Biggest Follicular Lymphoma Story of 2014

Last year, on the eve of the new year, I gave you my 10 "Best of 2013" stories for Follicular Lymphoma. As much as I'd like to do that again, it's not going to happen. Frankly, it's too much work. And in a year when wrote about 30 fewer posts than the year before, it just seems appropriate that I take the lazy way out at the end of this year, and give you my one Biggest Story instead of a Top 10.

There were some worthy candidates, for sure. Early in the year, we got the FDA approval for Idelalisib for Indolent/Follicular Lymphoma, through a "Breakthrough Therapy" designation. Very significant for both the promise of the treatment and for the FDA designation.There was good news in the spring for R + R, and for Velcade, both coming out of the ASCO conference. Bunch of stuff on vaccines, and tons on various inhibitors.

Then, of course, there's the big story on me personally: my biggest health problem of the year is not my lymphoma. (My shoulder, by the way, is doing well. Range of motion and strength are almost completely returned -- a very happy outcome, given my age and the damage I did.)

So, there's lots of good stuff in the world of Follicular Lymphoma this year. Lots that we can be hopeful about.

However, the one thing that continues to guve me the most hope is this:

Immunotherapy.

This isn't about one particular treatment, but instead a general approach -- trying to get the body's immune system to fight cancer on its own, instead of mistakenly recognizing cancer as something that's OK to let hang around. That can happen in a lot of ways.

Last year, the journal Science named Immunotherapy its "Breakthrough of the Year for 2013," and I'm aware that Immunotherapy isn't something new to this year. But a lot of the stuff I highlighted all year (including some of the stuff above) falls under the heading "Immunotherapy." (I'm going to send you, once again, to Lymphomation.org, if you want to know more about Immunotherapy.)

You want the line up? Monoclonal Antibodies, like Rituxan and some of the newer ones like Ofatumumab, are all considered Immunotherapies. (Not to mention to RadioImmunoTherapies that rely on MABs to find FL cells.) So are T-cell therapies, like Chimeric Antigen Receptor T-Cells (CAR-T). And so is Lenalidomide, the other R in R + R (it's also known as Revlimid). 

Really, most of the stuff that gets experts excited falls under Immunotherapy in some way. It's how we will deal with Follicular Lymphoma (and most cancers) for the foreseeable future: targeted treatments that work with the immune system to shut down cancer.

After the ASH conference this year, most of the press releases that I saw from research centers and pharma companies were touting the results of research on Immunotherapy of some kind. Arguably the biggest news to come out of ASH this year dealt with Immunotherapy approaches to Hodgkin's Lymphoma: two different treatments that targeted PD-1 had great responses from HL patients.

And if you aren't excited about Hodgkin's, there's the CAR-T results from a small trial at UPenn that showed a 100% response rate for Follicular Lymphoma patients....

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Immunotherapy isn't new, and it isn't one particular thing,and it's probably  a ways off before it replaces what we have now. And depsite that UPenn result, nothing is 100% effective -- not yet, anyway.

But on New Year's Eve, as we look back over our (surgically-repaired) shoulder, and think about the past, we look quickly ahead to the future. There's a lot to be hopeful about. New perspectives, new approaches, new results.

I wish you all, once again, much joy and peace in the new year. I thank you for reading over the last 12 months, and I look forward to sharing more great news with you in 2015.

The Best First Line Treatment for Follicular Lymphoma?

If you have paid any attention to Follicular Lymphoma treatments, you know that there is very little agreement among experts on which treatment is best to try first, which is best after that, etc. Watch and wait? Straight Rituxan? CHOP or Bendamustine? Newer treatments are making those questions even harder to answer.

Researchers in Italy have made the most recent attempt at an answer. Their article "The Use of Anthracycline at First-line Compared to Alkylating Agents or Nucleoside Analogs Improves the Outcome of Salvage Treatments After Relapse in Follicular Lymphoma The REFOLL Study by the Fondazione Italiana Linfomi" appears in the January 2015 issue of the American Journal of Hematology.

(I can't get access to the full article; I'm working from the abstract, which is linked above.)

Basically, they want to know if using certain types of treatments are more successful than others when used as a first treatment for FL, because they improve the treatment that comes right after that (salvage treatment). They looked at the records of over 500 patients to find an answer.


They compared three types of treatments: alkylating agents, which mess with DNA (these include Bendamustine and Cyclophosphamide, the "C" in CHOP and CVP); anthracycline (also known as Doxorubicin or Hydroxydaunomycin -- the "H"in CHOP); and nucleoside analogs, which mimic pieces of DNA and get in the way of cancer cells reproducing.

I don't have the names of specific treatments used in the study, but my guess is that they used CVP for the alkylating agent, CHOP for the anthracycline, and Fludarabine for the nucleoside analog. Just a guess.

(By the way, if you want t know more about these different types of chemotherapy agents and combos, Lymphomation.org does a nice job of laying them all out and making sense of the alphabet soup that chemo treatments often come to us as.)

What they found was that anthracycline (CHOP) did the best job, with the longest time-to-next-treatment. It didn't matter if the CHOP included Rituxan or not, and it didn't matter what the salvage treatment was (Rituxan Maintenance and Auto Stem Cell Transplants were among the possibilities).

Their conclusion: "This study supports the concept that in FL previous treatments significantly impact on the outcome of subsequent therapies. The outcome of second-line treatments, either with salvage chemoimmunotherapy or with autologs stem cell transplantation, was better when an anthracycline-containing regimen was used at first-line."

I've said this before, but it's worth saying again: this is great to know, but I wonder how much longer it's going to matter.  More and more lymphoma experts are telling us that traditional chemotherapy is on its way out. This study, which looked to the past for its data, is telling us something that just might not even be an issue in a few years. So I'm not sure we should be in a hurry to ask for CHOP when the time comes for treatment. I'm not certain, as I said, but I don't even think Bendamustine was used in this study. That would have to skew the results some, given what we know about B-R compared to CHOP.

The study's assumption is important: it assumes that the best first treatment is the one that takes the longest to get to a next treatment. And I think that assumption is on its way out, too. More and more newer treatments are focused on assuming that Follicular Lymphoma will be a chronic disease, one that we manage, not that we push off. In other words, we'll take a daily pill for years, rather than a few months of chemo and then wait it out.

On top of all of this, what we know about Transformed FL seems to indicate that CHOP, followed by an Auto SCT, might be something to hold off on, best used for Transformation, rather than as a first treatment for an indolent disease. That's debatable, of course, but something to be considered before declaring CHOP/anthracycline as the best first treatment.

If nothing else, this study highlights that we're at a crossroads for Follicular Lymphoma treatment. We'll see new ways of treating, and they'll come with whole new sets of assumptions about how and when to treat.

It's going to be an interesting few years for all of us....

Merry Christmas

For those of you who celebrate it, I want to wish you a Merry Christmas.




For those of you who do not (and really, for those of you who do, too), I want to wish you just a little more daylight.

A few days ago, we celebrated the winter solstice, the day (where I live, anyway) when we have the least amount of daylight. It's the official start of winter, when everyone grumbles about the snow shoveling that will inevitably come in the next few weeks. It's the day we start to hunker down and bury ourselves in blankets and pray for winter to be mild and quick.

But winter solstice, the day when we have the least amount of daylight, is also the last day that the daylight lessens. The next day, we have just a little more daylight. And the next day, just a little more. And then a little more.

The first day of winter isn't a day to grumble, it's a day to celebrate -- things get better from here, just a little more each day.

So whether today is Christmas for you, or just another winter day, I hope that small extra slice of daylight brings you just a little joy, and things get better for you every day -- even if it's just a little.

And for my friends in the Southern hemisphere -- read this again in six months.

And peace and joy to you, too.

Playing the Cancer Card

Susan Gubar, a wonderful writer and teacher. has a piece in the New York Times called "Living with Cancer: Playing the C Card." It's about playing that card, using cancer as an excuse -- a good excuse or a bad one -- to do something we want to do -- or avoid something we don't.

It brought back a couple of memories.

I have written a lot about playing the C card. I do it a lot less now, but when I was first diagnosed, I was a frequent player.

I remember, just  a few days after I was diagnosed, when my Mom and Dad came to visit. They were eager to come right away, as soon as I told them about the diagnosis, but we asked them to hold off for a couple of days, until we had more information, and they could be with us when we told the kids (my wife's excellent idea). They arrived on Friday afternoon. They were downstairs playing with the kids; I was keeping myself busy, making dinner and setting the table. I was a couple of minutes from serving when my mom came to the kitchen to see if she could help. She saw the set table and the food being put into dishes. "Oh, you did it already," she said, little guilty.

I played The Card:

"Yeah," I said. "Nice. Make the guy with f---ing cancer do all the work." She laughed, as I had hoped she would, and then hugged me. "Oh my God," she whispered. "Who would have ever thought we'd be laughing about cancer?" I hugged he back and told her we shouldn't ever stop.

A few years later, after her own cancer diagnosis, the family was at a Pawtucket Red Sox baseball game. She and I went to get ice cream. We waited in line for soft ice cream, served in a miniature helmet. I whispered to her, "If you tell him you have cancer, he might give you free sprinkles on your ice cream. That's what I'm doing." She laughed. "No!" she said. "Don't embarrass the kid!"

But after she ordered, she said quietly, "I have cancer," and tried not to laugh. The kid serving the ice cream either didn't hear her, or ignored her, unsure of what to do.As we walked away, I told her, "No, you have to say it and then come right out and ask for the sprinkles."

Card played unsuccessfully.

Gubar's point, though, is that sometimes we play cards with ourselves -- we use cancer as a way to make deals to do things we've wanted to do, or should do. Ice cream may very well be involved.

But we also need to recognize that everyone has a card, and they don't all have a C on them. If anything, cancer should put things in perspective. When you play that card, look around and see who else is sitting at the table. Take a look at their hands, too.

I'll do that. And when I lay down my cards, I'll keep smiling, Maybe even laugh sometimes.

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.

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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.

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.

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.

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.

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.

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.....

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.

Happy Thanksgiving

I'm aware that some Lympho Bob readers do not live in the United States. So as some of you may or may not know, today is Thanksgiving Day in the U.S.

It's a day set aside for us to give thanks, as the name implies. The cynical will say it's really a day to not go to work, eat 3 times the calories that a normal person needs in a day, watch football, and get mad at relatives. I might be leaving something out, but I think that about covers the basics. According to the cynical, anyway.

But many of us do take at least a few minutes to think about what we are thankful for.

Especially those of us who are cancer patients. Sometimes that can be tough -- it seems like there is so much bad stuff happening, it's hard to think about something good that's worth being thankful for. But even in the darkness, there's got to be a little bit of light. Or maybe even a little bit of hope? Look at the good stuff coming out of ASH this year (I haven't finished with that preview). Maybe it's dark, but at the very least, you can be thankful that somewhere, in one of those kitchen drawers, there's a flashlight. Don't give up looking for it.

For me, this year I am especially thankful for my family. I've been thinking about my lymphoma journey lately (I'm coning up on my 7th diagnosiversary in less than two months), and the part my family played. I've had lots of reason to think about them lately, and how important they have been to me.

My wife, of course, has always been a rock for me. We have a way of balancing each other out, being strong for one another when the other needs it. I'm very thankful for that.

And my kids. I have three teenagers now. They're good kids. not perfect, but very good. The things they give us to worry about are really not so bad. I don't brag about them here as much as I used to, but they're still doing lots of things worth bragging about.

And my father. He's always been a good model for me. I'm thankful that he's still here for me, helping whenever and however he can.

And my brother. When I was first diagnosed, he was there for me in so many ways. Things have calmed down over time, of course, and the heat and danger that comes with a cancer diagnosis has slowed and slipped away. But I still appreciate all that he did for me. I'm thankful that he was there, and I know if I ever need that again, he'll be there again.

And my nieces, my nephews, my in-laws, and the rest of my extended family -- I'm thankful for them, too. As we get older, and our lives get crazier, and there's more distance between us, it's easy to forget about them. But when I get the chance to be all nostalgic, I think about good times, and they make me happy.

I have lots of other things to be thankful for (including that upcoming diagnosiversary, and the 7 good years I've had since then), but this is a year to be thankful for family.

I hope all of you can take a little time to be thankful for something today. It's good to think about the good things.

ASH: Bendamustine + Zevalin

I think my ASH posts over the last couple of weeks have been kind of mixed. A couple of negative ones. I don't like writing those, but I think they're necessary. And I've avoided writing about some potentially positive ones that deal with new treatments, because I think those new treatments are kind of piling up, and I feel like I should hold off until we at least get to a phase II trial and have some evidence that they work. Overall, I think ASH this year is positive for Follicular Lymphoma. I'm just searching for the right news to show that it's true.

So here's a bit of good news: It looks like Bendamustine + Rituxan (B-R), followed by Zevalin, is a really good combination.

Bendamustine is, of course, a chenotherapy that seems to match CHOP in effectiveness, but with fewer side effects. That's a pretty nice combination. It seems to have replaced CHOP as an initial treatment for a lot of oncologists.

Zevalin, on the other hand, despite its effectiveness, is not nearly as popular. A type of RIT (RadioImmunoTherapy), Zevalin delivers a dose of radiation directly to lymphoma cells, unlike traditional radiation therapy, which needs a non-moving target. Studies have shown Zevalin and other RITs to be very effective. However, in the U.S., there are issues that keep it from being used as often as it might be (the way doctors who administer it get paid; the complexity of delivering a radiation treatment -- issues that are related to efficiency, rather than effectiveness).

It's too bad RIT is not used more often, given its effectiveness. I keep looking for new research that might be the incentive to say, "Damn to efficiency issues -- let's use it!" Maybe we'll get lucky with this ASH research.

Researchers from the U.S. wanted to see how well Zevalin worked after B-R for Follicular Lymphoma. Previous studies have looked at Zevalin as a consolidation therapy after R-CHOP. (Consolidation therapy means it was given right after a frontline treatment: R-CHOP, then Zevalin to kind of clean up anything left over.) Given how effective B-R has been for Follicular Lymphoma, it seems worth trying Zevalin with it.

And it was indeed worth it.

B-R was given to 38 patients. 22 of them received a Complete Response. 15 had a partial response. That's a 97% Response Rate (37 out of 38). The other one had stable disease. Still pretty good. Bendamustine + Rituxan is pretty darn good on its own.

Of those 38 patients, 30 were able to receive Zevalin as consolidation. 25 of them finished with a Complete Response, and 4 remain in Partial Response. Of the 14 who stayed in the study who had a Partial Response after Bendamustine, 7 of them moved to a Complete Response immediately after Zevalin. Three more achieved a Complete Response within 16 months.

So the final tally: 83% of the patients achieved a Complete Response. 96% achieved either a Complete or Partial Response. And 71% who had a Partial Response after B-R achieved a Complete Response after Zevalin.


That's pretty dang good.

I think what really stands out for me is that these numbers are achieved with treatments that are already available. I know I've written before about how I think chemo is slowly on its way out, and maybe some day we can all deal with Follicular Lymphoma with easier targeted treatments that disrupt pathways and control the disease. But I've also said that there is a role for chemo, and this certainly shows that it's true. Until we have treatments like Inhibitors that have been proven to work, we have B-R and RIT.

And with numbers like these, it certainly seems like a combo worth considering.

ASH: Stem Cell Transplants for Transformed Follicular Lymphoma?

More from the ASH preview: "Is Stem Cell Transplantation for Transformed Follicular Lymphoma Required in the Rituximab Era?"

As most of us know, Follicular Lymphoma sometimes transforms from a slow-growing indolent disease into a more aggressive lymphoma (often Diffuse Large B Cell). This happens to about 3% of FL patients every year, and the prognosis isn't good.

However, researchers from Royal Marsden Hospital in London say that much of what we know about Transformed Follicular Lymphoma comes from the pre-Rituxan Era, and doesn't consider the full effects of Rituxan on the disease. For example, in evaluating Transformed FL, patients who have had Rituxan Maintenance are often excluded from clinical trials. So they want to know what role Rituxan might play in Transformed FL, and whether or not Stem Cell Transplants (an aggressive treatment for an aggressive disease) are really necessary.

The researchers did a retrospective study, looking at records from Follicular Lymphoma patients from the past (2003 to 2013) who had transformed. They found 56 patients who fit the criteria.

The median time from diagnosis to transformation was just over 5 years. Of the 56 patients, 4 received an autologous Stem Cell Transplant (where stem cells come from the patient) and 2 received an allogeneic transplant, where a matched donor provides the stem cells.  50 patients received chemotherapy + Rituxan. Of those patients, 38 received R-CHOP, 13 recieved a different cho + Rituxan, and 9 received Involved Field Radiation Therapy (IFRT). 8 received Rituxan Maintenance after their post-transformation treatment. (There's some overlap with those numbers involving the IFRT and R-M.)

As for how well they did after treatment, measured by Overall Survival (OS) and Progression-Free Survival (PFS):
The R + chemo patients had a 2 year OS of 84.5% and PFS of 70.9%, and 5 year OS of 58.7% and PFS of 49.3%.
The R-CHOP patients had a 2 year OS of 89% and PFS of 76%, and 5 year OS of 59.5% and PFS of 51.7%.

But the patients who had R-Maintenance after their post-transplant treatment? They had a 2 year OS and PFS of 100%.

The researchers' conclusion: even the R-CHOP numbers are better than the numbers reported for Stem Cell Transplants, but the R-Maintenance numbers are clearly superior. They call for a closer look at using Rituxan Maintenance after treatments for patients who have transformed.

They are also very clear that their numbers are very small -- only 8 patients, and only after 2 years (not 5, as with the other treatments). So while it's very hopeful, it is a very small sample.

Transformation is a fear for many of us (if not all of us), and it's good to know there is another option being considered -- a fairly easy one that we already know something about.

ASH: Survival After One Year in Follicular Lymphoma

Interesting research from ASH on Overall Survival, one year after diagnosis: If things are quiet after one year, you're in pretty good shape.

Researchers wanted to know how important 12 Month Event Free Survival (EFS12) was in predicting Overall Survival (OS). In other words, if a Follicular Lymphoma patient went 12 months from diagnosis without needing treatment, having the disease behave more aggressively, or relapsing, would that be an indication that they had a better chance at longer Overall Survival? The quick answer is, yes, is does indicate that.

The researchers (from the Mayo Clinic and the University of Iowa) looked at 936 FL patients treated between 2002 and 2010, and then at another 153 from Lyon, France. They looked only at patients with grade 1, 2, or 3a Follicular Lymphoma -- no one with B symptoms, transformed lymphoma, or DLBCL. (That's important -- these tend to be the least aggressive stages of Follicular Lymphoma, though about 23% had other factors that made them "high risk" on a FLIPI scale.)

The results: Overall, patients with Follicular Lymphoma had a lower Overall Survival than the general population, no matter what stage they were diagnosed at. But patients who had an Event (progression of disease, relapse, need for treatment) within 12 months after diagnosis had a much lower Overall Survival.

This study is pretty interesting, but it requires a whole bunch of comments:

First, in a way, it isn't surprising: No events in 12 months indicates a fairly slow-growing variety of Follicular Lymphoma. For patients who maintain that slow growth (and I include myself), improved OS just makes sense. Assuming that slow growth stays.

Second, not everyone maintains that slow growth. As much as I'd love to think that things will always stay this way, I also know that there's no indication that slow growth at first means slow growth forever. Something like Transformation is unpredictable. It happens to people with more aggressive FL, and it happens to people who have gone years without treatment.

I think that's important to remember. Don't get cocky, Indolent Lymphoma People.

Third, this research looks at people who were diagnosed, in some cases, over 10 years ago. The world of Follicular Lymphoma is changing. The stats look at patients that were mostly treated with chemo + Rituxan, straight Rituxan, or Watch and Wait. Any of those approaches might be mostly off the table in a few years, given the pretty rapid development of targeted therapies like various inhibitors. There's the chance that those treatments change the game in huge ways, and that they halt the kind of aggressive disease growth that this research assumes is happening. No guarantees there, either, but it's worth remembering.

Fourth -- and maybe this is important enough that it should have been First -- statistics are numbers, not people. Particularly with such an unpredictable disease as Follicular Lymphoma, an Event within 12 months ultimately means nothing for an individual. This research describes trends, not guarantees. And they are historical trends at that -- stuff that happened to other people in the past.

We always look to what happened in the past, I know, when we're trying to predict the future. And really, that's mostly we have to go on. But this is a good reminder to keep the focus on what each of us has to deal with now, what is available to us now. No sense in worrying over what happened to someone else 10 years ago (or bragging about it, either.)

ASH: Ibrutinib Not So Effective for Follicular Lymphoma?

As I promised, I've been trying to make my way through the abstracts for the annual meeting of the American Society for Hematology (ASH). Lots of good stuff comes out at this meeting. Not necessarily stuff that can be used immediately, but good stuff to keep an eye on.

The first one I want to look at (kind of briefly, I'm afraid) is "Ibrutinib Monotherapy in Relapsed/Refractory Follicular Lymphoma (FL): Preliminary Results of a Phase 2 Consortium (P2C) Trial." It has some not-so-good news.

As the title suggests, this one reports the results of a phase 2 trial on Ibrutinib, a BTK inhibitor that has been approved for use in Mantle Cell Lymphoma and CLL. As a BTK inhibitor, Ibrutinib targets a particular enzyme that is necessary for a cell to function properly. In this case, it's a cancer cell. Inhibiting it, or blocking it from doing its job, means keeping the cancer cell from living.

The trial looked at 40 Follicular Lymphoma patients who had already had at least one chemotherapy treatment, and who were need of another treatment of some kind. (The link will take you a breakdown of age, gender, and previous treatments, if you're interested.)

The Overall Response Rate was 30%, but 65% showed some reduction in tumor size. Interestingly, only 2 out of 18 patients who were Rituxan-refractory (that is, Rituxan stopped working for them) showed a response, while 8 out of 19 who were still Rituxan-sensitive showed a response, as did 2/3 of patients who had never had Rituxan before.

So, overall, the numbers aren't great. Their conclusion says, "Single agent ibrutinib is well tolerated with a modest ORR in relapsed/refractory FL at this early assessment. Continued follow-up is warranted to capture late responders and to establish response duration.  Ibrutinib appears less active in FL than in MCL and CLL. Early PET scans (C1D8) do not reliably predict for response."

But I think there is some room in there for hope. The Rituxan connection seems like the best place to look, with some reason to think that straight Ibrutinib might not be so effective, but a combination with Rituxan might work better. (That seems to be a trend -- targeting multiple pathways with multiple agents, recognizing that sneaky cancer can find a way around just one.)

I'm also hopeful that, as they suggest, a longer follow-up might show some better results. This one was pretty quick -- about 6 months. They raise the possibility that Ibritunib might work over the long term.

So I wouldn't count out Ibrutinib as a treatment for Follicular Lymphoma just yet.  More to come, I'm sure.

ASH Abstracts 2014!

It's Blood Cancer Christmas Time again!

OK, that's a little sick, but when I see that the abstracts for the annual conference for the American Society of Hematology are available, I feel like a little kid on Christmas morning. The ASH conference is where some of the more cutting-edge research on blood cancers is presented every year. It's not necessarily research that can be put into practice immediately. In fact, it's more likely to be the first time that promising research gets presented to other experts in the field. But it's also at a stage where researchers are excited about sharing it with the world. So even if it isn't a big ol' stuffed Teddy Bear under the Cancer Christmas Tree, it's certainly a letter to Santa with all of the things we hope we'll get this year.

You can find the abstracts related to Follicular Lymphoma here. There are 191 of them, which is more than last year.

I've only done a quick scan of them, but it looks like maybe a few new focused treatments are being tested, there's some further testing of some established treatments, and a few surprises here and there. My plan is to look at and comment on some of these over the next few weeks -- the ones that excite me most.

I'll say it now, and say it again as I review things -- a lot of the stuff presented at ASH is in very early stages. It's stuff to keep an eye on for the (hopefully near) future, not necessarily stuff to ask your oncologist about when the subject of your next treatment comes up. But we can be hopeful,and excited about it anyway.

Stay tuned.

1000

This is my 1000th post to Lympho Bob.

I've seen it coming for a couple of months, and I've kind of had it in the back of my mind that I should do something special for it. I thought maybe it could match up with Thanksgiving, but the timing wasn't right. Would have been nice to be thankful in the 1000th post.

But, really, I am thankful, and I don't need a federal holiday to do it.

I'm thankful to all of you who read and comment and encourage me to keep writing.

If you've been reading for a while, or if you read some of the posts from the beginning, you know why I started this blog. Like so many of you, when I was diagnosed, I had no idea what I was dealing with. I heard CANCER and assumed the worst. Even for a few months, I still didn't quite grasp what an indolent cancer was, and why watching-and-waiting made sense, and what it all meant.

When I started, the blog became a way of letting people know what was happening. My wife and I know from experience, when someone we know and care about is sick, sometimes we're in a position to say, "How is it going? How are you feeling?" But we also know that sometimes, there are people that you care about, but that you aren't close enough to that you can call anytime and ask how they're doing.

So we decided that I would start this blog. It would be a way for people to know what was going on without wondering, "Is it OK if I call?" or hearing something from someone else who might have heard something about how I was doing and not getting the whole story. Basically, the blog would be a place for people to keep up without having to ask.

And it worked that way for a while. Friends and family visited regularly, and checked in on me, and made comments. And after a while, my doctor visits weren't so frequent, and I ran out of things to say about my lymphoma. And fewer of my friends and family read and commented.

Eventually, it became clear that I probably wasn't going to die any time soon, at least not from my indolent Follicular Lymphoma.

And eventually, my family and friends found other ways to gather together online. Which was fine. I was happy for the reason.

And every now and then, I'd get a comment from someone with Follicular Lymphoma who had somehow found the blog and who appreciated what they read. That was always nice.

And one time, someone who ran social media for a cancer drug company (I don't remember which one) started posting links to my posts on the company Facebook page and Twitter feed. That was pretty cool.

And then, somehow, more people found the blog. And I started to hear from more and more Follicular Lymphoma patients that they enjoyed reading what I'd written. And that was very cool.

Writers love to be read, and when I write on this blog, I always have readers in mind. But in the end, I write this for myself. If all of you went away (not that I want you to), I'd still keep writing. The blog gives me incentive to keep learning about my disease and what's being done to make it go away. I won't stop doing that -- I'll always be a Cancer Nerd. And every now and then, the blog is a place to express a frustration, or work through an idea. I won't stop doing that, either.

I don't know if I could have ever imagined, when I was first diagnosed, that the blog would last as long as it has, or that it would become what it has become. But I'm glad it has.

So I thank you all for reading. I promise I will continue to do my best to write about things that matter to Follicular Lymphoma patients, and I will do it as clearly and accurately as I can.

Expect another thousand posts -- at least.

Vaccines for Follicular Lymphoma

I've been swamped lately, folks. It's one of those busy times of the year at work, and I took on a project that  is taking way more time than I expected. Not to mention my oldest is applying to colleges now, and that's taking time and energy from all of us. I haven't even had time to respond to your comments, let alone write full posts. Ugh.

So here's a quickie so you know I'm still around:

A fast video from Targeted Oncology. Dr. Joshua Brody, Director of the Lymphoma Immunotherapy Program at Mt. Sinai Hospital, gives a quick take on Vaccines for Follicular Lymphoma. He points out that previous attempts at vaccines haven't been successful because they have targeted one Idiotype. Newer attempts take a more "holistic" approach, and target any antigens related to cancer cells.

The video is only about a minute long, but it gets at the pint that we shouldn't give up on vaccines -- they may be an important part of immunotherapy for us. (As I have mentioned before, the lymphoma specialist I saw soon after I was diagnosed was very excited about vaccines, and so they have always fascinated me.)

If you want to read a little more about Dr. Brody's work, check out another piece from Targeted Oncology, describing the results of a Phase I/II trial run by Dr. Brody, involving another immunotherapy treatment. To be honest, I read it but didn't look into it, so I while I get the overall idea of the approach, I don't know much about the parts.

But it's something else to be hopeful about.

(I'll get to those comments soon, I hope.....)

The "Fab Five" for Lymphoma

A few weeks ago, Medscape featured a video discussing some highlights from the 2014 Congress of the European Society for Medical Oncology (ESMO) in Madrid. The speaker is Dr. Martin Dreyling, professor of medicine at the University of Munich Hospital in Germany, and his focus is on recent developments in lymphoma.

The link will bring you to the video (it's about 12 minutes long) and a transcript (if you'd rather read his comments than watch).

In the video, Dr. Dreyling discusses the "Fab Five" (playing on the nickname for The Beatles, who were very popular in Germany before they came to the U.S.). But Dr. Dreyling is referring to the five compounds that are offering possible ways of avoiding chemotherapy for lymphoma patients (the unofficial theme of the ESMO conference). The Fab Five are: Bortezomib (Velcade), Ibrutinib, Idelalisib, Lenalidomide (Revlimid), and Temsirolimus (another kinase inhibitor, used for kidney cancer, now being tested for Mantle Cell Lymphoma). The Fabs, he says, "will help us."

Dr. Dreyling focuses on developments related to several specific lymphomas, including Follicular Lymphoma.He calls this section "Defying the Status Quo," by which he means moving beyond the current preferred approach in Europe, which is chemotherapy + Rituxan. Research shows that Follicular Lymphoma is sensitive to "targeted therapy," rather than the shotgun approach of chemotherapy. Idelalisib, for example, has been very effective (with over 50% response rates) for patients who have had chemo + Rituxan, but for whom that combination no longer works.

As an example of an approach that is used as a first-line treatment, he points to the RELEVANCE study, which involves Rituxan + Revlimid (R + R). The combination seems to work better than the two treatments given separately, and the RELEVANCE study involves over 1000 patients, very large even for a phase III trial. The response has been very good, and we'll know soon if it is as good, over time, as chemo + Rituxan.

The challenge for the next few years, as he sees it, will be to determine which of the Fabe Five compounds (and others like them) are working, but also what kind of markers will be found that will help identify which treatments will work best with which patients, and which will work best for all patients.

So while this wasn't a review of a lot of particular studies, I did find it valuable to see what is going on in Europe. I think they are dealing with a lot of the same challenges that we are dealing with in the U.S., and having some of the same successes.

And it's always fun to watch a lymphoma expert express optimism fore the future.

Ixazomib (Another Inhibitor)

The Blood Cancer Journal recently published the results of a phase I clinical study on Ixazomib, a proteasome inhibitor. It showed some promise for use on Follicular Lymphoma.

The article compares Ixazomib to Bortezomib (also known as Velcade), which was the first proteasome inhibitor to get approval. (It was approved for Mantle Cell Lymphoma, though some clinical trials for Follicular Lymphoma have looked good.) Bortezomib/Velcade works by blocking proteasomes, which help keeps cells healthy by getting rid of older and messed-up proteins. Protease inhibitors block that process in cancer cells, so all of those messed up proteins pile up in the cell and cause it to die.

Ixazomib will work in a similar way, though it has a different structure than Bortezomib/Velcade, which the developers hope will result in greater effectiveness and fewer side effects.

The phase I trial was meant to test whether or not it would work on certain types of lymphomas, to measure side effects, and to determine what the ideal dose would be. Of the 26 patients who went through the trial, 11 had Follicular Lymphoma, and 4 of them had a response. This is good enough to move on to a phase II trial.

The usual warnings apply here:

Phase I is very early. There will be a lot of time between now and when (and if) this gets approval, and clinical trial volunteers will be needed. It will also face the hurdle of needing to show it is better than what we have now, with Velcade. A response from 4 out of 11 FL patients is good, though not overwhelmingly good. We've seen a few  monoclonal antibodies try to outperform Rituxan, and so far no one has hit on the magic formula that will do that. Will the same thing happen with some of these attempts to improve various inhibitors?

We shall see.

Treatments for Follicular Lymphoma

You ask for it, you get it. That's how things work here at Lympho Bob. Satisfaction guaranteed or your money back.

A couple of weeks ago, an anonymous commenter asked:

Thank you for your blog! It has been really informative and helpful. I was diagnosed a month ago and reading your blogs has provided much insight into the medical and emotional aspects of this disease. I was wondering if you would consider doing an outline of the current treatment options available at this time. There is a lot of information out there and it can get confusing in terms of what the current options are. Thanks again! 

My response was to list a few, with the warning that I'd surely miss something, and to check the "Treatments" section at Lymphomation.org for more detail. I still think that's pretty good advice, but I also came across a piece in The Pharmaceutical Journal a couple of days ago that lays out current treatments for a few different types of lymphoma, including Follicular Lymphoma. It seems like the kind of list that the reader above was looking for.

But here are some warnings about the list:

First, it was published in a journal that is put out by the Royal Pharmaceutical Society. It refers to treatments that have been approved in the United Kingdom, not necessarily the United States. I think everything discussed here is also available in the US, but there may be some small differences in dosage, or in stage of treatment (frontline or refractory -- that is, some treatments are approved for patients as the first treatment they will have, while others are approved for patients who have already had certain types of treatments that stopped working).

Second, the author of the article gives his opinions about some of the treatments, and while he is objective about a lot of it, and gives links to specific articles in medical journals, he also throws some opinions in there, directly and indirectly. Goodness knows I don't have any objection to opinions, since I throw so many out there myself. But I think some commentary on some of what he says is necessary.

Third, it sounds to me like the person who wrote the comment above does not have an aggressive form of Follicular Lymphoma. A month in, and still considering treatment options? The oncologist must feel like there is some time to decide. I was in the same situation, and that colors the way I look at this article. Aggressive forms of Follicular Lymphoma require different decisions.

So here's some of what he has to say, with my commentary: 

•  “Common Chemotherapy Schedule for non-Hodgkin Lymphoma”

The author provides a nice chart with the treatment schedules for four different types of traditional chemotherapy with Rituxan. I’m not going to pretend to know if those are the same dosage schedules for the US. Honestly, I have no idea. But it is important to note that all four (R-CHOP, R-CVP, FCR, and R-Bendamustine) are available in the US, and are still used.  In fact, the commenter left the comment on a post I wrote about these chemos. So I don’t need to get more into my feelings about them, other than to say, I think they’re on their way out, especially the first three, and that’s a good thing. They still have a place in Follicular Lymphoma, but I think if an oncologist suggested one of them as a first treatment, I’d have a conversation about why, and why other options aren’t being considered.

• “R-bendamustine is increasingly being used as the combination schedule of choice.”

And if an oncologist is in favor of chemotherapy, R-Bendamustine would probably be the best choice of those four mentioned. The author acknowledges this, discussing how R-B has results as least as good as R-CHOP, but with less toxicity and fewer side effects. He also points out that Fludarabine (in the FCR combo) is no longer recommended in the latest European treatment guidelines, since it “has been found to increase rates of haematological toxicity” (which I think means it might give you a secondary cancer).

• Follicular lymphoma often presents asymptomatically and does not always require immediate treatment. Treatment is usually reserved until the patient becomes symptomatic, which occurs a median of 2.5 years after diagnosis, but can be more than 10 years.

 I think this is more or less true, though I would quibble over "treatment is usually reserved until the patient becomes symptomatic." That's describing watching-and-waiting, and I don't think it's accurate to say that W & W is the "usual" strategy. I think it's just the opposite, with maybe a quarter of patients holding off on treatment. Whether or not to begin treatment immediately, let alone which treatment to try, is still a big controversy in Follicular Lymphoma, at least in the US. I think that matters. Watching and waiting is a big decision, one that involves emotional and not just physical factors. It's a false impression to imply that most patients watch and wait until they show symptoms. 

• "Treatment with rituximab at diagnosis is currently being evaluated in clinical trials and, although it has yet to demonstrate an overall survival benefit, it does appear to improve progression-free survival rates."

And this is about all he has to say about Rituxan. I think it plays a much larger role in first-line or initial treatments for patients in the US, whether or not they have symptoms. It's an option, and a very valid option, for someone who is considering a first treatment. It's also such an important part of Follicular Lymphoma treatment (it's part of all of those chemotherapy options without ever being discussed) that maybe it's easy to take for granted and overlook. It should be overlooked.

• "Patients who present with limited disease can be treated with radiotherapy alone, which may cure the lymphoma."

Here, he's talking about stage 1 or stage 2 disease, something very limited and isolated, that can be treated with radiation, the way some solid cancer are treated. The problem is, only about 15% of Follicular Lymphoma patients are diagnosed at this early stage, since they are often without symptoms. 

And this is where I might talk about RIT -- RadioImmunoTherapy. Liquid cancers like FL, with that stage 1 exception, can't be treated with traditional radiation, since blood cells have a tendency to not keep still (since they are moving through the blood). RIT tracks down those cancer cells and brings a dose of radiation directly to them. It's a treatment that works for a lot of people, and for a lot of reasons is not used as much as it should be. This article is just further evidence that RIT is ignored.

• "It is unclear whether ASCT should be used in preference to rituximab maintenance therapy in follicular lymphoma. Younger, fitter patients may be considered for an allogeneic stem cell transplant using reduced intensity conditioning, as this is the only potentially curative option for this form of non-Hodgkin lymphoma."
  

And finally, he discusses Stem Cell Transplants. And again, this could use more space than it receives here. He refers to Allo Stem Cell Transplants, but there are also Auto SCTs, and both types are used for different purposes.

The article also includes some "future treatment options," including Ibrutinib and Idelalisib. There are even more than that, of course.

I don't think this is a bad article. It's not really meant as a definitive guide for patients, so it would unfair to criticize it for not being one. But I also think it's important to read carefully.

I'll give the same advice as before: for more information, Lymphomation.org is a good place to go. Lots of other websites give some basic infiormation about the different types, but, like this article here, you end up getting only part of a story. 

The best place to go for information is your oncologist. He or she is the one who knows you and your situation best.