The Motley Fool investing website has another lymphoma-related article up. This one talks about investment opportunities in companies that create and market monoclonal antibodies.
Of course, the lymphoma connection comes in the discussion about Roche, owner of My Old Pal Rituxan. Apparently, Rituxan generates about $7 billion in sales every year, more than Roche's other big MABs, Avastin, which discourages blood vessel growth in solid cancers, and Herceptin, which has made such a difference for so many breast cancer patients.
A couple of thoughts on this:
First, I found it kind of amazing that Rituxan sales were so high. But I guess it makes sense. Rituxan is used in a bunch of B cell Lymophomas, not just Follicular Lymphoma, but also some leukemias, as well as autoimmune diseases like Rheumatoid Arthritis, MS, and Lupus. Pretty impressive little MAB there.
That also gets me thinking about difficult it has been to find another MAB that trumps Rituxan. There really isn't anything approved yet that shows huge gains over Rituxan in terms of effectiveness. At some point, I have to wonder if we've plateaued on MABs for Follicular Lymphoma, and maybe we need to turn our attention elsewhere. (When I say "our," of course, I mean "researchers." We're all in this together.)
That said, there are still a ton of MABs for Follicular Lymphoma (and other blood cancers) in various stages of development, and it will take years before they are fully developed and explored in combination with other treatments, so I don't want to jump the gun.
Finally, I still have mixed feelings about people profiting off of my cancer, but I know I need to get over that. Treatments take many years and millions of dollars to develop, so there needs to be some incentive for people to pony up the money to make that happen. A friend of mine, a liver cancer survivor, told me he made a bundle on a treatment that was in trial. He was rejected for the trial, which upset him, because he was sure the treatment was going to take off. So he invested in the company anyway, and early trial results gave him a nice profit -- and some satisfaction.
So I hope other MABs, and other Follicular Lymphoma treatments, make someone a ton of money. That can only mean they're working.
Friday, August 30, 2013
Wednesday, August 28, 2013
Cancer Awareness for Men
The Lehigh Valley Iron Pigs, a minor league baseball team from Pennsylvania, hosted a Prostate Cancer Awareness Night last night. Players and coaches wore special uniforms, and there was a raffle to benefit The Prostate Cancer Awareness Fund of the Lehigh Valley.
But the highlight had to be the "foam finger" giveaway. The first 3500 fans 18 and older received one, courtesy of the Urology Specialists of the Lehigh Valley.
I'm going to just withhold any other comment, other than to say I'm all for anything that encourages people to get any kind of cancer screening (and yes, Urology Specialists will be offering a free health assessment, including a PSA test and digital exam), and I generally love any attempts at cancer humor.
But the highlight had to be the "foam finger" giveaway. The first 3500 fans 18 and older received one, courtesy of the Urology Specialists of the Lehigh Valley.
I'm going to just withhold any other comment, other than to say I'm all for anything that encourages people to get any kind of cancer screening (and yes, Urology Specialists will be offering a free health assessment, including a PSA test and digital exam), and I generally love any attempts at cancer humor.
Monday, August 26, 2013
Rituxan Maintenance for Follicular Lymphoma
The soon-to-be-published next issue of the Journal of Clinical Oncology has another significant article coming out, this one reporting the results of a phase III trial looking at Rituxan maintenance in a specific population. It raises some interesting questions about the effectiveness of R maintenance -- more on that in a little bit.
The study focused on Follicular Lymphoma patients over 60 who had not received treatment. The researchers had two overarching goals -- the same goals that most researchers of FL treatments have: First, how can we find an effective treatment with less toxicity? Second, can we make the good results last longer than other treatments?
Their solution was to try a shorter course of R-FND (Rituxan, Fludarabine, Mitoxantrone, and Dexamethason), a not-uncommon treatment for older patients. (Fludarabine is fairly effective, but might get in the way of collecting stem cells later on, and can cause some secondary blood cancers years down the road -- less of a risk for older patients.) The patients received four monthly R-FND treatments, a less intense course than is typically given. These were followed up by a consolidation therapy (a second, different treatment given immediately after the first one, meant to catch any cancery leftovers): four weekly rounds of Rituxan.
This part of the study was fairly successful. Overall response was 86%, with 69% having a complete response. This answers that first question (how can we find an effective treatment with less toxicity?) with a big Yes.
Then came the second part of the study. The patients who remained in the study were divided into two groups: half were given Rituxan Maintenance (4 rounds, given every two months) and the other half were observed with no additional treatment. So, the answer to the second question (can we make the good results last longer than other treatments?) was a no. While the R-maintenance group had a 2-year Progression Free Survival of 81%, and the observation group's was 69%, this was not considered statistically significant (that is, there wasn't a big enough difference to say for sure that it was the Rituxan and not some other random factor).
On the surface, this would seem to be a blow for Rituxan maintenance. There was, after all, no real difference between the two groups.
However, two wicked smaht people from Dana-Farber in Boston wrote an accompanying editorial on the study called "One Size Does Not Fit All in Follicular Lymphoma." In their analysis of the study, R-maintenance isn't necessarily ineffective for FL. They point out that this is one of the few that does not show a benefit for R-maintenance. Another study, for example, tried R-maintenance with three groups -- some receiving R-CHOP, some R-CVP, and some R+another Fludarabine combo. The one that didn't get a maintenance benefit? The Fludarabine group. Their conclusion? Maybe R-maintenance doesn't work with some initial treatments (*cough-Fludarabine-cough*). They also point out that, given how effective Bendamustine is, with its much lower toxicity, maybe we just shouldn't bother with Fludarabine? Their final word: let's not assume Rituxan maintenance with work on everyone with Follicular Lymphoma; let's figure out which treatments it works best with first, and then use it with them.
I don't have much to add; the good folks from Boston did a fine job with their analysis. (Because, you know, they are cancer researchers at Dana-Farber, as opposed to me, who isn't.)
But it does provide some excellent food for thought when treatment decisions have to be made.
The study focused on Follicular Lymphoma patients over 60 who had not received treatment. The researchers had two overarching goals -- the same goals that most researchers of FL treatments have: First, how can we find an effective treatment with less toxicity? Second, can we make the good results last longer than other treatments?
Their solution was to try a shorter course of R-FND (Rituxan, Fludarabine, Mitoxantrone, and Dexamethason), a not-uncommon treatment for older patients. (Fludarabine is fairly effective, but might get in the way of collecting stem cells later on, and can cause some secondary blood cancers years down the road -- less of a risk for older patients.) The patients received four monthly R-FND treatments, a less intense course than is typically given. These were followed up by a consolidation therapy (a second, different treatment given immediately after the first one, meant to catch any cancery leftovers): four weekly rounds of Rituxan.
This part of the study was fairly successful. Overall response was 86%, with 69% having a complete response. This answers that first question (how can we find an effective treatment with less toxicity?) with a big Yes.
Then came the second part of the study. The patients who remained in the study were divided into two groups: half were given Rituxan Maintenance (4 rounds, given every two months) and the other half were observed with no additional treatment. So, the answer to the second question (can we make the good results last longer than other treatments?) was a no. While the R-maintenance group had a 2-year Progression Free Survival of 81%, and the observation group's was 69%, this was not considered statistically significant (that is, there wasn't a big enough difference to say for sure that it was the Rituxan and not some other random factor).
On the surface, this would seem to be a blow for Rituxan maintenance. There was, after all, no real difference between the two groups.
However, two wicked smaht people from Dana-Farber in Boston wrote an accompanying editorial on the study called "One Size Does Not Fit All in Follicular Lymphoma." In their analysis of the study, R-maintenance isn't necessarily ineffective for FL. They point out that this is one of the few that does not show a benefit for R-maintenance. Another study, for example, tried R-maintenance with three groups -- some receiving R-CHOP, some R-CVP, and some R+another Fludarabine combo. The one that didn't get a maintenance benefit? The Fludarabine group. Their conclusion? Maybe R-maintenance doesn't work with some initial treatments (*cough-Fludarabine-cough*). They also point out that, given how effective Bendamustine is, with its much lower toxicity, maybe we just shouldn't bother with Fludarabine? Their final word: let's not assume Rituxan maintenance with work on everyone with Follicular Lymphoma; let's figure out which treatments it works best with first, and then use it with them.
I don't have much to add; the good folks from Boston did a fine job with their analysis. (Because, you know, they are cancer researchers at Dana-Farber, as opposed to me, who isn't.)
But it does provide some excellent food for thought when treatment decisions have to be made.
Friday, August 23, 2013
Follicular Lymphoma: Obinutuzumab (GA101)
From the August 10 edition of The Journal of Clinical Oncology comes a report from France on dosing for Obinutuzumab (also known as GA101).
Not a hugely ground-breaking report (though it is part of a larger study): 40 Follicular Lymphoma patients were given Obinutuzumab, but in different doses. Half the patients received 400 mg of Obinutuzumab for 8 cycles; the other half received 1600 mg initially, and then 800 for the rest of the cycles. Results were clearly better for the 1600 group: 55% had a response, while only 17% of the 400 group responded.
That 55% doesn't seem all that impressive, but there are further results that make this a little better: 38 of the 40 patients had already had Rituxan, and 22 of them were refractory to Rituxan (meaning Rituxan had pretty much stopped working, which is not uncommon with Rituxan). Of the 10 patients who were refractory and had the 1600 mg, 5 had a response. Of the 12 in the 400 group, only 1 had a response.
I think this is significant. Obinutuzumab might be an option for people who tried Rituxan and had it fail. Both target CD20 on B cells, but apparently work by different mechanisms (so says the head of the study, Dr. Gilles Salles, in another article that reported on these results).
Now, as I was writng this, I couldn't help thinking about another very recent report on a Monoclonal Antibody seen as a rival to Rituxan -- Epratuzumab, which had very similar results to Rituxan, and which I was kind of negative about in a post last week. The two reports (on Epratuzumab and Obinutuzuma) are similar in a way, both offering alternatives to Rituxan, with presumably similar side effects. So why am I a little more excited about this report on Obinutuzumab, which doesn't seem as effective as Rituxan?
Let me clear: I'm not down on Epratuzumab by any means. I think it's a great thing, and another necessary arrow in the quiver. But I really objected to the way the manufacturer was "selling" it in the press release, as something people can try if they don't want chemo. I guess I don't like it's being presented as a choice, as if fear of losing hair is the only factor. It certainly is a factor -- I would never discount the emotional issues that go into choosing a treatment. If that's the only issue, there are other things to try -- including Rituxan. Why offer a choice when time could be spent on something better than what we have?
Obinutuzumab, as it is presented here, is not just a choice other than Rituxan. It's an option for when Rituxan fails. There is, to me, a big difference.
It's hard being a cancer patient. There are people who think having an indolent lymphoma is good ("If you're going to have one, this is the one to have," some of us have heard). We have more choices, and often more time to choose. We're lucky that way. But it has its downsides, too.
The bottom line is, as Follicular Lymphoma patients, we have three possible monoclonal antibodies to choose from -- Rituxan, Epratuzuma, and Obinutuzumab. They do different things, and they'll be appropriate in different situations. With our oncologists' help, we should be able to make the right choice.
Not a hugely ground-breaking report (though it is part of a larger study): 40 Follicular Lymphoma patients were given Obinutuzumab, but in different doses. Half the patients received 400 mg of Obinutuzumab for 8 cycles; the other half received 1600 mg initially, and then 800 for the rest of the cycles. Results were clearly better for the 1600 group: 55% had a response, while only 17% of the 400 group responded.
That 55% doesn't seem all that impressive, but there are further results that make this a little better: 38 of the 40 patients had already had Rituxan, and 22 of them were refractory to Rituxan (meaning Rituxan had pretty much stopped working, which is not uncommon with Rituxan). Of the 10 patients who were refractory and had the 1600 mg, 5 had a response. Of the 12 in the 400 group, only 1 had a response.
I think this is significant. Obinutuzumab might be an option for people who tried Rituxan and had it fail. Both target CD20 on B cells, but apparently work by different mechanisms (so says the head of the study, Dr. Gilles Salles, in another article that reported on these results).
Now, as I was writng this, I couldn't help thinking about another very recent report on a Monoclonal Antibody seen as a rival to Rituxan -- Epratuzumab, which had very similar results to Rituxan, and which I was kind of negative about in a post last week. The two reports (on Epratuzumab and Obinutuzuma) are similar in a way, both offering alternatives to Rituxan, with presumably similar side effects. So why am I a little more excited about this report on Obinutuzumab, which doesn't seem as effective as Rituxan?
Let me clear: I'm not down on Epratuzumab by any means. I think it's a great thing, and another necessary arrow in the quiver. But I really objected to the way the manufacturer was "selling" it in the press release, as something people can try if they don't want chemo. I guess I don't like it's being presented as a choice, as if fear of losing hair is the only factor. It certainly is a factor -- I would never discount the emotional issues that go into choosing a treatment. If that's the only issue, there are other things to try -- including Rituxan. Why offer a choice when time could be spent on something better than what we have?
Obinutuzumab, as it is presented here, is not just a choice other than Rituxan. It's an option for when Rituxan fails. There is, to me, a big difference.
It's hard being a cancer patient. There are people who think having an indolent lymphoma is good ("If you're going to have one, this is the one to have," some of us have heard). We have more choices, and often more time to choose. We're lucky that way. But it has its downsides, too.
The bottom line is, as Follicular Lymphoma patients, we have three possible monoclonal antibodies to choose from -- Rituxan, Epratuzuma, and Obinutuzumab. They do different things, and they'll be appropriate in different situations. With our oncologists' help, we should be able to make the right choice.
Wednesday, August 21, 2013
Stress (from Cancer and Other Things)
I saw this on a lymphoma group on Facebook this morning, though it's made the rounds for a few months (and it's usually cited as "source unknown," so I can't give proper credit):
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A psychologist walked around a room while teaching stress management to an audience. As she raised a glass of water, everyone expected they'd be asked the "half empty or half full" question. Instead, with a smile on her face, she inquired: "How heavy is this glass of water?"
Answers called out ranged from 8 oz. to 20 oz.
She replied, "The absolute weight doesn't matter. It depends on how long I hold it.
"If I hold it for a minute, it's not a problem. If I hold it for an hour, I'll have an ache in my arm. If I hold it for a day, my arm will feel numb and paralyzed. In each case, the weight of the glass doesn't change, but the longer I hold it, the heavier it becomes."
She continued, "The stresses and worries in life are like that glass of water. Think about them for a while and nothing happens. Think about them a bit longer and they begin to hurt. And if you think about them all day long, you will feel paralyzed – incapable of doing anything."
It’s important to remember to let go of your stresses. As early in the evening as you can, put all your burdens down. Don't carry them through the evening and into the night. Remember to put the glass down!
************************
I know that's easier said than done for lots of people -- maybe most people. But sometimes I think it's easy to worry about what might happen, rather than what it happening. There's a difference between preparing for what comes next and focusing on the worst possible outcome.
I've written many times before that, with a wife, three double-digit-aged kids, a full-time job, and an insane dog, I am a very busy man. And I consider myself very lucky to be so busy. I have all of those people and things to care about, and to care about me, and the good health to stay busy enjoying them.
I wish all of you the good health and busy-ness to not have time to stand around holding a glass of water.
(That story is aimed to two people in particular -- you probably know who you are....)
****************************
A psychologist walked around a room while teaching stress management to an audience. As she raised a glass of water, everyone expected they'd be asked the "half empty or half full" question. Instead, with a smile on her face, she inquired: "How heavy is this glass of water?"
Answers called out ranged from 8 oz. to 20 oz.
She replied, "The absolute weight doesn't matter. It depends on how long I hold it.
"If I hold it for a minute, it's not a problem. If I hold it for an hour, I'll have an ache in my arm. If I hold it for a day, my arm will feel numb and paralyzed. In each case, the weight of the glass doesn't change, but the longer I hold it, the heavier it becomes."
She continued, "The stresses and worries in life are like that glass of water. Think about them for a while and nothing happens. Think about them a bit longer and they begin to hurt. And if you think about them all day long, you will feel paralyzed – incapable of doing anything."
It’s important to remember to let go of your stresses. As early in the evening as you can, put all your burdens down. Don't carry them through the evening and into the night. Remember to put the glass down!
************************
I know that's easier said than done for lots of people -- maybe most people. But sometimes I think it's easy to worry about what might happen, rather than what it happening. There's a difference between preparing for what comes next and focusing on the worst possible outcome.
I've written many times before that, with a wife, three double-digit-aged kids, a full-time job, and an insane dog, I am a very busy man. And I consider myself very lucky to be so busy. I have all of those people and things to care about, and to care about me, and the good health to stay busy enjoying them.
I wish all of you the good health and busy-ness to not have time to stand around holding a glass of water.
(That story is aimed to two people in particular -- you probably know who you are....)
Sunday, August 18, 2013
Ibrutinib and R-CHOP
This is a little bit related to Follicular Lymphoma, but enough that it's probably worth mentioning.
An early-phase study of Ibrutinib combined with Rituxan and the CHOP chemotherapy had good results for patients with DLBCL. Only 15 patients in the study, but all of them had responses -- 10 complete and 5 partial. The study's primary aims were to determine optimal dosage for Ibrutinib and to determine side effects. The results were good enough to warrent larger trials with more patients.
I think this is important for Follicular Lymphoma patients for several reasons:
First, the results for those 15 patients came after an initial trial involving patients with otiher types of NHL, including Follicular Lymphoma. All of those patients had a response, which led to the second part, with just the DLBCL patients. So there is some (very small) indication that this combination could work well someday for Follicular patients.
This is not a surprise, of course. R-CHOP has long been a choice for FL patients, and Ibrutinib seems to be working for us, too. The question was whether or not they would interfere with each other. It seems like they don't.
That's the second (related) reason. There's a school of thought that traditional chemo isn't going away any time soon, and rather than looking for alternatives, we should be looking to enhance what we have, that we know is effective. This lends some support to that way of thinking. It's the same thinking that encourages RIT as a consolidation therapy -- getting Zevalin right after R-CHOP. You have three different ways of attacking the cancer cells: chemo + antibody + RIT. This approach does something similar: chemo + antibody + kinase inhibitor. There's something to be said for this way of thinking. Until we have one treatment that can handle the job, ganging up might be the way to go.
Finally, as much as we hate to think about it, I'm always interested in treatments that might be an improvement in how we deal with DLBCL, since this is the lymphoma that most Follicular Lymphomas transform into, if and when it does transform. It might not be the exact same disease -- transformed DLBCL might be a little different than "original" DLBCL, which is why they have separate trials for them -- but it's good to know there's another avenue for future exploration by researchers.
As always, the warning: 15 patients is a really small number, and this is a really early trial. But it's got some stuff in there that make it worth keeping an eye on.
An early-phase study of Ibrutinib combined with Rituxan and the CHOP chemotherapy had good results for patients with DLBCL. Only 15 patients in the study, but all of them had responses -- 10 complete and 5 partial. The study's primary aims were to determine optimal dosage for Ibrutinib and to determine side effects. The results were good enough to warrent larger trials with more patients.
I think this is important for Follicular Lymphoma patients for several reasons:
First, the results for those 15 patients came after an initial trial involving patients with otiher types of NHL, including Follicular Lymphoma. All of those patients had a response, which led to the second part, with just the DLBCL patients. So there is some (very small) indication that this combination could work well someday for Follicular patients.
This is not a surprise, of course. R-CHOP has long been a choice for FL patients, and Ibrutinib seems to be working for us, too. The question was whether or not they would interfere with each other. It seems like they don't.
That's the second (related) reason. There's a school of thought that traditional chemo isn't going away any time soon, and rather than looking for alternatives, we should be looking to enhance what we have, that we know is effective. This lends some support to that way of thinking. It's the same thinking that encourages RIT as a consolidation therapy -- getting Zevalin right after R-CHOP. You have three different ways of attacking the cancer cells: chemo + antibody + RIT. This approach does something similar: chemo + antibody + kinase inhibitor. There's something to be said for this way of thinking. Until we have one treatment that can handle the job, ganging up might be the way to go.
Finally, as much as we hate to think about it, I'm always interested in treatments that might be an improvement in how we deal with DLBCL, since this is the lymphoma that most Follicular Lymphomas transform into, if and when it does transform. It might not be the exact same disease -- transformed DLBCL might be a little different than "original" DLBCL, which is why they have separate trials for them -- but it's good to know there's another avenue for future exploration by researchers.
As always, the warning: 15 patients is a really small number, and this is a really early trial. But it's got some stuff in there that make it worth keeping an eye on.
Thursday, August 15, 2013
Follicular Lymphoma: Epratuzumab
This just in:
Press release yesterday afternoon from Immunomedics with the results of a phase II trial of Epratuzumab and Rituxin in previously untreated Follicular Lymphoma patients.
Dang good results: 59 patients, 88.2% achieved a response. The breakdown: 25 of them (42.4%) had a complete response, and 27 (45.8%) had a partial response. Another 6 (10.2%) kept things stable. After 3 years, 60% of patients are still in remission.
Not bad at all.
Epratuzumab, like Rituxan, is a monoclonal antibody (there's that -mab ending again). While Rituxan targets the CD20 protein on a cancer cell, Epratuzumab goes after the CD22 protein. This seems to be why they work well together: if one misses a cell's target, the other might be able to catch it. Another difference is that Epratuzumab is humanized, unlike Rituxan, which is made from mouse cells. So Epratuzumab is likely to result in fewer allergic reactions.
Now, the cold water:
First, it's a phase II trial. I'm guessing the results will hold up in a larger, phase III trial, but it's still a while before FDA approval.
Second. the press release points out that "Although rituximab combined with chemotherapy has improved the survival of previously untreated patients with FL, many patients are unable or unwilling to tolerate chemotherapy," and thus this combination might be an alternative. Interesting way of positioning itself. If this is meant for initial therapy (the patients were all previously untreated), it's hard to tell if anyone would be "unable...to tolerate chemotherapy" before they actually had any chemo. I suppose the potential patient could have tried a round or two and then had a rough time and dropped it, and so this is an alternative. As for those "unwilling to tolerate chemotherapy," I can't imagine they wouldn't try straight Rituxan first (though it sounds like they received both MABs at the same time for four weeks; still, why not try just one?).
So, I guess I'm confused about who would use this, given that statement. The results are great, no question. But not all that much better than Rituxan, which has, if I remember correctly, about 75% overall response, and about 50% complete response, with about 24 months of progression free survival. Every little improvement helps, though I wonder how an insurance company will evaluate the additional cost for a few months of PFS.
That's uncharacteristically negative of me. Maybe I'm just hoping we can move beyond antibodies for initial treatments and focus more on some newer combinations? (Jeepers -- am I getting all spoiled by kinase inhibitors? Losing my boyish enthusiasm for every new treatment? I hope not....)
OK, we'll call it good news. Epratuzumab is definitely another arrow in the quiver. But I want to see more.
Press release yesterday afternoon from Immunomedics with the results of a phase II trial of Epratuzumab and Rituxin in previously untreated Follicular Lymphoma patients.
Dang good results: 59 patients, 88.2% achieved a response. The breakdown: 25 of them (42.4%) had a complete response, and 27 (45.8%) had a partial response. Another 6 (10.2%) kept things stable. After 3 years, 60% of patients are still in remission.
Not bad at all.
Epratuzumab, like Rituxan, is a monoclonal antibody (there's that -mab ending again). While Rituxan targets the CD20 protein on a cancer cell, Epratuzumab goes after the CD22 protein. This seems to be why they work well together: if one misses a cell's target, the other might be able to catch it. Another difference is that Epratuzumab is humanized, unlike Rituxan, which is made from mouse cells. So Epratuzumab is likely to result in fewer allergic reactions.
Now, the cold water:
First, it's a phase II trial. I'm guessing the results will hold up in a larger, phase III trial, but it's still a while before FDA approval.
Second. the press release points out that "Although rituximab combined with chemotherapy has improved the survival of previously untreated patients with FL, many patients are unable or unwilling to tolerate chemotherapy," and thus this combination might be an alternative. Interesting way of positioning itself. If this is meant for initial therapy (the patients were all previously untreated), it's hard to tell if anyone would be "unable...to tolerate chemotherapy" before they actually had any chemo. I suppose the potential patient could have tried a round or two and then had a rough time and dropped it, and so this is an alternative. As for those "unwilling to tolerate chemotherapy," I can't imagine they wouldn't try straight Rituxan first (though it sounds like they received both MABs at the same time for four weeks; still, why not try just one?).
So, I guess I'm confused about who would use this, given that statement. The results are great, no question. But not all that much better than Rituxan, which has, if I remember correctly, about 75% overall response, and about 50% complete response, with about 24 months of progression free survival. Every little improvement helps, though I wonder how an insurance company will evaluate the additional cost for a few months of PFS.
That's uncharacteristically negative of me. Maybe I'm just hoping we can move beyond antibodies for initial treatments and focus more on some newer combinations? (Jeepers -- am I getting all spoiled by kinase inhibitors? Losing my boyish enthusiasm for every new treatment? I hope not....)
OK, we'll call it good news. Epratuzumab is definitely another arrow in the quiver. But I want to see more.
Tuesday, August 13, 2013
Follicular Lymphoma Microenvironment
Interesting (though very early) research on Follicular Lymphoma's microenvironment from the July issue of the Journal of Clinical Oncology, and an article from British researchers called "Follicular Lymphoma Cells Induce Changes in T-Cell Gene Expression and Function: Potential Impact on Survival and Risk of Transformation."
As the title implies, the article describes how Follicular Lymphoma cells mess with the body's defenses, and furthermore, how looking closely as those messes might (might) tell us something about the likelihood of a patient's survival and/or transformation to an aggressive lymphoma.
The researchers knew (as we all do) that cancer cells do a fantastic job of tricking the body's natural defenses into thinking that everything is OK, allowing the cancer cells to grow unchecked. Normally, an invader or a threatening cell is destroyed by an immune system cell, either a B cell or a T cell. These reserchers looked specifically at a kind of T cell called a TIL (Tumor-Infiltrating T Cell), which is a T cell that leaves the bloodstream (where they hang out an wait) and attaches itself to a tumor. They took TIL samples from biopsies from 172 Follicular Lymphoma patients before they had treatment, and compared them to healthy T cells from 12 people who were lucky enough to not have cancer. They found that the TILs had several genetic changes, compared to the healthy T cells.
Then they went a step further, and exposed the healthy T cells to Follicular Lymphoma cells, and found that the cells changed in the same way. So, clearly, the Follicular Lymphoma cells have something to do with the genetic changes. In addition to messing with their genes (and making them less effective), the healthy cells also had decreased mobility, so they couldn't move to their target as easily as healthy T cells.
One last step: they looked at how many TILs were present, and where they showed up, and found that that number and location had a serious correlation to overall survival and the chances for transformation.
BUT -- the researchers are very careful to talk about the implications. Right now, there aren't any. It's just too early. The results help us understand just how complex the microenvironment is, and might give us some new clues about what's going on in there. But there will need to be a whole lot more done before we can figure out how this is going to lead to any treatments. For that matter, it will still be a while before we even know how all of this will help predict whether or not a patient will transform.
So, as I said, interesting, but very early research.
I see it as another small piece of a 10,000 piece puzzle being put into place. Once we get the edges done, we can start to work our way in, and at some point, it all comes together.
Until then, patience and hope.
As the title implies, the article describes how Follicular Lymphoma cells mess with the body's defenses, and furthermore, how looking closely as those messes might (might) tell us something about the likelihood of a patient's survival and/or transformation to an aggressive lymphoma.
The researchers knew (as we all do) that cancer cells do a fantastic job of tricking the body's natural defenses into thinking that everything is OK, allowing the cancer cells to grow unchecked. Normally, an invader or a threatening cell is destroyed by an immune system cell, either a B cell or a T cell. These reserchers looked specifically at a kind of T cell called a TIL (Tumor-Infiltrating T Cell), which is a T cell that leaves the bloodstream (where they hang out an wait) and attaches itself to a tumor. They took TIL samples from biopsies from 172 Follicular Lymphoma patients before they had treatment, and compared them to healthy T cells from 12 people who were lucky enough to not have cancer. They found that the TILs had several genetic changes, compared to the healthy T cells.
Then they went a step further, and exposed the healthy T cells to Follicular Lymphoma cells, and found that the cells changed in the same way. So, clearly, the Follicular Lymphoma cells have something to do with the genetic changes. In addition to messing with their genes (and making them less effective), the healthy cells also had decreased mobility, so they couldn't move to their target as easily as healthy T cells.
One last step: they looked at how many TILs were present, and where they showed up, and found that that number and location had a serious correlation to overall survival and the chances for transformation.
BUT -- the researchers are very careful to talk about the implications. Right now, there aren't any. It's just too early. The results help us understand just how complex the microenvironment is, and might give us some new clues about what's going on in there. But there will need to be a whole lot more done before we can figure out how this is going to lead to any treatments. For that matter, it will still be a while before we even know how all of this will help predict whether or not a patient will transform.
So, as I said, interesting, but very early research.
I see it as another small piece of a 10,000 piece puzzle being put into place. Once we get the edges done, we can start to work our way in, and at some point, it all comes together.
Until then, patience and hope.
Sunday, August 11, 2013
Amazing Antibodies
Oncology Live published a great article this week on antibodies and their use in cancer treatment.
Of course, Rituximab (Rituxan), my bestest pal, among them, and the article credits Rituxan as being the first of the great anti-cancer antibodies, followed shortly by Trastuzumab, better known as Herceptin, used against breast cancer. Soon after that come Ibritumomab (Zevalin) and I-131 tositumomab (Bexxar), and then a bunch more. All of those "-mab" endings mean "monoclonal antibodies," of course, and there are a bunch more, with more to come.
The article gives a brief history of MABs, and it's fascinating. I know some things about Rituxan, since we're "besties" and all, but I didn't know about that Chinese Hamster Ovary cells, CHOs, are the most common cell line used to make MABs these days. Or that yeast and algae are being explored as ways to produce MABs even faster and cheaper. Kind of cool.
There's a nice chart of MABs that have been approved so far, and of a bunch more than are currently in phase III clinical trials. Those in the pipeline include Inotuzumab Ozogamicin, which targets CD22 in NHL (a phase III trial was actually cancelled in May, though other trials are ongoing), and Obinutuzumab (GA101), which has been getting some positive press lately.
I think the most interesting part of this article, though, is the discussion of the ways antibodies are being "redesigned" by researchers, to improve on their effectiveness by overcoming some of their natural limitations. These redesigns include:
Overall, this is a pretty nice introduction to the amazing world of antibodies.
Of course, Rituximab (Rituxan), my bestest pal, among them, and the article credits Rituxan as being the first of the great anti-cancer antibodies, followed shortly by Trastuzumab, better known as Herceptin, used against breast cancer. Soon after that come Ibritumomab (Zevalin) and I-131 tositumomab (Bexxar), and then a bunch more. All of those "-mab" endings mean "monoclonal antibodies," of course, and there are a bunch more, with more to come.
The article gives a brief history of MABs, and it's fascinating. I know some things about Rituxan, since we're "besties" and all, but I didn't know about that Chinese Hamster Ovary cells, CHOs, are the most common cell line used to make MABs these days. Or that yeast and algae are being explored as ways to produce MABs even faster and cheaper. Kind of cool.
There's a nice chart of MABs that have been approved so far, and of a bunch more than are currently in phase III clinical trials. Those in the pipeline include Inotuzumab Ozogamicin, which targets CD22 in NHL (a phase III trial was actually cancelled in May, though other trials are ongoing), and Obinutuzumab (GA101), which has been getting some positive press lately.
I think the most interesting part of this article, though, is the discussion of the ways antibodies are being "redesigned" by researchers, to improve on their effectiveness by overcoming some of their natural limitations. These redesigns include:
- Conjugates, where antibodies have something added to them, like radiation or chemotherapy. The antibody isn't used to destroy the cell, the way it is with, say, Rituxan, but rather to deliver a deadly payload, as with Zevalin. About half the antibodies being developed are conjugated types.
- Glycoengineering, where the antibodies are manipulated to change the sugars they contain, which affects how well they bind to their targets. GA-101 is a glycoengineered antibody.
- Fragmentation, where pieces of antibodies are used, because they penetrate solid tumors better. (Not really relevant to lymphoma, but interesting anyway.)
- Bispecification, where two different antibodies are combined into one. One example is Blinatumomab, also known as MT103. Very cool antibody; its two arms target different things -- the cancerous B cell, and the healthy attacking T cell. This allows the body's defenses to recognize the cancer cell and take it out. It's in phase II trials right now, and shows some promise.Blinatumomab (MT103)
Overall, this is a pretty nice introduction to the amazing world of antibodies.
Inotuzumab ozogamicin
Inotuzumab ozogamici n
Friday, August 9, 2013
Goodbye, Bexxar
Sad news today for lymphoma patients: GlaxoSmithKline is discontinuing its production of Bexxar, the RadioImmunoTherapy treatment that was so helpful to lots of Follicular Lymphoma patients.
There hasn't been a whole lot of fanfare about it; google "Bexxar" and there aren't any press releases or stories about it (at least as I am writing this). But the bexxar.com page does have a brief message near the top of its homepage, that says
That's about it. Though Lymphoma Rock Star Jamie Reno does have an extensive piece on his site about Bexxar and the implications of its discontinuation for all of us. Reno's Follicular Lymphoma was treated with Bexxar in 1999, and he enjoyed a progression-free life for more than 13 years.It's a nice piece, and Reno's anger comes through very clearly.
It's probably not surprising, in some ways, that GSK made the decision. I've written a lot about RIT in the last 5 years -- both the promise it holds and the difficulties it entails. There are reimbursement problems with RIT, which stem from the way it is classified by Medicare. And it's not easy to administer -- not as easy as Rituxan, or most chemos, which can be given right in the oncologist's office. RIT, including Bexxar, needs to be administered by a nuclear medicine specialist, with help from a small team. Kind of a pain to put together, and most oncologists would just as soon do chemo and take care of it themselves. It never really gained the popularity that it should have.
It is also not surprising because GSK didn't seem to make much of an effort to expand its use, unlike the makers of Zevalin, Bexxar's RIT cousin. Zevalin has been involved in clinical trials in the last few years to allow more patients to use it. Bexxar didn't. So, if nothing else, Zevalin's name was out there more than Bexxar's, so more patients might have known about it.
The good news, as I wrote about last week, is that at least one new RIT version is in the pipeline. It has a short wavelength, which makes it (maybe) a little closer to Bexxar than it is to Zevalin. Not necessarily a Bexxar substitute -- I'm mostly looking for things to be positive about.
But overall, there isn't much positive to the news. When more arrows in the quiver bring us hope, this amounts to one fewer arrow.
(I can't end so negatively. There's still a LOT of arrows in that quiver.....)
There hasn't been a whole lot of fanfare about it; google "Bexxar" and there aren't any press releases or stories about it (at least as I am writing this). But the bexxar.com page does have a brief message near the top of its homepage, that says
GSK plans to discontinue the manufacture and
sale of the BEXXAR therapeutic regimen (tositumomab and iodine I 131
tositumomab). The last day to schedule dosing for BEXXAR will be
February 11, 2014 with final patient-availability on February 20, 2014.
For more information, contact the GSK Response Center at 1-888-825-5249
That's about it. Though Lymphoma Rock Star Jamie Reno does have an extensive piece on his site about Bexxar and the implications of its discontinuation for all of us. Reno's Follicular Lymphoma was treated with Bexxar in 1999, and he enjoyed a progression-free life for more than 13 years.It's a nice piece, and Reno's anger comes through very clearly.
It's probably not surprising, in some ways, that GSK made the decision. I've written a lot about RIT in the last 5 years -- both the promise it holds and the difficulties it entails. There are reimbursement problems with RIT, which stem from the way it is classified by Medicare. And it's not easy to administer -- not as easy as Rituxan, or most chemos, which can be given right in the oncologist's office. RIT, including Bexxar, needs to be administered by a nuclear medicine specialist, with help from a small team. Kind of a pain to put together, and most oncologists would just as soon do chemo and take care of it themselves. It never really gained the popularity that it should have.
It is also not surprising because GSK didn't seem to make much of an effort to expand its use, unlike the makers of Zevalin, Bexxar's RIT cousin. Zevalin has been involved in clinical trials in the last few years to allow more patients to use it. Bexxar didn't. So, if nothing else, Zevalin's name was out there more than Bexxar's, so more patients might have known about it.
The good news, as I wrote about last week, is that at least one new RIT version is in the pipeline. It has a short wavelength, which makes it (maybe) a little closer to Bexxar than it is to Zevalin. Not necessarily a Bexxar substitute -- I'm mostly looking for things to be positive about.
But overall, there isn't much positive to the news. When more arrows in the quiver bring us hope, this amounts to one fewer arrow.
(I can't end so negatively. There's still a LOT of arrows in that quiver.....)
Wednesday, August 7, 2013
Cancer Cup Song
If you listen to Top 40 radio, you've probably heard a whole loot of Anna Kendrick's song "When I'm Gone" lately. It's also known as "The Cup Song," because Kendrick sang it in the movie Pitch Perfect while accompanying herself with a plastic cup. (You can watch the scene here.) Cute scene, catchy tune.
A few weeks ago, a young bone cancer survivor named Carmen Diaz, 13 years old, rewrote the song to reflect her cancer experience, and made a video. It's worth embedding it here:
Her two partners are actually two of her doctors. She made the video in hopes of being on Ellen DeGeneres's show. Racer Jeff Gordon has actually offered to help her make that happen. I can't find anything on whether or not she's going to be on Ellen's show, but it sure seems like the kind of thing Ellen would love.
Awesome video. Good luck, Carmen.
A few weeks ago, a young bone cancer survivor named Carmen Diaz, 13 years old, rewrote the song to reflect her cancer experience, and made a video. It's worth embedding it here:
Her two partners are actually two of her doctors. She made the video in hopes of being on Ellen DeGeneres's show. Racer Jeff Gordon has actually offered to help her make that happen. I can't find anything on whether or not she's going to be on Ellen's show, but it sure seems like the kind of thing Ellen would love.
Awesome video. Good luck, Carmen.
Tuesday, August 6, 2013
PMC Thanks
A big congratulations -- and a bigger thanks -- to my brother Mike, who crushed this year's Pan-Mass Challenge ride this weekend.
Mike raised (as of this morning) $6,545 for cancer research at Dana-Farber in Boston. In six years of riding, he has raised over $38,000. Pretty awesome.
Unfortunately, I was not able to go this year to cheer him on, so I have no pictures. But from what I saw, he looked great.
Of course, even though the ride is over, it's not too late to donate. Visit his donation page at http://www2.pmc.org/profile/pfp.asp?profileid=MM0386. Think of it rewarding him for being awesome.
Thanks Mike. Keep pedaling.
Mike raised (as of this morning) $6,545 for cancer research at Dana-Farber in Boston. In six years of riding, he has raised over $38,000. Pretty awesome.
Unfortunately, I was not able to go this year to cheer him on, so I have no pictures. But from what I saw, he looked great.
Of course, even though the ride is over, it's not too late to donate. Visit his donation page at http://www2.pmc.org/profile/pfp.asp?profileid=MM0386. Think of it rewarding him for being awesome.
Thanks Mike. Keep pedaling.
Sunday, August 4, 2013
Transformed Follicular Lymphoma
Some good news from the upcoming Journal of Clinical Oncology: maybe transformation isn't as common among Follicular Lymphoma patients as we thought.
A reminder about transformation (though, if you're a Follicular Lymphoma patient, it's probably always in the back of your mind): Sometimes the nice, slow-growing Follicular Lymphoma turns into a less-good, faster-growing type of NHL, typically Diffuse Large B Cell Lymphoma, though occasionally something else equally nasty. Follicular Lymphoma is, according to the specialist I saw after I was diagnosed, "genetically unstable." It can change into something else.
Transformation is the worst nightmare of many Follicular Lymphoma patients, including me. It's more treatable the earlier it is detected, and we always wonder if that lump that popped up, or that weird cough, or that warm sweaty night is a sign of transformation. The fear gets less intense over time, but it's always there, at least a little bit.
Studies of the frequency of transformation are kind of inconsistent; I've seen statistics that show that anywhere from 15% to 50% of Follicular Lymphoma patients will eventually transform. I've also seen studies that show that show that transformation is virtually unheard of after 15 years, and others that refute that. So while I'm excited about what the Journal of Clinical Oncology article has to say, I'm also trying not to go overboard with my enthusiasm.
The article is called "Rates and Outcomes of Follicular Lymphoma Transformation in the Immunochemotherapy Era: A Report From the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource." Researchers from Iowa and Mayo looked at 631 patients (a pretty good number) who were newly diagnosed with Follicular Lymphoma. They observed them over time (a median of 5 years, with some observed for a little over 9 years), and they compared the rate of transformation to the overall survival rate.
They found some good things:
Enough of that. For now, let's take it for what it is -- another reason for hope.
A reminder about transformation (though, if you're a Follicular Lymphoma patient, it's probably always in the back of your mind): Sometimes the nice, slow-growing Follicular Lymphoma turns into a less-good, faster-growing type of NHL, typically Diffuse Large B Cell Lymphoma, though occasionally something else equally nasty. Follicular Lymphoma is, according to the specialist I saw after I was diagnosed, "genetically unstable." It can change into something else.
Transformation is the worst nightmare of many Follicular Lymphoma patients, including me. It's more treatable the earlier it is detected, and we always wonder if that lump that popped up, or that weird cough, or that warm sweaty night is a sign of transformation. The fear gets less intense over time, but it's always there, at least a little bit.
Studies of the frequency of transformation are kind of inconsistent; I've seen statistics that show that anywhere from 15% to 50% of Follicular Lymphoma patients will eventually transform. I've also seen studies that show that show that transformation is virtually unheard of after 15 years, and others that refute that. So while I'm excited about what the Journal of Clinical Oncology article has to say, I'm also trying not to go overboard with my enthusiasm.
The article is called "Rates and Outcomes of Follicular Lymphoma Transformation in the Immunochemotherapy Era: A Report From the University of Iowa/Mayo Clinic Specialized Program of Research Excellence Molecular Epidemiology Resource." Researchers from Iowa and Mayo looked at 631 patients (a pretty good number) who were newly diagnosed with Follicular Lymphoma. They observed them over time (a median of 5 years, with some observed for a little over 9 years), and they compared the rate of transformation to the overall survival rate.
They found some good things:
- The transformation rate after 5 years was 10.7%. That's the lowest I've ever seen in a study.
- They found that an increase in LDH (lactate dehydrogenase), a blood marker, was a signal that transformation was possible. This seems pretty standard; I've been reading about LDH levels since I was diagnosed.
- The transformation rate was was highest in patients who were "initially observed" (14.4%) and lowest in patients who initially received Rituxin (3.2%). I assume the "initially observed" means those who watched and waited; it's not defined in the abstract I'm linking to. That said, 14.4% is still relatively low among the numbers I have seen -- up to 50%, as I said above.
- The median overall survival after transformation was 50 months -- again, a pretty good number. However, survival was better in patients who had transformed more than 18 months after their initial Follicular Lymphoma diagnosis (66% overall survival at 5 years) than those diagnosed sooner than 18 months (22%).
- Their conclusion is very positive, however: In the Rituxan Era, transformation rates seem to be dropping, and survival chances are improving -- overall survival of transformed patients is on par with those who have not transformed. they speculate that initial treatment (that is, choosing Rituxan right away) may help (again, this is the first time I've seen any suggestion that initial treatment choice has any effect on transformation).
Enough of that. For now, let's take it for what it is -- another reason for hope.
Friday, August 2, 2013
What Causes Lymphoma?
New researcher out of Emory University: incidents of Non-Hodgkin's Lymphoma are higher among people who live in regions near facilities that release benzene into the environment. Benzene is used as a solvent, is a component of some fuels, and is used in a whole lot of industries. Seems kind of tough to me to even nail down where it might come from.
The researchers make clear, though, that benzene exposure won't necessarily translate into developing lymphoma. It's a population study, looking at trends in incidents of the disease and distance from benzene release sites, not a study of individuals who were definitely exposed to benzene.
It's kind of hard, really, to make that kind of connection for lymphoma -- to say, Hey, you worked with this chemical, or that pesticide, or you were exposed to that amount of radiation, so that's what caused your follicular lymphoma (or whatever).
And I'm not convinced it's even worth knowing, unless you can know for sure.
A few weeks ago, someone wrote to the support group, asking people what caused their lymphoma. Some people knew (or claimed to know) for sure. Others were less confident, but willing to speculate anyway. And some of us (me included) just don't know.
Here's the problem that I have with the question: if we don't know for sure, what good comes from speculating? A whole lot of things can possibly cause lymphoma. If I get diagnosed, and I look back and identify something I did that might have caused it, can I end up feeling anything but guilt? That time I worked as a housepainter to help pay tuition -- could that have done it? Should I have taken a different job? Was it the radiation I received when I caught that other tumor early? Should I have held off and insisted on a different type of treatment, less effective but "safer"?
We make choices. We can't change the past.
To me, lymphoma patients have enough negative emotions to deal with. We don't need to add guilt or regret.
If I made a choice years ago, and I knew, absolutely, without doubt, that it caused my follicular lymphoma, then I'd want to know, because I'd devote a big chunk of my time to making sure others didn't make that same choice.
But I have no idea.
So I focus on the present, doing what I can to stay informed and do what I can to make good choices from here.
I suggest you do the same.
The researchers make clear, though, that benzene exposure won't necessarily translate into developing lymphoma. It's a population study, looking at trends in incidents of the disease and distance from benzene release sites, not a study of individuals who were definitely exposed to benzene.
It's kind of hard, really, to make that kind of connection for lymphoma -- to say, Hey, you worked with this chemical, or that pesticide, or you were exposed to that amount of radiation, so that's what caused your follicular lymphoma (or whatever).
And I'm not convinced it's even worth knowing, unless you can know for sure.
A few weeks ago, someone wrote to the support group, asking people what caused their lymphoma. Some people knew (or claimed to know) for sure. Others were less confident, but willing to speculate anyway. And some of us (me included) just don't know.
Here's the problem that I have with the question: if we don't know for sure, what good comes from speculating? A whole lot of things can possibly cause lymphoma. If I get diagnosed, and I look back and identify something I did that might have caused it, can I end up feeling anything but guilt? That time I worked as a housepainter to help pay tuition -- could that have done it? Should I have taken a different job? Was it the radiation I received when I caught that other tumor early? Should I have held off and insisted on a different type of treatment, less effective but "safer"?
We make choices. We can't change the past.
To me, lymphoma patients have enough negative emotions to deal with. We don't need to add guilt or regret.
If I made a choice years ago, and I knew, absolutely, without doubt, that it caused my follicular lymphoma, then I'd want to know, because I'd devote a big chunk of my time to making sure others didn't make that same choice.
But I have no idea.
So I focus on the present, doing what I can to stay informed and do what I can to make good choices from here.
I suggest you do the same.