationship between RRAGC, a certain gene, and the mTOR pathway. They found that with this particular mutation, the cell can become "resistant to amino acid deprivation." Basically, this pathway is supposed to turn on when it gets the signal that there is enough food for the cell to do its job. But because of the mutation, the cell does its job (dividing and growing) whether there is food or not. You can't starve this type of cancer -- it will grow anyway
The researchers estimate that about 30% of FL patients are affected by this mutation. While this particular mutation is a new discovery, the mTOR pathway has been known for a while, and it is already thought to be connected to several types of cancer, plus autism, Alzheimer's disease, and some other age-related problems. The researchers speculate that some of the mTOR pathway inhibitors currently in use could be effective against Follicular Lymphoma. Or, now that there is a new target, a new inhibitor could be developed.
So this research isn't going to lead to another arrow in the quiver anytime soon, but it is important because it gives us one more small piece of a very large and difficult puzzle. There are lots more pieces to be found, but it's nice to know this one is off the list.
Genetics is not my field, so it always takes extra effort for me to understand the research in a journal like this, but I'm going to do my best.
Cancer researchers have been focused for a while on "pathways." We know that chemotherapy works by killing off whole cancer cells (plus a bunch of non-cancer cells), and sometimes that works and sometimes it doesn't. As we have learned more about cancer, we have discovered that cells depend on "pathways" to grow and survive -- proteins or enzymes in the cell send signals that turn on switches that allow a bunch of different things to happen. These are "pathways" -- expected paths or steps that the cells need to take to do their jobs.
Cancer researchers have been targeting these pathways. If you can cut off a path or keep a step from happening, then the cell dies. Genetic research looks at the gene mutations that cause problems with these pathways. So in a normal cell, a certain gene allows the pathway that tells the cell to stop growing. But in a cancer cell, a gene might mutate or change in a way that the pathway is shut off, so the cell never gets the signal to stop growing.
And sometimes cancer cells have several mutations working at the same time, so several different pathways are affected.
The researchers who wrote this article are focused on the relationship between RRAGC, a certain gene, and the mTOR pathway. They found that with this particular mutation, the cell can become "resistant to amino acid deprivation." Basically, this pathway is supposed to turn on when it gets the signal that there is enough food for the cell to do its job. But because of the mutation, the cell does its job (dividing and growing) whether there is food or not. You can't starve this type of cancer -- it will grow anyway
The researchers estimate that about 30% of FL patients are affected by this mutation. While this particular mutation is a new discovery, the mTOR pathway has been known for a while, and it is already thought to be connected to several types of cancer, plus autism, Alzheimer's disease, and some other age-related problems. The researchers speculate that some of the mTOR pathway inhibitors currently in use could be effective against Follicular Lymphoma. Or, now that there is a new target, a new inhibitor could be developed.
So this research isn't going to lead to another arrow in the quiver anytime soon, but it is important because it gives us one more small piece of a very large and difficult puzzle. There are lots more pieces to be found, but it's nice to know this one is off the list.
Saturday, January 9, 2016
Patient Power: Beyond Chemotherapy
The good folks at Patient Power have a couple of videos that follow up on this year's ASH conference. One of them is an interview with Dr. Jennifer Cultrera, who discusses treatments for Follicular Lymphoma that move us beyond chemotherapy. If you've been keeping up with FL research, you know it's no surprise that specialists are looking beyond chemo.
The interview is available on Patient Power, but you need to be a member of their community to view it. If you aren't interesting in joining (it's free), Lymphoma News Today has also posted the interview.
Dr. Cultrera mentions immunotherapy and targeted treatments, which are getting lots of attention these days in cancer circles (not just Follicular Lymphoma circles). She makes the point that combined therapies are becoming more important (since someone's FL might be the result of a few different mutations), but they are also easier to combine, since the side effects aren't as bad as with traditional chemo. She thinks there will be "an explosion" of new treatments in the years to come.
However, Dr. Cultrera also discusses the importance of clinical trials, not only because they are a source of cutting-edge treatment. But more importantly, clinical trials need patients who are willing to try out the treatments, or they will never make it to the oncologist's office to help anybody. We can't expect an explosion of new treatments if there is no one to check them out.
(If you want to know more about clinical trials, including how to talk to your doctor about them, take a look at Lymphomation's "Focus on Clinical Trials.")
One final thought from Dr. Cultrera: she says she is a science fiction fan, and she remembers reading Arthur C. Clark predicting that in the year 3001, cancer patients would be able to take a pill every day to keep their cancer in check. That may happen in our lifetimes. There are pills out there that doing just that for a lot of people right now.
So this interview isn't a summary of what happened at ASH, but it does have some expert commentary on some of the general trends that people saw at the conference. Not a bad way to spend 7 minutes.
The interview is available on Patient Power, but you need to be a member of their community to view it. If you aren't interesting in joining (it's free), Lymphoma News Today has also posted the interview.
Dr. Cultrera mentions immunotherapy and targeted treatments, which are getting lots of attention these days in cancer circles (not just Follicular Lymphoma circles). She makes the point that combined therapies are becoming more important (since someone's FL might be the result of a few different mutations), but they are also easier to combine, since the side effects aren't as bad as with traditional chemo. She thinks there will be "an explosion" of new treatments in the years to come.
However, Dr. Cultrera also discusses the importance of clinical trials, not only because they are a source of cutting-edge treatment. But more importantly, clinical trials need patients who are willing to try out the treatments, or they will never make it to the oncologist's office to help anybody. We can't expect an explosion of new treatments if there is no one to check them out.
(If you want to know more about clinical trials, including how to talk to your doctor about them, take a look at Lymphomation's "Focus on Clinical Trials.")
One final thought from Dr. Cultrera: she says she is a science fiction fan, and she remembers reading Arthur C. Clark predicting that in the year 3001, cancer patients would be able to take a pill every day to keep their cancer in check. That may happen in our lifetimes. There are pills out there that doing just that for a lot of people right now.
So this interview isn't a summary of what happened at ASH, but it does have some expert commentary on some of the general trends that people saw at the conference. Not a bad way to spend 7 minutes.
Tuesday, January 5, 2016
Dr. Leonard's Top 10: m7-FLIPI
Lymphoma Rock Star Dr. John Leonard (of Weill Cornell Medical College) recently posted his Top 10 Lymphoma Abstracts from the ASH conference. Only one Follicular Lymphoma abstract made the list, and it wasn't one that caught my eye, so I'm adding it here.
In the Oncology Times article, Dr. Leonard says he looks for abstracts that are less focused on biology, and more on clinical practice -- not so much about new genetic discoveries, but more on how to treat patients now (or in the next few years). He also wants to start some conversation about which ASH abstracts are most important -- a goal that I certainly agree with.
Since he's looking at all of lymphoma, he has a lot to work with. If you have been following ASH and ASCO and other cancer meetings for the last few years, you know that CLL has been getting a lot of great stuff lately. And it seems like Hodgkin's Lymphoma and DLBCL have also been getting a lot of attention. There have been good things happening with Follicular Lymphoma, too, but not quite as many, or quite as exciting, as some other types of blood cancer.
And so, Dr. Leonard only includes one abstract that deals directly with FL. It's this one: "A Clinicogenetic Risk Model (m7-FLIPI) Prospectively Identifies One-Half of Patients with Early Disease Progression of Follicular Lymphoma after First-Line Immunochemotherapy."Interestingly, it isn't one that caught my eye as I was looking at abstracts to discuss. I think I overlooked it because the subject of the abstract (developing the m7-FLIPI scale) came up over the summer, so I didn't think there would be anything new presented at ASH.
But there was some new stuff, so I'm glad Dr. Leonard pointed it out. The ASH presentation doesn't focus on how the developed the m7-FLIPI model, but more on how it can be used to identify high-risk FL patients before they received treatment.
A quick review on FLIPI, the Follicular Lymphoma International Prognostic Index. FLIPI is often used to categorize patients for clinical trials by giving a general sense of whether they are low risk or high risk. It is sometimes used to help a doctor determine whether or not to use an aggressive or less aggressive form of treatment on a patient, but FLIPI is not really the best way of doing that, because the factors are very general (things like age and stage) that don't necessarily determine how a patient's FL is going to behave. (For more on FLIPI and FLIPI-2, a revised version on FLIPI, I suggest visiting Lymphomation's discussion of the topic.)
One of the things that makes m7-FLIPI much better at being used as a tool for individual patients is that added "m7" part. That stands for the "Mutated Seven," which would be an excellent name for a team of Marvel super heroes, but really stands for seven genes that affect Follicular Lymphoma when they become mutated. The m7-FLIPI takes those mutations into account, which makes it much more specific to the individual patient than the old FLIPI.
The ASH abstract that was flagged by Dr. Leonard involved looking at patients who were potentially high-risk. Recent research has shown that patients who had chemo and then relapsed within 2 years might actually be part of a subset of FL patients that need to be treated differently. The researchers here are hoping that the m7-FLIPI would help identify those patients early on -- not two years down the road when things have progressed.
In the end, the m7-FLIPI did a decent job, but not a perfect job, and the researchers conclude that the index needs to be refined even more. The abstract tells us something about FLIPI indexes, no matter which one gets used -- they aren't perfect in identifying how an individual patient's FL is going to behave. There's nothing new there. We've always been mystified by this disease. There's still no accurate way to tell if we have a less aggressive version, or if it might transform, or anything else. It's all still a crap shoot.
Still, the study gives us some reason to hope. In Dr. Leonard's words:
In the Oncology Times article, Dr. Leonard says he looks for abstracts that are less focused on biology, and more on clinical practice -- not so much about new genetic discoveries, but more on how to treat patients now (or in the next few years). He also wants to start some conversation about which ASH abstracts are most important -- a goal that I certainly agree with.
Since he's looking at all of lymphoma, he has a lot to work with. If you have been following ASH and ASCO and other cancer meetings for the last few years, you know that CLL has been getting a lot of great stuff lately. And it seems like Hodgkin's Lymphoma and DLBCL have also been getting a lot of attention. There have been good things happening with Follicular Lymphoma, too, but not quite as many, or quite as exciting, as some other types of blood cancer.
And so, Dr. Leonard only includes one abstract that deals directly with FL. It's this one: "A Clinicogenetic Risk Model (m7-FLIPI) Prospectively Identifies One-Half of Patients with Early Disease Progression of Follicular Lymphoma after First-Line Immunochemotherapy."Interestingly, it isn't one that caught my eye as I was looking at abstracts to discuss. I think I overlooked it because the subject of the abstract (developing the m7-FLIPI scale) came up over the summer, so I didn't think there would be anything new presented at ASH.
But there was some new stuff, so I'm glad Dr. Leonard pointed it out. The ASH presentation doesn't focus on how the developed the m7-FLIPI model, but more on how it can be used to identify high-risk FL patients before they received treatment.
A quick review on FLIPI, the Follicular Lymphoma International Prognostic Index. FLIPI is often used to categorize patients for clinical trials by giving a general sense of whether they are low risk or high risk. It is sometimes used to help a doctor determine whether or not to use an aggressive or less aggressive form of treatment on a patient, but FLIPI is not really the best way of doing that, because the factors are very general (things like age and stage) that don't necessarily determine how a patient's FL is going to behave. (For more on FLIPI and FLIPI-2, a revised version on FLIPI, I suggest visiting Lymphomation's discussion of the topic.)
One of the things that makes m7-FLIPI much better at being used as a tool for individual patients is that added "m7" part. That stands for the "Mutated Seven," which would be an excellent name for a team of Marvel super heroes, but really stands for seven genes that affect Follicular Lymphoma when they become mutated. The m7-FLIPI takes those mutations into account, which makes it much more specific to the individual patient than the old FLIPI.
The ASH abstract that was flagged by Dr. Leonard involved looking at patients who were potentially high-risk. Recent research has shown that patients who had chemo and then relapsed within 2 years might actually be part of a subset of FL patients that need to be treated differently. The researchers here are hoping that the m7-FLIPI would help identify those patients early on -- not two years down the road when things have progressed.
In the end, the m7-FLIPI did a decent job, but not a perfect job, and the researchers conclude that the index needs to be refined even more. The abstract tells us something about FLIPI indexes, no matter which one gets used -- they aren't perfect in identifying how an individual patient's FL is going to behave. There's nothing new there. We've always been mystified by this disease. There's still no accurate way to tell if we have a less aggressive version, or if it might transform, or anything else. It's all still a crap shoot.
Still, the study gives us some reason to hope. In Dr. Leonard's words:
“We know that patients with follicular lymphoma who have
progressed within two years of their front-line therapy have an
unfavorable prognosis long term, whereas those who progress late than
two years have a much more favorable prognosis.
“The question is, how can we identify these patients
earlier and, potentially through clinical trials and hopefully in
clinical practice, treat them differently?
“Using the m-7 FLIPI prognostic score plus some
molecular markers may identify a group of patients who will progress
relatively early after front-line immunochemotherapy. Identifying them
in advance of treating them and waiting to see what happens is a
positive step in that direction.”
And we all know that even a small positive step is a good thing.