Saturday, December 20, 2014

Patient Power on ASH

OK, I have a confession to make: I've been unfaithful.

I was doing so well with posts this month, and now I'm seeing that I have only posted once in the last 10 days.

And it's because I've been busy with another aspect of my online life. It's been pulling me away from Lympho Bob. As much as I love reading and writing about cancer (really, who wouldn't?), it's new and fun and exciting and taking my time. All that has slowed down a little bit for now, so maybe I can go back and read and write about all the stuff I have saved that deals with Follicular Lymphoma.


So here goes:

The good folks at Patient Power have been posting their annual follow-ups to the ASH Conference. Not much (at least not yet) on Follicular Lymphoma, though this short interview with Dr. Ajay Gopal of the Seattle Cancer Care Alliance does mention FL, and results from research on Idelalisib/Zydelig. It's a brief mention, but nice to hear. (Sounds like CLL and Hodgkin's are the big winners at ASH this year.)

While I was at Patient Power, I did a little searching around, and I found an interview about the ASH Conference in 2007 with Dr. Mark Kirschbaum of the City of Hope National Medical Center.

What was so interesting to me was that this interview happened about a month before I was diagnosed.

Dr. Kirschbaum discusses a clinical trial for an inhibitor  that had good results. He was very interested in alternatives to standard chemotherapy, especially epigenetic agents that target processes that cancer cells rely on, rather than chemos that kill the cells. He didn't name the particular treatment, but looking at the the ASH abstracts, it seems to me that he was probably talking about Vorinostat (also known as Zolinza!).

Vorinostat/Zolinza! was in a phase 2 clinical trial in 2007, and seemed to have pretty good results.

Last March, I wrote about Vorinostat/Zolinza! being in a phase 2 clinical trial.

Eight years, and it seems like we haven't made any progress there. (But I'm sure if looked into more deeply, I'd find out why.)

It's a nice reminder that, as excited as I get about new research that I come across, it takes a long time for a treatment to get from a lab to the oncologist's office. We've come a long way in the time since I've been diagnosed, but there's plenty of work that's been done that hasn't gone anywhere -- not even to the phase 2 clinical trial that Vorinostat/Zolinza! has seen.

(Zolinda! doesn't officially have an exclamation point at the end of it, but as I wrote in March, it really should.)

Anyway, this little trip through history isn't going to stop me from getting excited, and it shouldn't stop you from getting exciting, either. There's still plenty of great stuff out there. And I'm going to keep writing about it.

Monday, December 15, 2014

Up-to-date Info on Transformed Follicular Lymphoma

Blood journal recently published an article called "Transformed Follicular non Hodgkin Lymphoma," by Carla Casulo, W. Richard Burack, and Jonathan W. Friedberg of the James P. Wilmot Cancer Center at the University of Rochester Medical Center. I believe it gives as up-to-date information about Transformed Follicular Lymphoma as is possible to give.

As Follicular Lymphoma patients, Transformation might be as scary as it gets. Our often slow-growing, well-behaved cancer turns nasty and aggressive. We've probably all seen statistics and heard nightmare stories about Transformation, and they haven't helped us feel any better.

I can't say the Blood article tells us we have nothing to worry about (which would have been nice), but it does offer lots of review of previous studies, and does point to some hopeful developments that might shed some light of Transformation in the future.

I'm not going to summarize the entire 30 page article, but I will give you what I think are some of the highlights:
  • We often think of Transformed Follicular Lymphoma as "binary." In other words, one day you have FL, and then the next you have DLBCL. Those same cells just switch from one type to another.  However, with better tools, we can see genetic differences in FL cells, and when researchers compare FL cells from before a transformation to those after a transformation, they find that there are several "drivers" in the cells. In other words, any of those things could be the cause of the transformation. It's possible that we actually undergo several transformations during our time with Follicular Lymphoma -- not necessary to an aggressive lymphoma, but to different types of Follicular Lymphoma. This makes a lot of sense -- it could explain why the disease keeps coming back, and why it is resistant to some treatments, but not others. So it's possible that researchers can identify those different mutations in each patient, at each stage of their disease, and use a targeted treatment to more effectively get to the problem.
  • There is probably not one single driver that transforms indolent FL into something more aggressive. But they are beginning to identify some of those drivers. The good news is that they seem related to a lot of the newer treatments we keep reading about, like immunotherapies and pathway targets.
  • As for predicting whether or not someone's FL might transform, there have been some mixed results. Studies have shown that there might be a micro-environment issue that allows transformation to happen, or that blocks the immune system from stopping it, but the evidence available so far kind of contradicts itself, so it's hard to say for sure.
  • As for confirming that a patient has transformed, the "gold standard" is a biopsy that looks at the cells and sees that they have changed. However, clinical symptoms seem to be just as accurate: increased swelling of nodes, disease spreading to sites other than the nodes, rising LDH levels in the blood, etc. PET scans are also used to confirm transformation. All of them are fairly accurate, so a biopsy isn't absolutely necessary if a biopsy site it hard to get to, or things are progressing so rapidly that time is an issue.
  • As for the question of the risk of transformation (what percentage of patients will transform), the authors note that studies have been all over the place, with overall risk at anywhere from 24% to 70%. However, most recent studies seem to confirm that 2% to 3% of patients will transform each year. Some studies suggest a plateau at 16 years, meaning, if you didn't transform by then, you probably aren't going to. More recent studies have focused on patients in the Rituxan Era, with the same 2% to 3% figure, which means Rituxan doesn't seem to affect transformation. It is more likely some genetic factor unaffected by Rituxan.
  • Can risk be lessened? That is, is there less chance of transformation if the patient has R-CHOP early on, or Rituxan Maintenance, or some other treatment? The answer is No, or at least, we're not sure. Some studies suggest it's a possibility, but others say it isn't.
  • However, Rituxan does seem to improve Overall Survival. Before Rituxan, survival was 1-2 years, and now, chemo-immunotherapy (say, R-CHOP) leads to Overall Survival of 4-5 years. (Median OS of 5 years in one study was 73%, about the same as non-transformed DLBCL).
  • There is some suggestion that Transformation soon after diagnosis led to worse outcomes than Transformation later on, though there's no real standard definition of what "earlier" and "later" actually mean, so it's hard to hold on to that one.
  •  Patients who have transformed are (according to the authors) often excluded from clinical trials, so it's difficult to get hard data on which treatments work best. That said, it seems like high-dose chemotherapy, followed by an Autologous Stem Cell Transplant (with the patient's own stem cells being harvested and reintroduced after chemo) is the most effective option. (The authors review a whole bunch of studies related to this option.) Less well studied are Allogeneic Stem Cell Transplants (where the patient receives a donor's cells instead of her own.) While Allo SCTs also have some success, there is also the risk of Graft versus Host Disease (where the body rejects the foreign cells -- not a problem with an Auto SCT).
  • There have been some attempts to incorporate RadioImmunoTherapy (RIT) into an Allo STC regiment. 
  • The authors note that newer treatments like Lenalidomide (Revlimid), Ibrutinib, Idelalisib, and others hold lots of promise for Follicular Lymphoma, DLBCL, and thus perhaps Transformed FL. Because we are learning more about the pathways that these treatments target, there's a good chance that we may find that those pathways are involved with Transformed FL.
  • As for the future, the authors say that "the two most prominently deregulated pathways in HT [Histologic Transformation] involve apoptotic resistance and epigenetic modification, two seemingly promising targets, for which trials are already underway (ie, GDC-0199/ABT199)." In other words, the things that likely cause Transformation already have treatments being studied. 
  • Finally, the authors discuss their own approach to treating Transformed FL. First, they use PET scans to choose the best site for a biopsy (they choose the one that is most aggressive). From there, if the patient has not yet had CHOP (or another treatment with anthracycline, which can damage the heart if used too much), they try 6 cycles of R-CHOP. They then follow up with High Dose Therapy and an Auto Stem Cell Transplant, if the patient is young and fit enough, and had prior treatment for FL. If this is a first treatment, they may follow the R-CHOP with Rituxan Maintenance. Older or less fit patients may have R-CHOP followed with RIT.
You're caught up now. As I said, it doesn't tell us we don't have to worry. But it's nice to see a lot of this stuff in one place, and it gave me some stuff to look forward to. Not bad for something so scary.

Wednesday, December 10, 2014

ASH Preview with Dr. Bruce Cheson

ASH is just about over now. I may sift through a few more abstracts to see if there's anything good that I missed, but we're in that phase now where presenters have been issuing press releases about whatever work they presented at ASH, crowing about the great things they found. (And they deserve to crow.)

One thing I missed posting, though, was Medscape's annual preview of the ASH conference. As always, it was presented by Dr. Bruce Cheson of Georgetown University.

As you may know, I'm very fond of Dr. Bruce Cheson(also known on Lympho Bob as Lymphoma Superstar Dr. Bruce Cheson). I like his work a lot, and I appreciate his thoughtful and critical look at research. he always manages to give me a different perspective on things.

And he's also really entertaining. I think the last time I posted something about him, it was a video of a presentation he gave at a dinner, and he brought his glass of wine right up with him to the podium. (It turned out he had a reason for that, but it was for a good reason.)

 His 2014 ASH preview was just as informative, and entertaining. You can find it here, though you need to sign up for a Medscape account in order to view it.

If you don't have or want a Medscape account, I'll say that the entertaining part came right away. The ASH meeting was in San Francisco, so he opened his video preview by weaving in the lyrics from Scott McKenzie's 1967 summer of love hit "If You're Going to San Francisco."  I hope the good doctor did indeed find some gentle people with flowers in their hair at ASH.

In the video, Dr. Cheson's discussion of Indolent Lymphomas shows he is excited about the phase II trial of Ibrutinib, and about results from the R-squared trial (Rituxin and Revlimid), which wasn't presented at the ASH conference, but which should be coming soon. He also is interested in some of the work that has been done with PET scans, which, as he notes, have been controversial lately.

And if you need a little more entertainment, I liked his Dr. Cheson's video from last year on the virtues of hummus (especially the title).

All in all, I think ASH was a success for Follicular Lymphoma this year. No huge breakthroughs, but lots of smaller things that will help us in the future -- near-term and far-term.

Monday, December 8, 2014

ASH: Understanding Follicular Lymphoma

I've been writing about some of the abstracts for the ASH Meeting, looking ahead to it, but at this point, we're right in the middle of it. It started on Saturday and runs through tomorrow. And it's huge -- I read a brief article from someone who is not in the medical field who is attending with his wife, who is a hematologist. The writer was overwhelmed at how large the ASH meeting is. He says there are about 18,000 physicians and researchers there, plus another 9000 or so people who work for pharmaceutical, medcial supply, and other related companies. ASH is clearly a big deal.

I've been avoiding some of the more technical abstracts that don't have fairly immediate payoffs for patients. I like to focus on treatments, and other things that make me feel good and are easy to relate to my, and your, situations.

But there's a lot of really interesting stuff at ASH about the biology of Follicular Lymphoma -- how it all actually works. And of course, this is important, too, because none of those treatments would be here if we didn't know something about how Follicular Lymphoma cells behave and interact with their environment. The research on cancer has been pretty explosive over the last 10 years or so, with huge advances, compared to what we knew before then. It's no coincidence that the Human Genome Project announced in 2003 that it had mapped the human genome. Once we had the map, it got a lot easier to start exploring the terrain, and we're seeing the results now (and have been for a few years).

So I want to give a quick review of some of the more biology-heavy ASH presentations on Follicular Lymphoma this year. You Cancer Nerds might enjoy the links to the abstracts, but I think all of us can at least get a sense of how much we're coming to understand what makes Follicular Lymphoma work, and maybe how that can help researchers fight it:

  • In "Multiparameter Microscopy Analysis of the Follicular Lymphoma Microenvironment and Normal Germinal Centers: In Vivo evidence That Follicular Helper T Cells Form Synapses with Neoplastic B Cells and Are Associated with Proliferation and Expression of Activation Induced Cytidine Deaminase," researchers looked at Follicular Helper T Cells, and the role they play in Follicular Lymphoma. T Cells are part of everyone's immune system. The T Cells in this study play a role in activating B Cells (another important part of a normal immune system) and allowing them to multiply and attack invaders. However, when the T Cells are off target (they interact with the wrong thing), they might trigger mutations that lead to FL. So, good T Cell work = lots of good B Cells. Bad T Cell work = lots of bad B Cells. (And, in  case you forgot, Follicular Lymphoma is a B Cell cancer.) Understanding this process might lead to treatments that target the process and make it stop behaving badly.
  • The study "Intratumoral and Peripheral Blood T Cells Recognize Mutated Neo-Antigens in Follicular Lymphoma" is another look at T Cells and how they might fight Follicular Lymphoma.T Cells work by recognizing antigens -- stuff that isn't supposed to be in us. Antigens are matched up with antibodies, which fight them off. The fight is a lot easier if we already have an antibody that recognizes the antigen (which is why we get flue shots -- so we can build up some antibodies that will recognize the flue antigen if we get it). In this study, researchers wanted to figure out if T Cells could recognize FL cells as neo-antigens -- new invaders that need to have antibodies created to fight them. Indeed they do recognize them as neo-antigens. This means there could be personalized vaccines created, using manipulated T Cells to find those FL cells. It could also mean that other immunotherapies could be developed to help the body fight them off naturally.
  • "Genomic Diversity of Newly Diagnosed Follicular Lymphoma: A Pilot Investigation" tries to take a wider look at the genomic changes in Follicular Lymphoma, looking for new biomarkers that might indicate differences in various Follicular Lymphoma samples. In other words, we know that all FLs are not the same, and we know that the (14,18) chromosome switch is one way to identify Follicualr Lymphoma -- but are there some other ways to identify it? And can those ways tell us something about how the FL will behave? The answer is yes, and some of the biomarkers seem to predict whether an FL will be indolent or more aggressive. You can look at the abstract for more deatils, you big cancer nerd, you.
I really just wanted to give a quick sample of some of the more science-heavy work being presentde at ASH. There's a lot more than just this, but these few should give you a sense of how much more we're learning about Follicular Lymphoma, and how that new knowledge might translate into new treatments.

But all that is down the road a ways. Maybe in a few years, we'll see the phase 1 results of all of this good, important stuff.

Friday, December 5, 2014

Goodbye, Dr. R

As you probably know, I got a letter a couple of months ago from my beloved oncologist, Dr. R, letting me know that he was leaving the practice and moving out of state. I did some initial research on replacement possibilities right after I got the letter, but then I kind of put it out of my mind. I didn't want to deal with it. It made me sad.

On Monday, I got a phone message from Dr. R's secretary, saying she wanted to chat with me. I avoided that call, too -- I finally got back to her on Wednesday.

(Have you noticed that I'm really good at avoiding unpleasant things? Is it any surprise I did so well Watching and Waiting?)

I had an appointment scheduled for a few days after Dr. R was going to be leaving, and his secretary wanted to try to get me in before then. She gave me a few open times, and I was able to take one yesterday morning.

I was kind of dreading it.

I did my blood work and other vitals, and then got in to see him pretty quickly. I got the details of his leaving: he got an opportunity to take a teaching position in another state, and he and his wife decided it was a good time (and a good place) for a move. I reminded him that I told him a few years ago that he should be teaching, after he got an offer to do a little teaching in a local nursing school. He's patient, and good at explaining things. So I approve of the move.

I also got the impression that there are some small issues with the practice, which went from private to being affiliated with a teaching/research hospital a couple of years ago. Nothing that would have pushed him out, but just another reason to say this is a good time for a move. I've seen changes in the practice, too, from my position as a patient, so it doesn't surprise me that there is some stuff going on from his end as well.

We also talked about the possibility of my staying in the practice (which is pretty likely, since there aren't a whole lot of oncologists in the area that aren't part of the practice). I go to one of 6 different offices in the area only because Dr. R works there. He thinks his replacement would be fine for me, but thinks I might be happier in an office closer to my home (which I agree with).

I told him I'd really like to see a Hemotologist, or at least someone who has a particular interest in Lymphoma, rather than just a generalist (which is what his replacement will be). "It took me 3 or 4 years to train you," I told him. "I don't have the time to train someone else in Follicular Lymphoma." He laughed, probably remembering that he had a fellowship in Hematology at a prestigious hospital before I met him.

He told me about the oncologists in the office that he was suggesting I go to. One doesn't seem to match up with my and Dr. R's shared philosophy of not doing more than is necessary (Watch and Wait; Rituxan instead of chemo), but the others in that office seem like they'd be fine. (In fact, two of them were on my list of possibilities from when I did some research after I got his letter.)

So I feel OK about where I may go from here. I trust his judgement.

Of course, this was a regular office visit, too, so I should report on that:

Blood work is good. No new nodes popping up anywhere. I feel fine. No appointment necessary for another 4-5 months.

But this time it will be with a new oncologist.

I shook his hand and said goodbye, and thanked him for being a good doctor for me. I resisted the urge to hug him, because I think it would have made him uncomfortable.

I stooped by to talk to his secretary, who told me what would happen from here with the new office. I'll hear about an appointment in the next few weeks.

And then I left.

And I'll be honest, I got a little teary in the parking lot.

I've probably seen two dozen doctors of all kinds on my adult life, but I've never had that reaction with any of them. Mostly, if I have to switch doctors, it's mild annoyance that I have to go look for someone new.

But Dr. R was different. Not just because he is an oncologist. He's also a kind man, and everyone in his office was the same, from the receptionist to the phlebotomist to the nurses. I can't imagine what it's like to be in oncology, whatever the position. It takes a special person to stay that upbeat in the face of sometimes difficult circumstances. Dr. R and his staff knew me. They remembered the things I told them, they asked about my kids, and they knew it all even if I didn't see them for months.

I'm going to miss them all, but especially Dr. R.

But we move on because we have to. And I will move on.

Wednesday, December 3, 2014

ASH: Watching and Waiting (We're Still Talking About This)

It's amazing how some topics just won't go away.

Watching and Waiting is one of them. It's especially interesting to me because I watched and waited for two years. I suppose I shouldn't really care anymore, since that ship has long since sailed, but I'm still interested in what research has to say about whether or not I made the right choice. (It certainly seems like I did, almost 7 years later....)

Researchers at the National Cancer Center Hospital in Tokyo are interested in whether or not Watching and Waiting is still a valid strategy in the Rituxan Era. This has been the way the subject has been thought about for a while: the idea behind watching and waiting was that it was better to do nothing because the alternatives could do harm (when the alternatives were traditional chemotherapy). But with Rituxan, and its minimal side effects, is there really a reason to wait? Another reason for W & W: with a limited number of available treatments, isn't it better to hold them in reserve until absolutely necessary? But now, we have so many new treatments available and in the pipeline, why not just treat immediately?

There have been lots of responses to those questions in the last 5 years or so, with answers on both sides. But neither side has been able to come up with research that shows that their side is the winner of this debate.

So the latest attempt, to be presented at ASH, says this:

The study looked at 348 patients treated between 2000 and 2012 (101 watched and waited, and 247 were treated immediately). Of the Watch-and-Waiters, 45 patients received treatment for lymphoma within a median of 16 months. Looking at Time to Treatment Failure (how long it took until a second treatment was needed), the 45 who had watched and waited before treatment had a TTF of 92 months, while the patients who had immediate treatment had a TTF of 85 months. Statistically, there's no difference between them. Other measures had the same result: Overall Survival was essentially the same between the groups, and so was risk of transformation.

So, basically, there is no negative impact to Watching and Waiting, at least in looking at these particular factors, for this particular population. That seems to be about the same result that we've kept getting for the last five years.

Of course, the numbers don't really tell the whole story when it comes to deciding whether or not to watch and wait. Numbers can tell your head that it's an OK choice, but there's an emotional aspect to that decision, too. If you think you can handle the not-knowing, and you don't feel the need to just do something, then watching and waiting is an especially valid choice. But that's a hard thing to measure with numbers, especially in the heat of a new cancer diagnosis. That's got to come from deep inside.

So it's good to know that I made an OK choice seven years ago. Not that I would have regretted it if the numbers have come out differently. No point in regretting our choices. We have enough to worry about without adding guilt to it.....

Sunday, November 30, 2014

ASH: Young Folks with Lymphoma

If you have read enough of Lympho Bob, you know I was diagnosed a few months after I turned 40.

I've seen a few studies of "Young Adults" who have been diagnosed with Follicular Lymphoma, and the usual definition of "Young" is under 40. Personally, I felt pretty dang young when I was diagnosed. Cancer is for old people, and this particular cancer was especially for old people, typically diagnosed in those over 60.

Well, I have found a study that defines "Young" as 18-40. Woo hoo! 40 is young!

(Of course, I'm closer to 50 now, and feeling old, but we'll ignore all of that.)

Another of the interesting ASH abstracts is called "Disease Characteristics, Treatment Patterns, and Outcomes of Follicular Lymphoma in Patients 40 Years of Age and Younger: An Analysis from the National LymphoCare Study," written by a bunch of researchers from impressive institutions all over the U.S.

They call Follicular Lymphoma in the 40 and under crowd "extremely rare," and point out that little is known about disease characteristics and outcomes for this group. They looked at 164 Young Adult patients in the National LymphoCare Study (about 6.2% of the total).

As for treatments, 19% did watch and wait, 12% got straight Rituxan, and 47% got some kind of chemo + Rituxan (about 61% of that group got R-CHOP).

As for outcomes, Overall Survival at 2 years was 97.4%, and at 5 years, 93.7%. After 7 years, it was 92%. Those are pretty good numbers. In fact, the researchers call them "outstanding."

What's really interesting was that they compared the numbers to people who had been diagnosed between the ages of 41 and 60 -- you know, older folks.

They found that the survival numbers were pretty much the same.

In other words, younger patients really don't need to be treated any differently than older patients.

I think that's encouraging for younger folks. While there haven't been a lot of  studies that have looked at them (us) directly, there was some slight worry that younger patients might have more aggressive disease. That doesn't appear to be the case.

And it's encouraging for the Old Timers, too. Just in case you thought those young folks were somehow better off  than you, that doesn't seem to be the case.

And the really encouraging thing is those "outstanding" Overall Survival numbers. There's no guarantee, of course, that our disease will ever behave like the statistics say it will. But if you're young and looking for a reason to be happy, that's a good one to hang on to.