Thursday, December 29, 2016

CR30: A New Way to Measure Effectiveness

While I've been looking at stuff from the ASH conference earlier this month, there's been even more research on Follicular Lymphoma that has been posted online. This one came out just yesterday in the Journal of Clinical Oncology: "Thirty-Month Complete Response as a Surrogate End Point in First-Line Follicular Lymphoma Therapy: An Individual Patient-Level Analysis of Multiple Randomized Trials."

If you follow clinical trials for Follicular Lymphoma, then you know that a couple of things are true: first, the best measure of a trial's success is Progression Free Survival (PFS). This is a measurement of how long the lymphoma takes to come back (if there was a Complete Response) or get worse (if there was a Partial Response). Overall Survival (measuring how long people live) would be great, but with an indolent lymphoma like FL, that's not a great measure of success. So we use PFS.

The second thing that is true is that PFS can go on for a long time. If a median PFS is necessary (that is, half of the patients in a trial have achieved a PFS), then the process can go on for a long time -- 6 or 8 years for some treatments.

That's great news for individual patients -- it means lots of us will have a long time before we need another treatment (I'm getting close to 7 years since my last Rituxan).

But it's not as good for us as as a group. A regulatory body (like the FDA in the U.S. or the EMA in Europe) might want to see a final PFS number before approving a treatment. That's a long time to wait.

The researchers in this study looked at a number of clinical trials conducted since 1990, involving over 3800 patients, and found that 30 months was a good substitute for median PFS. In other words, if the patients in a trial had a median PFS of 30 months, it was likely that the PFS would actually go on for some time.

Interestingly, they also tried to measure this with a 24 month time period, and found that it was not as accurate as the 30 month time.

It is important to note that this does NOT mean that an individual patient who has reached 30 months without needing treatment is not going to need treatment for a while after that. The number is not meant to predict individual patients' success with a treatment.

So what is it good for? Well, if agencies like the FDA and EMA accept it, it could mean that clinical trials could be shorter, and new treatments could become available to patients a little sooner. (One problem, though, is that looking at only the PFS rate means long-term side effects are not being measured, though I'm not sure how much that's taken into consideration anyway. Short-term side effects definitely are, but not necessarily long-term.)

So we can call this one "helpful down the road" -- we won't see the effects directly when we sit in the chair in a treatment room, but what they give us might be available to us because of it.

I'll look for something more exciting to report on next time.....

Sunday, December 25, 2016

Merry Christmas

Over the last couple of days, I was thinking about what I wanted to write today. And as I planned it out in my head, I noticed that it sounded familiar.

I checked what I wrote last year on Christmas, and it turned out, the message I was planning was pretty much what I wrote last year.

It was a wish for peace.

Today is Christmas, celebrated by much of the world (including me). And a traditional Christmas sentiment is "Peace on Earth." I'm going to wish for it again this year.

Last year, my wish was that all of us with cancer would have a little bit of peace for the day, and maybe pass that peace on to others we meet. Inner peace.

This year, I think I want peace beyond that. Outer peace.

It seems like we're living in a very divided world. People don't listen to the people who don't agree with them. Disagreement boils over into outright hatred. Last year was tough on a lot of people (whether or not they have cancer). Some days, I feel like the next year isn't going to be much better.

So my wish again is for peace.

Be patient. Be kind. Listen. Try to really understand one another. We all hurt in some way. Respect that in one another. Know that we all want the same things -- a healthy body, a job that gives us some dignity, to love and be loved. We might think differently about the way to get those things. But we all want them.

I don't know if I can connect this to cancer. Hatred is a cancer that spreads too easily? The outer turmoil of the world reflects our inner turmoil? We should listen to others the way we carefully watch and wait? I don't know. All of this goes beyond cancer.

So Peace to you all. Inner and Outer. Enjoy the day (whether you are celebrating Christmas, Chanukah, or just another day being alive), and stay healthy.

-- Bob

Image result for peace on earth

Sunday, December 18, 2016

ASH Review from Medscape

I plan to write about a few more interesting sessions from ASH that dealt with Follicular Lymphoma, but today I thought I'd let some experts do the talking.

Medscape asked two Hematology experts (Dr. Ann LaCasce and DR. Kerry Savage) to review the ASH meeting and talk about the things that they thought were significant. As the headline for the article indicates, sessions dealing with CAR-T were big news (we're going to keep seeing CAR-T news for a while, I think, as a treatment for Lymphoma and for a bunch of other cancers -- and it's only going to get more effective as time goes on and researchers learn more about how it works). But there were also a lot of "negative trials," where the outcome wasn't as good as researchers had hoped.

Of course, the big news for Follicular Lymphoma was the success of Obinutuzumab as an addition to chemotherapy (O-CHOP instead of R-CHOP, for example). Interestingly, Dr. Savage is not willing to call the study a game-changer, because there is still no data for Overall Survival, and Obinutuzumab might cost more and have more side effects that Rituxan. Time will tell how much of a change this study brings about for clinical oncologists (the folks we see at our regular appointments).

The link above will take you to a video of their conversation. They discuss lots of things from ASH, not just FL news. (And sometimes Medscape articles are hard to get to through a link, so if you can't access the article, I'm including a transcript below, which Medscape was kind enough to provide with the original article.)


Ann S. LaCasce, MD, MSc: Welcome to Medscape Oncology Insights. I am Ann LaCasce, associate professor of medicine at Harvard Medical School and senior physician at Dana-Farber Cancer Institute. Joining me today is Kerry Savage, associate professor at the University of British Columbia and a medical oncologist and clinical scientist at the BC Cancer Agency. We are at the American Society of Hematology (ASH) 2016 Annual Meeting in San Diego, where there have been a number of important lymphoma studies that we would like to highlight for you.
Kerry, what do you think is the most interesting abstract being presented at the meeting this year?
Kerry Savage, MD: It's tough. There were a few interesting phase 3 studies that came out, but for me, and I think for a lot of lymphoma specialists, we were waiting for the CALGB study comparing dose-adjusted EPOCH-R with R-CHOP.[1] This included newly diagnosed diffuse large B-cell lymphoma. Disappointingly, but probably not surprisingly, this was a negative study with equivalent event-free survival and more toxicity with the dose-adjusted EPOCH-R. We are eagerly awaiting the subgroup analyses to see if there are subsets that may benefit.
Dr LaCasce: Do you think the subset analyses will yield anything? For instance, in primary mediastinal lymphoma, where there seemed to be a signal that suggested that EPOCH is more effective.
Dr Savage: I'm hoping, but I'm not sure the numbers will be there since it's only about 6% of the whole population. But I certainly want to see those data. The one I am most interested in is the GCB cell-of-origin subtype from the previous phase 2 studies. It seems like that was the subtype that would benefit, given the proliferative drive as opposed to the antiapoptotic effect and NF-B pathways of activated B. I am hoping that we see some of that data, but it might come out at a future date.
Dr LaCasce: In terms of double-hit or double-protein expressors, maybe we will get some information on that.
Dr Savage: Again, I think the double-hit might be too infrequent, at 5%. For the dual expressor, I am not holding my breath for that because most are activated B, and that is not the group that I think will see the benefit. For me, that is the talk I want to hear the most, even though it is a negative study. It is a really important study.
Dr LaCasce: What about the GOYA study[2] with obinutuzumab?
Dr Savage: The GOYA study was on newly diagnosed diffuse large B-cell lymphoma, but this time comparing R-CHOP with obinutuzumab (GA101). Again, it was a negative study. There seemed to be no benefit from the addition of obinutuzumab. There is, in the abstract, a suggestion that perhaps there might be a benefit in the GCB subtype, so we will be looking to see that. It's disappointing that we haven't seen the benefits of these additional agents in diffuse large B-cell lymphoma.
Dr LaCasce: In terms of the toxicity of that antibody, do you think the signal was impressive or not that important?
Dr Savage: I think it's important. We see a lot of infusion-related reactions with obinutuzumab as well as additional infection and neutropenia.
Dr LaCasce: In terms of obinutuzumab and follicular lymphoma, the plenary, we had a big study looking at obinutuzumab versus rituximab in upfront follicular lymphoma.[3] Do you think this will change practice?
Dr Savage: It's an interesting study. As a reminder, it was a study comparing any chemotherapy backbone—it could have been CVP, CHOP, or bendamustine with rituximab—with the same chemotherapy backbone and obinutuzumab. That was actually a positive study, which is why it's in the plenary session for progression-free survival. If you look at the curves, the absolute benefit is still quite small. It is only about 4%-5%. And again, we have the additional toxicity that we already talked about, such as infusion-related neutropenia and infection. And, of course, there is cost on top of that. Given that this is a chronic disease, we still don't know about overall survival. I am not sure how that's going to follow in terms of being practice-changing.
Dr LaCasce: In terms of maintenance, do you think it impacts how you assess the results of the study?
Dr Savage: Potentially, although both arms got maintenance.
Dr LaCasce: There was a hint of more secondary malignancies. Do you think that's real? It was a large randomized study.
Dr Savage: It's interesting. I am wondering if that will come out when we hear the discussion. There are double the number of secondary malignancies, but they are still low overall (6% versus 3%-4%), and it is early to be seeing that. I think we need more details. I would like to know if those are all solid tumors or if there could be some transformation events. That is something we will have to watch for and probably see some more mature follow-up.
Dr LaCasce: Mechanistically, it does not make sense. Something that everyone is looking forward to is seeing some more data on CAR T cells. What do you think about the late-breaking abstract on diffuse large B-cell lymphoma[4] and the other abstract looking at transformed follicular and mediastinal lymphoma?[5]
Dr Savage: It's exciting. These are patients who do not have any other options, and we have seen excellent efficacy in T-cell acute lymphoblastic leukemia (TALL). Now we are seeing this therapy spill into the lymphoma world. I'm very interested in the late-breaking abstract looking at a fairly large dataset of relapsed/refractory diffuse large B-cell lymphoma with CAR T-cell therapy.[4] The CR rate is almost 50%. The duration of follow-up is still short. I think they are only looking at 1 and 3 months. So, the big question is: How durable are these responses? Considering how heavily pretreated this population is, these are very encouraging results. Similar findings were in the transformed and primary mediastinal population as well. Again, a difficult-to-treat population.
Dr LaCasce: Maybe a hint that they may respond a little bit better. What about the toxicity?
Dr Savage: Always the flip side. The cytokine release syndrome is worrisome. This can only be given in specialized centers that are attached to ICUs. Also, the signal of neurotoxicity still raises concerns. Can we strike that balance of efficacy and toxicity? We will have to see more data on that.
Dr LaCasce: Yes, it will be interesting to see how that's scaled up and taken to a much broader group of patients. What about mantle cell lymphoma? The maintenance rituximab after autotransplant[6]—those data were compelling. Do you think that will change practice?
Dr Savage: I think it could. Some people are probably already using rituximab in the maintenance setting. This was a well-designed phase 3 study showing a benefit in progression-free survival with the addition of maintenance rituximab.[6] It was quite a significant difference in the progression-free survival—about 20%. Rituximab was given every 2 months for 3 years. It's a little bit different from other settings. Whether you need it for that long, I don't know, but it could potentially be practice-changing. It was a well-conducted study.
Dr LaCasce: It looked like the toxicity was not that different between the two arms. What about Hodgkin's lymphoma? We are going to see some data in the first relapse setting combining brentuximab and nivolumab.[7] What do you think about those data?
Dr Savage: It's interesting. The data we have seen so far with the checkpoint inhibitors have all been in patients post-transplant, or there have not been a lot pre-transplant. The design of this trial was to function as a salvage regimen as a lead-in to transplants: brentuximab vedotin and nivolumab, a phase 1/2 study, and four cycles. The response rate is very high at 92%, with a CR rate of about 60%. It is higher than what you would expect with nivolumab and a little bit better than what you would expect with brentuximab. There is certainly some rationale to combining them, and there is synergy. Brentuximab is immunogenic. Of course, we need to see longer-term follow-up and the progression-free survival, but I think we are going to be seeing more studies like this in that setting in Hodgkin's lymphoma.
Dr LaCasce: As we are seeing more patients getting brentuximab earlier, and maybe with the results of the randomized study, how are we going to move this forward?
Dr Savage: It's difficult. Depending on how ECHELON-1, the phase 3 upfront study, reads out, the rules are all going to change. Is the efficacy going to be as good? We have some data to support that brentuximab in the re-treatment setting works. I think the limitation will be peripheral neuropathy and the toxicity associated with it. We will need more data to know whether the landscape is going to change if brentuximab becomes incorporated into frontline therapy.
Dr LaCasce: Do you think there will still be a role for autologous transplants if we have these combination studies that have high complete remission rates?
Dr Savage: I have to admit that I'm still on that. I would not want to deny a transplant. We have such good data that transplants are curable. The stakes are high in this young population. Would you be willing to do a trial that does not do transplant? You'd really have to think carefully about how to design that trial and the patient population.
Dr LaCasce: It seems like there aren't really any interventions that have changed overall survival, so maybe it would be open to study.
Last, in cutaneous T-cell lymphoma, there was a randomized study comparing brentuximab with investigator choice.[8] How do you interpret that study?
Dr Savage: That was an interesting study. Patients had to have had one prior therapy, and then they were randomized to either brentuximab or investigator's choice of methotrexate or bexarotene. There was a striking difference in outcome. They had an interesting primary endpoint. It was ORR4, which means overall response rate sustained for 4 months. It was significantly better in the brentuximab arm, at about 56%. Looking at the conventional response rate, it was hitting around 60%. There was a striking difference in median progression-free survival of almost 1.5 years versus about 3-4 months. This is definitely practice-changing. This is a difficult-to-treat population. It is difficult to assess response, but they did their best to use this global score to assess response. The data are quite compelling that we are going to see brentuximab used in this setting.
Dr LaCasce: Thank you, Kerry, for joining me for a very interesting discussion, and thank you for joining us both for this edition of Medscape Oncology Insights. This is Ann LaCasce with Kerry Savage, reporting from ASH 2016.

Wednesday, December 14, 2016

ASH: More on Zevalin

OK, back to ASH abstracts.

There is a lot of great stuff from ASH this year. I think I've covered the ones that have made big news, but there is still a lot that, to me, is worth looking at.

I already write about a new possible RadioImmunoTherapy (RIT) treatment that was discussed at ASH, and how that was good because RIT is shown to be very effective but is very underused in the U.S. We may lose Zevalin forever.

And yet, at ASH, there were two presentations that had very positive things to to say about Zevalin.

The first is called "90Yttrium-Ibritumomab Tiuxetan as First Line Treatment for Follicular Non-Hodgkin Lymphoma. 5 Year Results from an International Multicenter Phase II Clinical Trial." In the U.S., Zevalin is approved for use on patients who have already had treatment, and whose condition has gotten worse enough that they need treatment again. This study reports on a clinical trial (of European patients, from what I can tell) who had Zevalin as a first treatment. The trial involved 59 patients with Follicular Lymphoma of different stages. 

After 6 months, 56% of the patients had achieved a Complete Response, and 31% had achieved a Partial Response (for a 87% Overall Response Rate). Pretty good. After 1 year, 26 of the 39 patients who had a Complete Response had not had their disease return. Of those 26, 57% had still not seen their disease return after 5 years (a 40% Progression Free Survival). Overall Survival for the whole group after 5 years was 80%. Most side effects were well-tolerated.

The researchers conclude that Zevalin is effective, safe, and useful as a first-line treatment.

In another study ("Short Course of Bendamustine and Rituximab Followed By 90Y-Ibritumomab Tiuxetan in Patients with Chemotherapy-Naive Follicular Lymphoma (FOL-BRITe): Final Report of Response Rates and Progression Free Survival"), Zevalin was given to patients after they had 4 rounds of Bendamustine + Rituxan. Early research on Zevalin as a consolidation treatment (that is, used right after a first treatment as a way of cleaning up any leftover cancer) lokked at Zevalin after R-CHOP. Since B-R is seen as even better than R-CHOP, it makes sense to see if following B-R up with Zevalin is even better than it would be following R-CHOP.

The study involved 39 patients. After receiving the Bendamustibe, 22 of them had a CR, and 16 had a PR, so the Overall Response rate was 97%.  Of those 16 with a PR, 10 had a Complete Response after they received Zevalin.

After a median follow up of 30 months, 71% did not have their disease return. Side effects were well-tolerated.

So, both studies continue to show that Zevalin works well, lasts for a while for a lot of patients, is safe, and should remain an option for Follicular Lymphoma patients.

Now there are some other people who need to be convinced of that.......

Saturday, December 10, 2016

A Reminder about Being Positive

We're taking a short break from ASH proposals today.

I saw this blog post ("Can I Please be Allowed to Have Bad Days After Cancer?") on my Facebook wall yesterday, and I thought it was a good time to bring up the idea of positivity. I like to come off as very upbeat and hopeful when I write on Lympho Bob, and I think people who know me will agree that I'm like that offline, too. I tend to look on the bright side.

But I have my rough days, and frustrating days, and downright sad days sometimes. When you're as upbeat as I am, people tend to notice when you're even a little bit down. I had one of those sad, heavy days about a week ago. It wasn't something cancer-related, but it did weigh on me very heavily.

The blog post that I linked to is from a survivor of Acute Myeloid Leukemia, and while she seems to have made her way through it, she still finds herself feeling very sad some days, and then guilty for feeling sad; she's a survivor, after all -- what is there to be sad about?

I think we all get that way as cancer survivors (and we're all survivors, even if we're still in treatment, or watching and waiting, or just feeling horrible -- we were diagnosed, and we're still here, so we're survivors).

For those of us with Follicular Lymphoma, the feelings might be a little different. We're told we have an incurable disease, so even if we are cancer-free, we can never quite be sure about it. Even though it's been almost 7 years since my last treatment, I still worry. After my Rituxan, I was told I had a Partial Response, so there was a little cancer left. Same with my last scan a couple of years ago -- not completely clean. I don't have those same feelings of guilt as the woman who wrote the blog post, but I still feel that sadness sometimes. And for some of us, that does come with a similar kind of guilt. We're survivors, too, aren't we? Unlike some cancer patients, we have a shot at a long Overall Survival. How many of us have been told we have "the good kind" of blood cancer? How many of us have been told, "If you have to get cancer, this is the one to get"?

So why should we feel sad about having cancer?

My point is this -- it's OK to feel sad. It's OK to have a bad day.

There's an idea in the cancer community called "The Tyranny of Positive Thinking." (It comes from a book by Dr. Jimmie Holland called The Human Side of Cancer, and I first saw it posted in my online support group.)

The idea stems from the that, as cancer patients, we should always be positive, and that any negative feelings might actually make our cancer worse. People tell us this all the time -- "Hang in there! Stay positive! It's the only way you'll get better!" I think it's one of those things that people say when they don't know what else to say, and it's a message that cancer patients are constantly getting from others. Now, a positive attitude can be an excellent thing. But it can be a burden, too. Because if we're having a down day, and we're being told to stay positive, and we just don't feel like it, we now have the burden of feeling guilty, too. Double the negative emotion with none of the good results. (And on top of that, there is no scientific evidence that feeling negative thoughts hurts you.)

As I said, I like to stay positive in the blog, and I do my best to focus on things that are hopeful. I hope I'm not contributing to anyone feeling guilty about being down.

But if I do, here's the big message here:

It's OK to feel sad sometimes.

You've been diagnosed with what everyone keeps telling you is an incurable cancer. You might have kids, or a spouse, or family and friends that rely on you. You might have big plans that have been shoved aside. Why wouldn't you feel sad some days?

So if you're having a bad day, you have my permission to not smile. Have your bad day. Call in sick to work. Go back to bed and watch sad movies all day and eat ice cream for lunch. Let your dog up on the couch with you. Tell someone to bring you something that's bad for you. Put your head under the blanket and stay there. Scream into your pillow. Be short and nasty to anyone who talks to you.

Have a bad day. You deserve it.

And if tomorrow is bad, stay in bed then, too.

But here's the thing -- if you feel this way three days in a row, get some help. Talk to someone. Put down the ice cream and call your doctor and see if there's a professional who can assist you.

Depression is a real thing for cancer patients, especially newly diagnosed ones. A sad day or two is OK. But a sad life is one that needs some help.

Thanks for listening. I hope your days are happy.

(I can't help myself....)

(Back to more of that positive stuff from ASH.)

Wednesday, December 7, 2016

ASH: Another Possible Rituxan Replacement

The ASH Conference is now actually over (it ended Monday), but I still have lots of Follicular Lymphoma news to go through. We're starting to see lots of folks bragging about their presentations, which is great. There was a lot of stuff worth bragging about this year.

It seems like one of the really big winners of this conference was Obinutuzumab, which I wrote about a few weeks ago. It is a potential replacement for Rituxan -- it operates in much the same way, but may be even more effective because of the way it was created. (Of course, the really really big winners are those of us with Follicular Lymphoma....)

Rituxan has been a huge part of why Follicular Lymphoma survival rates have been increasing in the last 20 years or so, and there have been a bunch of attempts to find a monoclonal antibody that can improve on Rituxan. So far, no one has been able to find one. Until now. I don't think Obinutuzumab will replace Rituxan completely (oncologists' habits are hard to break), but it might chip away at its dominance.

Combine that with another presentation from ASH, and we might very well see a lot less Rituxan soon.

Rituxan's patents have expired (in 2013 in Europe and a few months ago in the U.S.). That means generic or biosimilar versions can be sold. Biosimilars are basically copies of the already-used treatment (in this case, Rituxan). If they are developed properly, they will be as effective as the original, with the same kinds of side effects. They will also likely be cheaper, since pharmaceutical companies use a lot of their profits to help recoup their costs for research and marketing of their products. A generic or biosimilar has a head start -- people already know it works as well as Rituxan.

Of course, that assumes that it does work.

The ASH presentation called "A Phase III Efficacy and Safety Study of the Proposed Rituximab Biosimilar GP2013 Versus Rituximab in Patients with Previously Untreated Advanced Follicular Lymphoma" set out to show that a biosimilar can indeed work as well as Rituxan.

The researchers tested a biosimilar called GP2013. The study looked at 629 patients in 26 counties. Half were given the chemotherapy CVP + GP2013, and then 2 years of maintenance with GP2013. The other group was given CVP + Rituxan, plus 2 years of Rituxan maintenance.

The Overall Response Rate for the GP2013 group was 87.1%. For the Rituxan group, it was 87.5%. That's a very small difference -- enough to say that the biosimilar is indeed similar to the original. The researchers also tried to measure median Progression-Free Survival and Overall Survival, but the median had not been reached after 3 years (that is, less than half of the group had progressed or died, so they couldn't measure it).

Both groups also had similar side effects.

There are actually quite a few Rituxan biosimilars being developed. I'm still not willing to say they will replace Rituxan completely, but it's good to know there are some out there. Cost is a factor for everyone, if something can give the same results for a lower price, we all benefit.

The only thing left for GP2013 to do is come up with a better name. They definitely need something snappier -- ideally, with an X or a Z in it. Or more than one. My suggestion? "Rituxisimilex." (If you're reading, dear researchers, you're welcome to use that name. No charge. Just keep doing what you're doing.)

Thursday, December 1, 2016

ASH: A New RadioImmunoTherapy Treatment?

In the U.S., we're dealing with a sad decline in the use of RadioImmunoTherapy (RIT). Bexxar is no longer available to patients, and Zevalin is being made difficult to use because of unreasonable government regulations.

But that doesn't mean RIT is dead yet (we need to keep fighting for it in the U.S., people).

More importantly, there's another RIT treatment in early clinical trials in Europe, and results are bing reported at ASH.

The treatment is called Betalutin, and the ASH report is called "177lu-Satetraxetan-Lilotomab in the Treatment of Patients with Indolent Non-Hodgkin B-Cell Lymphoma (NHL), Phase 1/2 Safety and Efficacy Data from Four Different Pre-Dosing Regimens."

Like other RIT treatments, this one involves attaching a small amount of radiation to  monoclonal antibody that targets a protein on lymphoma cells. Zevalin, for example targets the protein CD20. The new RIT treatment, Betalutin, targets a different protein, CD37.

Many of the same researchers from the ASH study reported in Blood journal a couple of years ago that Betlutin seemed safe, with manageable side effects. I assume the ASH results are from the same trial, or a related one, given the overlap in researchers, but I don't know that for sure. Whatever the case, the ASH presentation gives a more detailed look at the results.

They describe this as a phase 1/phase 2 trial, so it's fairly small -- 36 patients enrolled, 23 able to evaluated, and 20 of those 24 had Follicular Lymphoma. Patients were divided into 4 groups. Because it's an early trial, part of the goal is to see which is the most effective way of giving the treatment, each of those 4 groups was given the Betalutin in a slightly different way. All of them were given a dose of Rituxan first, and then they were given some combination of Rituxan and/or Lilotomab (an anti-CD37 monoclonal antibody), and then Betalutin.

Patients were given a PET/CT scan at 3 months and 6 months after they finished treatment, and then after 5 years. There were some side effects, but no deaths and so secondary cancers as a result of the treatment.

The results were pretty good. The Overall Response rate was 57% (7 Complete Responses and 6 Partial Responses). 5 patients has stable disease, which left 5 whose disease got worse.

The researchers' conclusion: "Betalutin has the potential to be a novel, safe and effective therapy for B-cell malignancies with durable responses. Betalutin, a single dose, ready-to-use formulation, has a predictable and manageable safety profile which is improved by pre-dosing. Most AEs were haematological, all transient and reversible."

RIT works. That's all there is to say. I hope Betalutin proves to be effective in future, larger trials, and it helps you folks in Europe. As for us in the U.S., I hope this type of treatment doesn't go away. We have lots of arrows in our quiver, and I'd hate to see us lose even one -- especially one that has done so much good for so many people.

Sunday, November 27, 2016

ASH: Vitamin D and Follicular Lymphoma

Another interesting ASH presentation -- this one is called "Vitamin D Insufficiency Is Associated with an Increased Risk of Early Clinical Failure in Follicular Lymphoma."

I'm very interested in Vitamin D and FL, mostly because I take some every day, on the advice of my doctor. It's kind of a controversial supplement, in that some doctors get very excited about patients taking it, and others are more skeptical, and there are lots of studies that suggest it's a problem not to have enough, and others that aren't quite so sure.

For me, despite my mom's Italian heritage, I'm mostly of fair-skinned Scottish-Canadian ancestry, so I try to stay out of the sun. And that means my body isn't making Vitamin D naturally, so I take a supplement.

Before I go any further, let me be clear: I'm not suggesting that anyone else should take Vitamin D. That's my choice, based on my doctor's advice. You should talk to your own doctor about whether it's a good idea for you.

Also, I'm NOT suggesting that there is any research that says Vitamin D will cure your Follicular Lymphoma. It's easy to get excited about these kinds of potentially easy solutions, but nothing is easy with Follicular Lymphoma, as we all know.

So, on to the study:

Researchers looked at 642 newly-diagnosed FL patients. They wanted to figure out if low Vitamin D levels in the blood could predict if a patient would have early clinical failure (measured by Event-Free Survival at 12 months, or EFS12) and Overall Survival, as well Lymphoma-Specific Survival (death caused by Lymphoma and not something else). They were interested to see if low Vitamin D levels were related to how successful specific treatments were, too.

They found that in the entire group, low Vitamin D levels were associated with inferior EFS12, OS, and LSS -- all three.

The same was true of patients who had Immunochemotherapy (something like R-CHOP or R-B) -- inferior for EFS12, OS, and LSS.

For patients who were observed (watch and wait), low Vitamin D was associated with low Overall Survival, but there was not enough of a connection to say it was associated with EFS12 or LSS.

There were not enough events or deaths to measure any connections for patients who had straight Rituxan. (That's bad for the study, but good overall.)

Their conclusion: "We confirm previous findings that vitamin D insufficiency is associated with adverse long-term prognosis among patients with FL treated with IC, and extend these findings to patients who are initially observed or treated with other therapies.  For the first time, we observed an association of vitamin D insufficiency with early clinical failure, suggesting a potentially modifiable factor to address in this subset of patients with poor outcomes.  Whether treating VDI improves outcomes in FL warrants assessment."

In other words, having low Vitamin D levels can make things worse for you. But that doesn't mean having sufficient or high levels will make things better.

So, it's an interesting study with no firm conclusions, other than to talk to your doctor about whether your Vitamin D levels are OK, and whether or not it matters.


Monday, November 21, 2016

ASH: A New Way to Think about Watching and Waiting

I'm fascinated by studies that ask whether or not Watching and Waiting is worth it for Follicular Lymphoma patients, even though they drive me crazy. It seems like these studies go back and forth with one another -- one will provide some evidence that Watching and Waiting is a better choice than being treated right away, and then a few months later, another study will say the opposite.

I don't think there is any right answer, but I keep reading them anyway, mostly because I want someone to tell me I was right to hold off on treatment for two years.

(Really, I don't need anyone to tell me I was right. I'm coming up on my 9 year diagnosiversary, and I'm still here. That's about as right as it gets. But I'd still like that decision to backed up by science, if that's possible.)

Since there doesn't seem to be any right answer to this question, I was pretty thrilled to see an ASH proposal that asked a different question: is there a better way to measure whether or not Watching and Waiting is an effective strategy?

The session is called "Intervention Versus Observation: What Is the Appropriate Endpoint? Assessment of Endpoints in Patients with Advanced Stage Follicular Lymphoma Who Are Initially Observed." Most research that compares the two options (watching and waiting vs. treating right away) by comparing Progression Free Survival or Time to First Next Treatment, these researchers suggest a better way to measure is Time to 2nd Treatment (TT2T).

Here's the logic: Imagine a trial that involves half of patients watching and waiting, and then measuring how long it takes to get to their first treatment. The other half involves patients getting Rituxan, and then measures how long it takes for them to get to their next treatment. Those two times are compared to see which approach works better.

But this is an unfair comparison. One group is measured by how long it takes to receive their first treatment, and the other is measured by how long it takes to receive their second treatment. What if we looked at that first (W & W) group and measured how long it took them to get to a second treatment?

More importantly, could TT2T be a replacement for measuring Overall Survival? In other words, studies that use that first treatment as a way of measuring success might be stopping their measurement too early. The big question with FL treatments is always "Dies this treatment improve Overall Survival (OS)?" Does TT2T give us a better idea (since it is measured over a longer period) of how well W & W might contribute to Overall Survival?

The answer, they say, is Yes. In a study of 264 FL patients, with a median follow up of almost 11 years, they found that the Time to First Treatment was 43.5 months -- just under 4 years. But the median Time to 2nd Treatment (TT2T) was 151.8 months -- almost 13 years. Median Overall Survival was not reached, so it will be more than 13 years. So the TT2T would seem to be a better measure of Overall Survival when comparing W & W with initial treatment.

The researchers think there needs to be more research before TT2T can be a replacement for OS, and I think there's some value on figuring out whether it can be (Overall Survival measures death by any cause at all, from cancer to heart attack to getting hit by a bus, while TT2T focuses only on how whether the lymphoma has progressed enough that treatment is necessary).

I like the statistics presented, too: 8 or 9 years is a long time between the first and second treatment, and it roughly follows the path that I seem to be on (2 years until first treatment, and almost seven years since and I still haven't needed a second one yet). My first treatment came exactly two years to the day from my diagnosis -- shouldn't that put me in that high risk group that needs treatment within 24 months? But my (not yet needed) second treatment puts me a very different group, one that has a slower-growing for of FL, and seemingly lower risk.

Mostly, I like that this gives us a different way to think about Watching and Waiting, and whether it is worth recommending as a strategy. In the end, that's an individual choice, one that involves an emotional assessment, and not just a scientific one. But it's ncie to have something else to add to the conversation.

I still feel like I made the right choice -- for me.

Before I go, a note about terminology: The researchers use the term "Observation" instead of"Watching and Waiting." I had someone comment a while ago suggesting we stop using the "and waiting" part of that, and just call it "Watching" -- essentially the same thing as "Observation" -- because the "waiting" part brings on unnecessary stress. I use the "W & W" term mostly because it's the term I've been using for almost 9 years, and switching might be confusing to some people. I also think the "and waiting" is kind of unavoidable. We don't just watch -- we expect something to happen. I certainly did. So I respect the idea of going by a different term for a very good reason, but I'm sticking with W & W. It's a more accurate reflection of own experience.

Friday, November 18, 2016

ASH: R-Squared

More exciting news from ASH. The focus in in R-Squared, Rituxan + Revlimid (also known as Lenalidomide).

Researchers from Switzerland and the Nordic Lymphoma Group have been looking for a while at R-squared as a first treatment for Follicular Lymphoma. They reported positive results of a trial that looked at R-Squared's effect on Response, and found that it had a higher Complete Response rate than Rituxan alone, with manageable toxicity (basically, the side effects were outweighed by the results). They reported those results in articles in Blood and Hematological Oncology (sorry -- can't get a link working for that one).

The ASH presentation is a follow-up on those early results, and is called "Rituximab Plus Lenalidomide Versus Rituximab Monotherapy in Untreated Follicular Lymphoma Patients in Need of Therapy. First Analysis of Survival Endpoints of the Randomized Phase-2 Trial SAKK 35/10."

Basically, they knew that R-Squared worked really well after 23 weeks (measuring for the percentage of patients who achieved a Complete Response). Now they want to know, is it effective beyond that point? Do those responses hold over time?

The answer is, Yes.

They used several different measures to figure this out. Half of the patients were given Rituxan alone, and half were give R-Squared.

The R-Squared patients had a better Complete Response duration; after 3 years, the median hadn't been reached, while it had been after 2.3 years for the Rituxan group.

The R-Squared patients had a better Progression Free Survival (the time it took for the lymphoma to get worse); after 3 years, the median hadn't been reached, while it had been after 2.3 years for the Rituxan group.

The R-Squared patients had a better Time To Next Treatment; after 3 years, the median hadn't been reached, while it had been after 2.1 years for the Rituxan group.

Overall Survival was great for both groups (93% for R-Squared and 92% for Rituxan only).

Lots of specialists are excited about R-Squared, and this study seems to give them more to be excited about. Interestingly, these results come from a phase 2 study. A phase 3 will involve a larger group of patients, and results will likely lead to the combination being approved as a first treatment for FL patients. That's always good news.

Tuesday, November 15, 2016


More from the ASH abstracts.

This one has kind of a retro feel to it: "Sequential RCHOP, Radioimmunotherapy and Rituximab Maintenance Improves Early Outcomes in Advanced Stage Follicular Lymphoma: 5 Year Outcomes from SWOG 080."

This involves a Phase II clinical study involving 84 patients (at first) with stage 3 or 4 Follicular Lymphoma (or bulky stage 2), who have not yet had any treatment. Patients were first given six rounds of R-CHOP (Rituxan plus the chemo combo CHOP), then followed up with Zevalin (the RadioImmunoTherapy treatment), and then given Rituxan Maintenance for 4 years (once every 3 months).

Before I get to results, a couple of comments. As I said, this one has kind of a "retro feel" to it. Let me explain.

First, all of the big news these days focuses on treatments that are moving away from traditional chemotherapy like CHOP (and CHOP is about as traditional as it gets for Follicular Lymphoma). So it's interesting to see a successful trial involving chemo (and, as you'll see, it was successful). I've certainly expressed the opinion that CHOP trials are kind of outdated, and that resources could be better devoted to other things. But I've also said that CHOP still has a place in our bunch of treatments, and we certainly shouldn't get rid of it. (I'll say one or the other depending on my mood -- I'm fickle that way.) This trial also feels kind of retro because it involves RIT, which might be on its way out as an available treatment.

And finally, it feels kind of retro because I remember getting very excited, years ago, about a study that looked at R-CHOP and RIT (no maintenance) that was successful, and the researchers thought it was successful because the lymphoma was being attacked in 3 different ways. That combination approach always made sense to me -- cancer is too tricky to expect one treatment to wipe it out.

And this particular combination worked pretty dang well.

84 patients went through the R-CHOP and RIT. 59 of them had a Complete Response and 23 had a Partial Response, for an Overall Response Rate of 99%.

69 of those patients went through the last step and had Rituxan Maintenance, with 42 completing the full 4 years. The Overall Survival after 3 years is 96%, and after 5 years it's 94%.

Patients at various points in the trial experienced a variety of side effects, as they detail in the abstract. They had the most patients drop out of the trial during the Maintenance phase; they think 4 years is just too much time to be taking Rituxan.

But overall, those are some pretty good numbers. The researchers think this approach (RCHOP + RIT) could work well with "precision strategies" (which I assume are things like pathway inhibitors and immunotherapy), as a way of halting more high-risk lymphoma early on, with (I am guessing) those precision strategies to manage it from there.

So here's to retro treatments -- they still have a lot to offer us. Maybe this could be one of the many studies that show that RIT is worth saving?

Friday, November 11, 2016

ASH: Obinutuzumab (Two Studies)

Continuing with ASH commentary:

There are two sessions that will present results from the GALLIUM study, which looked at Obinutuzumab (also known as GA101 and Gazyva) plus chemotherapy as a first treatment for indolent lymphoma patients, comparing it to Rituxan + chemo.

Obinutuzumabis an anti-CD20 monoclonal antibody, like Rituxan. But it has been created differently. First, it is humanized, meaning it is created from  human cells (Rituxan has some mouse parts in it  -- sorry, some murine components). Some think humanized anibodies will cut down on the allergic reactions that Rituxan sometimes brings on (as it did for me). Obinutuzumabis also glycoengineered. Basically, it was made to have more sugar-related enzymes, which allows it to signal some T cells that will find and kill the cancer cells. There's more to it than that, but the bottom line is, Obinutuzumabwas created so it would be like Rituxan, but more effective.

The two studies from ASH focus on Follicular Lymphoma patients from the GALLIUM study (which is a phase 3 clinical trial that involves patients from several different countries).

The first one is called "Obinutuzumab-Based Induction and Maintenance Prolongs Progression-Free Survival (PFS) in Patients with Previously Untreated Follicular Lymphoma: Primary Results of the Randomized Phase 3 GALLIUM Study." (This was selected for the "Plenary Scientific Session," which makes it one of the top six presentations in the whole conference. A big deal.) The study compared Rituxan + chemo + R-maintenance with Obinutuzumab + chemo + Obinutuzumab maintenance. So we have a direct comparison between the two anti-CD20 treatments. The way of comparing was Progression-Free Survival (PFS) -- which treatment allowed patients to go longest without having their FL get worse?

The study is still going on, with not enough patients having reached the median yet (that's a good thing), but the researchers assume that the Obinutuzumab group has a PFS about 1.5 times longer than the Rituxan group, which could be as much as 3 years of Progression Free Survival. That's pretty significant (and the ASH Selection Committee giving the session a place of honor would seem to be saying the same thing). It's been tough to find something that works better than Rituxan. This might be it (when it combined with chemo -- either Bendamustine, CHOP, or CVP) and followed with maintenance. The researchers suggest this should be a new standard of care.

The other study involving Obinutuzumab and the GALLIUM study is "Minimal Residual Disease in Patients with Follicular Lymphoma Treated with Obinutuzumab or Rituximab As First-Line Induction Immunochemotherapy and Maintenance in the Phase 3 GALLIUM Study." This one uses the same patients to argue that Minimal Residual Disease (MRD) is a way ti measure how effective a treatment has been. Basically, by figuring out whether or not the treatment has cleaned up all of the cancer cells, we can tell how likely it is that the cancer will return.

To find MRD, researchers looked at either blood samples of bone marrow samples to see if there were any genetic markers on cells that would show that they were FL cells. The samples were taken at the mid-point of the treatment and at the end of the treatment (remember, this is still the GALLIUM study, so patients had either Obinutuzumabor Rituxan + chemo + maintenance). The tests that looked for genetic markers are sensitive enough that the researchers could be sure that the disease was present. (Compare this to something like a PET scan as a way of measuring how well a treatment worked. A scan might not light up, but there might be a small number of cancer cells still hanging around -- too small to light up a scan, but not too small that they won't multiply and bring the disease back. It's a more effective way of measuring success.) So there were really two things being measured here. First, the study showed that MRD was a good way of measuring how successful a treatment could be. And second, because they measured for MRD at the mid-point and the end, that showed that Obinutuzumab was more successful than Rituxan at clearing out cancer cells quickly.

Together, the two studies show that Obinutuzumab is really good when it is combined with chemo and followed with maintenance. It might be a good replacement for Rituxan in that situation. The same combo was already approved earlier this year as a second-line treatment for patients who already had Rituxan as part of their first treatment. It will be interesting to see what other combinations show positive results from here.

Monday, November 7, 2016


ASH abstracts are here! Woo hoo!

Every year at the beginning of December, the American Society of Hematology holds its annual meeting, and some of the most interesting and exciting research in lymphoma is shared. It's an exciting time for a Cancer Nerd like me. This year, there are about 60 presentations that are related to Follicular Lymphoma, and as I've done in the past, I'll try to read and comment on the sessions that are most exciting and interesting to me.

An important thing to mention: there is lots of good stuff at ASH every year, but it's usually not peer-reviewed. That is, it hasn't been looked at and approved by other experts in the area. That doesn't mean it isn't valid -- it just means it might turn out to be not as exciting as it seems at first. Also, a lot of the research is very early, in phase I or maybe phase II trials, with small numbers of patients. Same warning there -- it might turn out later that the research wasn't as exciting as it had seemed.

But that doesn't mean we can't get excited about what might come in the future, right?

So let's start with this one: "T Cells Expressing a Novel Fully-Human Anti-CD19 Chimeric Antigen Receptor Induce Remissions of Advanced Lymphoma in a First-in-Humans Clinical Trial."

This one was on my list, and then I got an email from William, who comments here sometimes. The paper is reporting on a trial that William's wife is a patient in, so he has an interest in sharing the good results that are being presented.

The paper discusses one of the many variations on CAR-T therapies that are being tested these days. As the abstract explains, some CAR-T types are made with murine components (researchers are too polite to say "mice," so they say "murine"). Like Rituxan, which is also made with murine components, the body can have a reaction to those non-human parts of the treatment. So the researchers reporting here created a fully-humanized CAR-T treatment to get rid of that problem, one that seeks out the CD19 protein on lymphoma cells. The treatment is called HuCAR-19.

Patients were given low-dose chemotherapy (Cyclophosphamide, the "C" in CHOP, plus Fludarabine), and then the HuCAR-19. Some patients were given a second dose if things hadn't cleared up.

This was a very small study (11 patients), and researchers were interested in the safety of the treatment as much as the results. They got good news on both ends: there were some safety issues, but they were treatable. The safety issue they were most concerned about was
Cytokine-Release Syndrome. With CRS, so many cells are being killed at once that the body has an inflammatory response, and it can have very serious consequences, including death. The researchers were aware of this, and had treatment available. The other thing they were looking for, a Response to the treatment, was also very good -- an 86% Overall Response Rate. So HuCAR-19 has shown to be safe and effective in this small study, making it worth examining in a larger study.

The patients, by the way, had several different types of lymphoma. Two patients had Follicular Lymphoma, and both had Responses to the treatment. that's good news, and certainly something for us to all keep an eye on, should a larger study of just FL patients come about.

Back to William: his wife Gretchen was, as he said in his email, their "star performer." If you look at the link, she's Patient 2 in the chart at the end: a Complete Response and no CRS! Congratulations, William and Gretchen! I hope things continue to go smoothly.

(And if there's anything important that I left out, please let me know in the comments.)

And one more thing -- this is more great advertising for clinical trials. New treatments can't happen if people don't volunteer to test them out.

More on ASH in the days to come. Lots to be (cautiously) excited about.

Friday, November 4, 2016

Cubbies and Cancer (or, Lester and Lymphoma)

I've told this story a few times before, but I'm going to tell it again:

When I was diagnosed, my kids were 6, 8, and 10 years old. My wife and decided quickly that, even with the kids at that young age, we wanted to be completely honest with them about everything that was going on. We knew that they would figure out that there was a problem, and we thought that what they imagined would be worse than the truth. So honesty was our approach.

So when we told them, I sat on the couch my arm around each of my sons. My oldest was old enough at 10 to really understand what was happening, and he tensed up at the word "cancer." I told him it was a kind of non-hodgkin's lymphoma. "You've heard of that before," I told him. "It's the kind of cancer that Jon Lester had."

And I felt his body immediately relax, and he let out a big sigh.

Jon Lester was a pitcher for my beloved Boston Red Sox. In fall 2006, he was diagnosed with Anaplastic Large Cell Lymphoma, a much more aggressive form of NHL that Follicular Lymphoma (though my son didn't need to know that).  He came back the next season, and pitched well, winning the clinching game of the World Series.

I was diagnosed about 3 months later.

And about 4 months after that, he threw a no-hitter. I woke my son up so he could watch the last inning.

If you're not a baseball fan, and the details don't mean much to you, that's OK. You probably get the message -- Jon Lester was a hero to me, and to my son, and he got us through some tough times, just watching him. I wore a shirt with Lester's name and number on it for all of my Rituxan treatments.

So I was sad when he left the Red Sox two seasons ago to pitch for the Chicago Cubs, but that was OK. He gave me what I needed, and I wished him well.

And the well-wishes worked! A couple of days ago, the Chicago Cubs won the World Series, breaking a streak that was even longer than the Red Sox's streak. Lester played a big role all season for the Cubbies. He wasn't the only hero, but he played a big role.

But even cooler than that?

Another of the Cubs' heroes was Anthony Rizzo. In 2008, Rizzo was playing for a Red Sox minor league team when he was diagnosed with Hodgkin's Lymphoma. Lester helped him through the experience.

And now they both have World Series rings, make lots of money, and give a bunch of it away to help with cancer research and to support families of cancer patients.

I haven't done a "Nodes of Gold" episode in a long time, so you can consider this one of them.

Of course, a World Series winner means there is a World Series loser, and in this case, that was Cleveland. And the Cleveland manager is Terry Francona, who managed the Red Sox when they won the World Series in 2004 and 2007.

He's the same Terry Francona who sent my kids a letter in March 2008, telling them that the Red Sox were cheering for me.

So no Red Sox victory this year, but plenty to celebrate anyway. And it brought back some nice memories of happy times.


Something else to celebrate: abstracts for the ASH (American Society of Hematology) meeting are online. As usual, I plan to write about the ones that look promising or interesting to me.

Stay tuned.

Monday, October 31, 2016

Lessons from a Survivor

I came across this video from the Lymphoma Association (UK)'s Great Purple Collection, which raises funds for Lymphoma support.

(The Lymphoma Association also has a fundraiser called The Great British Tea Break. In the U.S., if we want to raise money for cancer, they usually make us walk, sometimes all night, sometimes for the length of a marathon, sometimes by running, biking, or swimming (or all three) instead of walking. I get it -- we're encouraging people to be healthy. But I really like the idea of raising money by drinking tea and eating cake. I am totally on board with that kind of fundraiser.)

The Great Purple Collection includes a series of videos of cancer patients discussing their experience, and this video of a man named Bernard really struck me.

Bernard was diagnosed with Follicular Lymphoma when he was only 20 years (which is very young for that diagnosis, as most of us know) in 1968, and because he was "under the age of consent," he wasn't really told anything about his disease. (And since it was 1968, there wasn't nearly as much to tell as there would be these days.) He was told he had Non-Hidgkin's Disease (it seems like they didn't even use the word "lymphoma").

A couple of lessons for me from Bernard's story:

First, we do know so much more now than we knew in 1968. We know more now than we knew in 2008, when I was diagnosed. It's amazing how far we have some. (And I keep saying "we" because, even though I'm in no way part of the research teams that are doing this, I'm one of their biggest fans, so I deserve as much credit as a baseball or football fan does for their team.) Even our attitudes seem to have changed in the almost 50 years since Bernard was diagnosed -- we're much more open about talking about cancer. That can only be a good thing.

Second, Bernard had had Follicular Lymphoma for almost 50 years! We've had some discussion in the comments in the last few weeks about Overall Survival statistics, and what they mean, and which to trust. As I've said before, I've learned to ignore the statistics that make me sad, and focus on the ones that make me happy. And Bernard's story makes me happy.

It makes me think of something that someone said in the support group a few years ago. Her doctor told her that with the advances happening in treatments for FL, if they could keep a patient alive for 5 years, they could keep him alive for 50. I think of that a lot.

Will we all be alive 50 years from now? Probably not. Can we apply Bernard's story to ourselves? No, we're all different.

But can Bernard give us some hope? Absolutely. There are 50 year survivors out there. A Follicular Lymphoma diagnosis is in no way a death sentence, and treatments will only get better from here.

I'm jealous of Bernard's Survival Statistic, and of his beautiful flowers, too. I'd love to put a bunch of them in a vase and serve you all a cup of tea.

And you better believe there will be cake.

Tuesday, October 25, 2016

Lymphoma Canada Survey on Obinituzumab/Gazyva

If you have been treated with Obinituzumab/Gazyva, Lymphoma Canada needs your help!

Lymphoma Canada is a support and advocacy group, based in Canada, that helps out Lymphoma patients. They are currently helping to gather information about Obinituzumab/Gazyva for the pan-Canadian Oncology Drug Review (pCODR), a government agency that makes recommendations for funding to the health ministries of the provinces.

Part of the information that the pCODR needs has to do with patient experiences with a treatment.

That's where Lymphoma Canada comes in -- they have developed a survey for Follicular Lymphoma patients whop have been treated with Obinituzumab/Gazyva.

You do NOT need to be Canadian, or live in Canada, to complete the survey.

I've written about how important it is to be part of clinical trials to help make new treatments available to patients. Think of this as another way of helping -- the information you provide might help make this treatment available to Follicular Lymphoma patients.

I'm not sharing this because two of my grandparents were from Nova Scotia, and Montreal is one of my favorite cities in the world. It's because it's really important that we help each other out any way we can.

The message from Lymphoma Canada is below. Thanks for your help.


Follicular Lymphoma Patient Survey

If you have follicular lymphoma and have been treated with obinituzumab (Gazyva) you can help by completing our survey.

Lymphoma Canada is preparing a submission for the pan­Canadian Oncology Drug Review (pCODR) for:
Obinituzumab in combination with chemotherapy, followed by obinutuzumab maintenance, for the treatment of patients with follicular lymphoma who relapsed after, or are refractory to, a rituximab containing regimen.

You can help by completing our survey, which will provide us with the patient input required for the submission. pCODR uses this information to help them make recommendations to the provinces and territories regarding funding for new cancer drugs.

You do not need to live in Canada to complete this survey.


The survey will be open until midnight Pacific Time on Friday, November 4th and should only take 10 minutes of your time.

You may access the survey at the following link:

Sunday, October 23, 2016

Expanding Treatment Options

Things have been very busy lately. I haven't had much time to read and write for the last few weeks. Work has been busy (and I'm always grateful to have a job I like, and the good health to be able to keep at it), and my kids' lives have been even busier. We saw my oldest son this weekend; he's been away at school, and we went down to see him, which was great. But now I'm way behind on everything, including Lympho Bob (but worth it to see my son).

So I have some reading for you to do, without much commentary from me. It's an article called "Treatment Options for B Cell Lymphomas Continue to Expand," from the most recent Cure magazine. Cure is often found in oncologists' offices (in the U.S., anyway), so chances are good that some of you have seen it.

The article discusses some of the newer treatments for B Cell Lymphomas, including Follicular Lymphoma) and makes the point that there are lots out there and lots more being developed. It's overall a very hopeful article.

I could object to a few of the details. I personally wouldn't call Follicular Lymphoma "an uncommon blood cancer," since it's the second most common type of NHL. I'm also not crazy about referring to treatment options as "alphabet soup," which seems to encourage people to just be confused about things and not do a little work to learn about the disease.

But those are small complaints, and mostly the article is very good at a few important things:
  • It is, as I said, very hopeful in painting a picture of the future of treatments for lymphoma. We have options, and more are on the way. We shouldn't ever lose sight of that.
  • It is pretty honest about the downsides of treatment. The patient that gets focused on in the article has Follicular Lymphoma, and the side effects she deals with are not pleasant. I know I often focus on positive things about lymphoma research, and ignore things like side effects. It's good to be reminded that treatments all have risks, and many of us know from experience.
  • The article makes a big point of the importance of clinical trials. Great treatments won't get to us without approval, and approval won't happen if patients don't participate in trials. For some patients, a trial might be the best option -- even better than treatments that were already approved. (You can find a clinical trial finder at Lymphomation, along with advice about whether or not a trial is right for you.)
So read the article. I'm going to take a nap and then get back to work.

More soon (I hope).

Monday, October 17, 2016

Follicular Lymphoma: Where We Are Now

Many thanks to the commentor who (just this morning) provided a link to a session on Follicular Lymphoma at the European Society for Medical Oncology meeting last week. (The commentor is listed as "Unknown," which is kind of cool -- we have lots of mysteries with FL, but The Unknown Commentor is kind of a fun mystery.)

ESMO 2016 took place in Copenhagen, and has tries to "bridges the gap between researchers, clinicians and patients and unites all stakeholders focused on finding the most effective cancer treatment solutions available today."

The link to the session is from LymphomaHub, and includes photos of slides from the presentation, as well as commentary. The presenter was Dr. Michele Ghielmini from the Oncology Institute of Southern Switzerland. The presentation is called “Follicular Lymphoma (FL): Novel Developments Beyond Chemotherapy.” Since it took place last week, it's probably about as up-to-date a discussion of Follicular Lymphoma as we'll find.

The link to LymphomaHub is pretty easy to read, and you can read the whole thing on your own, but I'm going to list a few things that I think are highlights.

  • Dr. Ghielmini is a big advocate of Rituxan. Chemotherapy does not provide much benefit as a first treatment for FL, especially when long-term side effects are taken into consideration. Chemo is best reserved for later treatments. That seems pretty well in line with what a lot of people are saying, though there are still plenty of oncologists who recommend R-CHOP or R-Bendamustine as a first treatment.
  • The current median Overall Survival rate for Follicular Lymphoma patients is about 15 years. He gets this from some recent published data. He also gives some other OS figures: FL patients younger than 40 have a median OS of about 24 years. There are lots of factors that determine whether a patient is on the plus or minus side of that 24 years, but it's a very encouraging number for those of us who were diagnosed at a young age.
  • Rituxan Maintenance is still controversial. There's lots of evidence that says it's a good thing, and lots that says it's not necessary. Tough decision for those who have to make it. Like many decisions with FL, I think it will come down to Quality of Life -- do you have the time and money to do it? Will doing it give you peace of mind?
  • R-Squared (Rituxan + Revlimid/Lenalidomide) seems to be as effective as Rituxan + Chemo, though there needs to be more long-term follow-up to see if the great response rates mean a long Progression-Free Survival (it helps lots of people at first, but will it keep helping them for a long time?).
  • "Small Molecules" or pathway treatments such as Idelalisib, Ibrutinib and Venetoclax. Dr. Ghielmini showed the most recent results for Idelalisib and Ibrutinib. We've known about these results for a while -- nothing new presented here. A little less well-known, though, are results from early trials for Venetoclax (also known as ABT-199). It's a BCL-2 inhibitor, and the latest data is from a very small phase 1 clinical trial for Follicular Lymphoma. (Maybe we'll see updated results soon?)
  • There are lots of trials that are investigating combinations of various treatments. There are lots of folks who think this is the best way to go. Single agents might work well, but cancer is sneaky enough to find ways around those successes. Blocking more than one path or attacking in more than one way seems like the best way to go.
  • Finally, the LymphoHub piece concludes with: "In future, we need to develop combinations based on the oncogenic alterations of each individual tumor." This is also probably true. As much as we can find general approaches that seem to work for lots of people, in the end, we'll probably need to find treatments that are based on biomarkers for each individual patient to give the best chance of success.
So, overall, this was a nice article for summing up much of what we know about Follicular Lymphoma and its treatment, as of last week, anyway.

But as Dr. C, the lymphoma specialist I saw a week after I was diagnosed, told me almost 9 years ago, "Anything you see online is already out of date." As up-to-date as Dr. Ghielmini's presentation is, it doesn't include everything (no mention of CAR-T, for example). And it doesn't include results from trials that we'll probably see in 6 weeks or so when ASH takes place.

And that's not a criticism of Dr. Ghielmini. It just means that we all have lots more to be excited about as Follicular Lymphoma patients. As great as things look right now, especially compared to 9 years ago when I was diagnosed, there's still lots more great stuff to come.

(Thanks again, Unknown Commentor, wherever you are......)

Tuesday, October 11, 2016

Follicular Lymphoma for Sale

So I was doing some research for a post, and I remembered that there was a web site that I had looked at a few days ago, but I didn't bookmark it, and I couldn't remember what the name of the site was. So I did a search for "Follicular Lymphoma," and I was scrolling through the results, and on page 2, I saw this:
"Lymphoma Follicular for Sale"? Well, this was something I obviously needed to explore. I mean, if someone is out there selling Lymphoma, then there must be buyers out there. And if someone is willing to buy, then I would be happy to sell them my Follicular Lymphoma. Really cheap. I'll even pay the sales tax. It's really good lymphoma, too -- I've hardly used it for the last 6 years or so.

(The search engine I was using, by the way, was not Google. Because Google wouldn't so something like advertise Follicular Lymphoma, or Lymphoma Follicular, as being for sale. That would be weird, and they wouldn't so that, and Blogger, which hosts this blog, is owned by Google, and wouldn't do anything to upset my blogging Overlords.)

So anyway, I get this weird result in my search results list, and I really have no choice but to click on it, because how could I resist?

My click brought me a shopping site, and the first result was this book:

But here's the kind of strange thing: it was being sold by WalMart. I know you can get pretty much anything at WalMart, but this is a study guide for medical students who are preparing for their board exams. I've never read this book, so this isn't an endorsement (though WalMart did encourage me to be the first to review it). But it's good to know that WalMart is there if I have any medical-boards-level questions about cancer.

The rest of the page, and the next two page, were lists of more books about Follicular Lymphoma, other kinds of lymphoma, and cancer in general. Some looked like the same kinds of study guides as the first one. Others looked like self-published stories from cancer patients and caregivers (all my love to you folks -- I hope someone reads your stories and they are helped by you).

But then it got really weird, because the next page was stuff like shoes, a waffle iron, a vaccuum cleaner -- things that didn't seem to have any connection to Follicular Lymphoma (or Lymphoma Follicular). I clicked on some of them to see if there was something in the ads that was related to FL, and there was nothing that I could see. I was expecting SOME connection -- proceeds from the sale of the waffle iron go to, or something like that? But, no. It was just a waffle iron.

But this did get me thinking about how little I see about Lymphoma in the world when I'm not looking for it. I'm probably especially sensitive to this during this particular month, when my bread has a pink wrapper and local businesses are pushing their "Cookies for Boobies" promotions and the like.

Lymphoma Awareness Month was in September, and I worry that maybe we're not doing as good a job as we could be in making people aware. There's lots of good stuff happening in the Lymphoma World -- new treatments, new approaches, new ideas. And "awareness" is important on its own, but more important is doing things like pushing for more funding for Lymphoma research, or considering a clinical trial for treatment, or writing to someone who can help save RadioImmuno Therapy.

Some folks celebrated a new year a few days ago, but maybe we can all make a new year's resolution today to be advocates, not just for ourselves, but for all lymphoma patients. We're in this together.


Wednesday, October 5, 2016

More CAR-T Awesomeness

Lots of people are getting excited about the things that CAR-T treatments can do. Just when you thought it couldn't get more awesome, a new study in Cell gives us reason more reason to be excited about CAR-T for Follicular Lymphoma.

(But before I go on, I want to thank a reader named Ben for sharing his experiences with CAR-T in the comments section of a post from a few weeks ago. I didn't get a chance to respond to the comment, which is a great mix of hope for the future of this treatment, and caution about some of the side effects. Please do read Ben's comment when you get a chance.)

The article is called "Loss of the HVEM Tumor Suppressor in Lymphoma and Restoration by Modified CAR-T Cells." Here's what it says:

So far, CAR-T cells are used as ways to help the body's immune system recognize and attack cancer cells that would otherwise get past those defenses. T cells, which usually attack invaders, are removed from the body and changed so they recognize the cancer cells as invaders. It's been a pretty effective treatment so far (again, I suggest you read Ben's comment).

But CAR-T cells can do other things, too. Because they focus in on cancer cells, they can also be used to deliver things to those cells. It's kind of like RIT, which identifies cancer cells and delivers a tiny dose of radiation. CAR-T can deliver things that don't just kill the cell, but repair it instead.

The researchers know that many cases of Follicular Lymphoma cases involve a gene called HVEM. Whn HVEM is mutated (as, of course, it is with Follicular Lymphoma), it cannot interact with a protein called BTLA. When that happens, bad things happen -- cancer cells go crazy.

(This is another of those pathway things that we're learning more about. When everything is working OK, calls behave themselves. Mess with the pathway, and all hell breaks loose. It's like a fence that keeps pigs on a path between two pens. If the fence breaks, that path gets messed up, and the next thing you know, there are pigs all over town.)

So here's where CAR-T comes in. The researchers figured out that the HVEM gene can be repaired if the HVEM protein can be delivered to the cell.  The CAR-T cells can be told to find cells that have the CD19 protein on the surface, which is a protein Follicular Lymphoma cells have. When the CAR-T cells find it, they can deliver the HVEM protein to that cell, and the cell can be repaired. No more HVEM mutation, no more messed up pathway, no more cancer. The pigs stay in the pen.

But here's what makes CAR-T so amazing.

In addition to changing T cells in CAR-T cells, researchers were also able to program the cells to keep producing the HVEM protein. T cells are meant to find an invader and then multiply and find any other similar invaders. CAR-T cells are no different, and neither are these special CAR-T cells. They will keep producing that HVEM protein, finding other cancer cells, and getting the protein to them, too. One article calls them "mini-pharmacies" -- they keep traveling around and producing the treatment that the cancer cells need. Very cool. Because the CAR-T cells are delivering a protein that only mutated cells will need, the thinking is that healthy cells will be spared, and there will be fewer side effects.

As exciting as this is, right now, it has only been tried on animal models. No humans yet. But the researchers think that their work justifies carrying on with this approach to see how well it really works.

There's definitely reason for hope with CAR-T. As relatively new as it is, we're already seeing variations of it, like this one, that seem to improve on it.

Lots to look forward to.

Sunday, October 2, 2016

Radiation + Chemo for Stage 1 or 2 FL

I've seen a bunch of news stories about this (like this one), so I thought it was worth discussing: last week, a presentation at the American Society for Radiation Oncology showed that adding chemo to radiation treatments can greatly improve Progression Free Survival for Follicular Lymphoma patients with stage 1 or stage 2 disease.

(I looked for the abstract in the ASTRO program online, but I just couldn't find it, so I'm going by the news stories that I've been reading.)

The study focuses on stage 1 and 2 Follicular Lymphoma. I'm sure most of you know which stage you were diagnosed at, and it was probably 3 or 4. Because FL patients usually don't have any symptoms, it doesn't show up until it has reached stage 3 or 4. Stage 1 or 2 means the disease is concentrated in one or two areas of the body, above the diaphragm. (See's explanation here.)

Because the disease is focused on only one or two areas, it can often be treated with radiation, the way some solid cancers can be treated. In this study, the researchers used Involved-Field Radiation Therapy (IFRT), which means radiation is used only on the immediate area where the cancer is found. (Extended-Field Radiation Therapy is also used on some cancers, but it covers a larger area of the body and can lead to more side effects, short- and long-term). Radiation is often used on stage 1 and 2 FL, because the cancer is in a small space. Some patients are even cured with radiation alone (one article I read says it might be 50% of them).

But that's not true for everyone who is stage 1 or 2. And for those folks, the study says that following up with chemo (specifically, CVP or R-CVP) will increase Progression-Free Survival, the time it takes until the cancer comes back or gets worse again. Of the patients in the study, the 10 year PFS for those in the radiation + chemo group was 59%. The radiation only, with no chemo, was 41%. Pretty good.

I think this is great for patients who are stage 1 or 2, and deserving of the attention it has been getting, but I have some thoughts:

  • First, this effects a pretty small number of FL patients. One of the articles says only about 2% of FL patients are diagnosed at stage 1 or 2; I've seen it as high as 15%. but either way, it's a small number of us. This is great news for those patients, but it isn't going to mean much for the great majority of us, since IFRT isn't appropriate for us.
  • Second, while the PFS saw a lot of improvement, there was no difference between the two groups in Overall Survival. It may take longer until the next treatment, but it won't affect how long the patient lives. So that's a mixed blessing. There are a lot of treatments in the same situation -- it's really hard to increase Overall Survival for FL patients.
  • Third, this was a really long-term study, so it used CVP (which is CHOP, but without the component that damages your heart). I see fewer and fewer new studies involving CVP, so I'm not sure how useful it's going to be compared to newer treatments that don't involve traditional chemo, but instead use those cool new targeted pathway treatments.

So, in some important ways, the study is limited. However, there are definitely some good things about the study, too:

  • This is a little bit of a stretch, but this might reinforce the idea that radiation is a useful treatment for FL patients, and maybe RadioImmunoTherapy is something we need to keep pushing for. IFRT and RIT are different in the details, but they share a similar approach -- zapping those darn cancer cells until they glow like Fenway Park during a night game. If you haven't done your part to help save RIT, then get to it.
  • The real value to this, I think, is that it was such a long-term study. They followed these patients for a median of 10 years (half of them longer than that). That's important. Our disease is a long-term disease, and it helps us to see how things work out long-term. there's a push now to approve treatments after a short term, maybe as short as 1 or 2 years. But studies that follow patients for a long time help us see how the treatments affected not only our PFS and OS, but our lifetsyles as well. So if this is an example of a long-term study that shows some good, maybe we'll see more of them.
For any of you that have stage 1 or 2 Follicular Lymphoma, I hope you see some good stuff here.

Tuesday, September 27, 2016

Advice on Watching and Waiting

Over the summer, Cancer Today did a piece on Watching and Waiting in blood cancers called "Treatment is Waiting."I missed this somehow.

Cancer Today is published by the American Association for Cancer Research, which is made up of cancer researchers. They publish a number of medical journals, but Cancer Today is aimed at patients, their caregivers, and their families.

The article is decent. It describes what watching and waiting is, and how and why it is used. The examples are patients with Chronic Lymphocytic Leukemia, or CLL, which is another indolent, slow-growing blood cancer, like Follicular Lymphoma.

The stories are familiar to a lot of us -- someone who is perfectly healthy gets a blood test that comes back a little funny, or notices a lump that won't go away. A few tests, and there's a diagnosis of an indolent blood cancer.Some discussions with the oncologist, and they agree that watching and waiting is the best choice. (The article provides a link with the blood cancers that are likely to involve a watch and wait option.) The article lays out some reasons why this treatment choice makes sense (and a bunch of us have heard them, too) -- the cancer is growing slowly enough that treatment is necessary right away, and holding off treatment means holding off its side effects, too. The article finished with some studies that involve watching and waiting, to see how that decision holds up against some newer treatments.

Like I said, I think the article is decent. And it's easy to wish a writer had a different purpose and made different decisions. But I wish an article in a magazine aimed at patients would have spent more time discussing the emotional aspects of watching and waiting. The focus is on clinical trials because it's from a group devoted to research. And trials certainly are important. But for patients making the decision to hold off on treatment, they need to know and understand that there is an emotional investment in this option. The purpose of the article was not to highlight that, so maybe it's a good time to look at it again.

The article does acknowledge that emotional aspect. One patient whose story is told did remark on how strange it was to hold off on treatment. And there's a link with "Tips for Blood Cancer Patients" that includes "Get help managing the anxiety that can sometimes accompany 
watchful waiting."

Sometimes accompany it? I haven't heard of anyone who didn't have some anxiety. There's a boatload of anxiety that comes with that decision. It makes no sense, to a new patient, to get a cancer diagnosis and then purposely "do nothing about it." It takes a long time to not worry about every bump, every red mark, every cough, when you are supposed to be "watching." It means a lot of lying awake in bed, wondering of you made the right decision, and dreading that you didn't, and panicking over the penalty that you'll pay as a result.

So, yeah, I'd say that some anxiety can sometimes accompany that decision. And I'd say that it's a good idea to "get help managing" it.

For me, as I've said before, that help came from an online support group. The people there had lots of different types of NHL, and even if their experience was different from others', they always had an encouraging word, and they were always there to celebrate the good things. And with hundreds of people there from all over the world, even with all those different types of NHL, there was always someone who did know how you were feeling, and did know what you were going through.

And I talk about the support group in the past tense, because even though I still check in every day, I don't post as much as I used to. Because that's another important thing to know about watching and waiting: at some point, you do stop worrying constantly. You don't stop worrying completely, but you sleep better, and you panic less, and decide that it was the right decision. Someone in the support once said that it takes about 6 months for that to happen. That sounds about right. Maybe a little longer, or shorter. But the worry doesn't last forever.

And if it does? If you just can't stand the idea of watching? Then get some treatment. There's no shame in it. If the oncologist recommends holding off on treatment, there's no rule that says you have to take that advice. There is no consensus in the oncology community that watching and waiting is the best choice. It's easy to find experts that say it's better to just treat right away. If you can't stand the idea of "doing nothing," then do something. Sleep better.

Watching and waiting is, in the end, all about maintaining a good quality of life. If that means holding off on treatment and its side effects, that's great. If it means having treatment and getting rid of your anxiety, then that's great too. It's about having some say in your own treatment and feeling good about that decision.

I'd be interested in hearing about your own decisions with watching and waiting, and how you coped with the emotional side of it all. And I'm sure some newer readers would like to hear it, too.