More on Follicular Lymphoma Treatments

Following up on the OncLive Peer Exchange that I wrote about a couple of posts ago.

As I said then, Peer Exchange is a video series with a panel of experts on a particular cancer-related topic.The current series is called "Evolving Paradigms for B-Cell Non Hodgkin Lymphoma," and it focuses on treatments for Follicular Lymphoma. The series releases a new video every few days. They have released a few since that first one I described.

Here's a quick summary of the stuff I found interesting in those videos:

Follicular Lymphoma: Consolidation and Maintenance
The panelists have some doubts about Maintenance Therapy, and discuss two studies that have mixed results. The first is the RESORT study, which showed that patients who have treatment and then wait until they need another treatment, do just as well as those who have treatment and then immediate Maintenance. The other study, the PRIMA study, found that a percentage of patients (15%) get a longer Progression-Free Survival with Maintenance than those do don't get it, but no Overall Survival benefit. This comes as the results of the GALLIUM study were being presented at ASH -- this study showed that Obinutuzumab + chemo + maintanence did have an imporved PFS over Rituxan + chemo + maintenance. It was also controversial, though, in showing higher toxicity compared to Rituxan. This only seemed to add to the mixed reaction that the panelists had.

obinutuzumab

Sequencing Therapies for Follicular Lymphoma
I have always found the idea of sequencing pretty fascinating. It's tough enough to know which treatment to try first for FL, and harder still to know what to try second and third. Panelists discussed things like FLIPI scores to help figure out which patients are high-risk, and more importantly, m7-FLIPI, which uses genetic markers to make that identification even more accurate. Dr. Leo Gordon discusses the GADOLIN study, which compared Obinutuzumab + Bendamustine with Bendamustine on its own. The results showed some good results for O + B, but Dr, Gordon also had some problems with the way the study was set up that might make the results better than they seem. He also talks cautiously about Idelalisib, especially after other treatments like Bendamustine (it is approved for patients who have already had another treatment). Because Idelalisib leads to suppressing the immune system, it's important that treatments before that have also not affected the immune system too much, which can lead to very serious side effects. At the end of the video, he mentions RadioImmunoTherapy; he says he has patients who had one treatment 15, 16, or 17 years ago and are still in remission......

R2-CHOP for Relapsed Follicular Lymphoma
I was hoping the panel would continue the discussion of RIT, but alas, they didn't. Instead, they jumped to R-Squared, Lenalidomide (or Revlimid) + Rituxan. The R-squared study being discussed was with Relapsed patients (who had the disease go away and then come back), not Refractory patients (who had a treatment fail to get rid of all of the disease). R-squared worked very well on relapsed patients, with about 75% responding and a PFS of about 2 years. Nice. Another phase III trial is looking at the R-squared combo as well. And despite all of the "new toys" we have (as Dr. John Leonard puts it), for some patients, a treatment like a Stem Cell Transplant might be the best thing.

I get the feeling that this series isn't finished yet, so there may be a few more videos coming with discussion of even more treatments.

I'm finding it very interesting because of the critical nature of their comments. These are genuine Lymphoma Rock Stars, and it's fascinating to hear them talk about some of the concerns they have with the results of trials. That isn't something that I see very often; it's not like there's a "comments" section on a medical journal article, like there is on an internet article, where readers can bring up questions. So I've been enjoying hearing these folks talk about various treatments that all sound great when I read about them in other places.

I'll post more if I see more videos from the series.

Indolent Lymphoma Survey

I have another request for you.

Patients Against Lymphoma (PAL), the organization that runs the Lymphomation.org website, has put out another call for patients with indolent lymphomas to complete a survey. Of course, this includes those of us with Follicular Lymphoma.

The survey asks you to describe the treatments you have received and discussed with an oncologist. It also asks you to describe the type of setting you received treatment in -- a research hospital, a small clinical practice, a private practice, whatever.

The idea behind the survey is to gather more data to help make a case that RaioImmunoTherapy (RIT) is not only worth having, but that new regulations (about which doctors can give it to patients) are making it hard for this treatment to get to patients. So it's important to be clear about not only the treatments you received, but also the treatments that your discussed, especially RIT, and the place you received treatment (and thus the type of training that the doctor probably had).

RIT works. And it's on its way out. One form of RIT, Bexxar, is no longer being used. Another, Zevalin, is in trouble.

The survey will take about 5 or 10 minutes to complete. It's a really simple way for you to do something for yourself and other lymphoma patients.

Thanks for your help.

Follicular Lymphoma: When to Treat?

OncLive has a great series called "Peer Exchange."  It's a series of videos on different cancer-related topics with a group of experts in the area. Their most recent one is called "Evolving Paradigms for B Cell Non-Hodgkin Lymphoma," and it starts off with a discussion of Follicular Lymphoma. The first video in the series is called "Follicular Lymphoma: Triggers to Initiate Therapy."

The series has some great oncologists, and the one who does most of the talking in this first video is Dr. Leo Gordon from Northwestern University and the Lurie Cancer Center in Chicago. He is asked to talk about what triggers therapy -- when do patients need to start treatment?

Interestingly, he starts by saying he still takes a watch-and-wait approach with most of his patients. (As many of you probably know, there's an ongoing debate about whether or not to watch and wait, or whether to just start with treatment like Rituxan right away. As a watch-and-waiter, I'm always interested in what experts have to say about this.

Dr. Gordon favors watching and waiting because, he says, there is no evidence that treating earlier leads to better survival rates. He makes the decision to begin treatment based first on B symptoms (things like night sweats or fevers) that suggest a more aggressive version of FL, or size of lymph nodes. However, he will consider smaller lymph nodes if they are pushing on something important. (This is what happened to me -- a fairly small but well-placed node near my hip was blocking things and making my leg swell up.)

Once the decision is made to treat, there are options, including Rituxan, R + chemo, and other, newer options (he mentions Lenalidomide, or R squared). As for chemo, CHOP has been historically the most popular, but Bendamustine seems to have become the new standard. Interestingly, he mentions that his main concern with Bendamustine is the lack of long-term follow-up, and he worries about long-term side effects, something that came out at ASH this year.

Dr. Gordon also suggests that targeted treatments may replace chemotherapy. He mentions a Swiss study (which doesn't sound familiar to me) that suggests that Rituxan and Rituxan Maintenance are bringing improved disease-free intervals in FL patients.

The "Peer Exchange" series doesn't publish all the videos at once, but instead puts out a new one every few days. As I'm writing this, they have posted the second and third videos in the series -- "Follicular Lymphoma: Consolidation and Maintenance" and "Sequencing Therapies for Follicular Lymphoma." You can find thumbnails for them underneath the main video. There is also a transcription for each video.

I'll look at the next videos in the series soon. I'm always interested in sequencing therapies -- figuring out which treatment to try first, but then which to try second and third, if necessary. (I always like to plan ahead.)

So more on this soon, though I also encourage you to watch them on your, too.

prolonged disease-free intervals in patients getting Rituxan alone - See more at: http://www.onclive.com/peer-exchange/nhl-treatment-paradigms/follicular-lymphoma-triggers-to-initiate-therapy#sthash.Z6G3r2WD.dpuf

9 Years

Today is my diagnosiversary. I was diagnosed with Follicular Lymphoma 9 years ago today.

That means it's also the 7th anniversary of my first Rituxan treatment.

And, as always, I get a little reflective on my diagnosiversary. I think about where I have been and where I might be going. Bear with me.

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I've been wrestling with a Big Question for 9 years now:  If getting cancer changes us, then who is it that we become?

Does cancer define who I am now? Am I Bob the Cancer Patient? Bob the Survivor? Bob the "Hero"?

Or is cancer just the thing that changes us, like a car that we drive to a new place. And now once we are here we can just leave it behind?

I guess that's possible (leaving it behind) for lots of cancer patients. But maybe not so much for someone with an indolent, incurable cancer. I didn't get a Complete Response 7 years ago. The Rituxan knocked it back, but there was still some showing up on the scan. And I haven't had a Complete Response for any of the scans I have gotten since then. As far as I know, I have always had at least a little cancer in me, for 9 years (at least).

I have thought about my cancer every day for 9 years, without exception. Not just cancer. My cancer.

Cancer has been a part of me, physically and mentally, for 9 years.

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I write a lot. (Am I Bob the Blogger? Bob the Writer? Bob the Cancer Nerd?)

Not just the blog -- I write lots of other stuff, too. A couple of weeks ago, I came across an article that talked about creative writing -- fiction and poetry, stories and poems -- and how non-fiction (basically, stuff that isn't made up, like this blog) is not really valued by people who do "creative writing." Whether or not I agree with that article isn't important (and if you're really curious, the article is here, though you don't need to read it to get what I'm saying). 

The article got me thinking.  I don't write fiction or poetry. I'm not good at it. I write lots of non-fiction, though, like all of the stuff I write for the blog.

It was that term "non-fiction" that got me thinking. It got me thinking about Non-Hodgkin's Lymphoma. My blog is non-fiction about Non-Hodgkin's.

Ha. That's kind of cute, right?  But also kind of weird -- two things that I spend a lot of time thinking about, and they are defined by what they ARE NOT, instead of what they ARE.

Which brings me back to the Big Question: If getting cancer changes us, then who do we become? Are we defined by something we are?  Cancer patient?  Survivor?  Hero?

Or are we defined by something we are NOT? Healthy? Whole? Free from worry?

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It is true that I think about cancer every day.

But it's also true that I think about being a father. And a husband. And, most days, I think about being a writer, and a Red Sox fan, and a gardener. And lots of other things.

So if today is a day of reflection, and I'm looking back at 9 years, I'd say the lesson that comes to me is this: Cancer can't define us. We define who we are.

I don't think I could have said that 9 years ago. Or even 8, or 7. It takes some time and distance. And I've been blessed with both.

I can embrace the fact that I am a cancer patient, without letting it define who I am. I can't stop thinking about it, any more than I can stop thinking about being a husband and a father. But I tuck it away and take it out when I need it.

It's easy to let cancer be who we are, especially when we're first diagnosed. And it can be overwhelming. It can be define who we are (cancer patient) and who we are NOT (healthy and whole). That's when it gets bad. That's when you have to really think hard about something other than cancer. That's when you have to decide who you are going to be.

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I remember, long ago, soon after I had been diagnosed, having an odd conversation with someone about cancer. She had recently been to a cancer walk, or sponsored someone who walked. I forget. But she told me that she and a friend with cancer had been discussing her friend's status. She told me that her friend, who had recently celebrated 5 years in remission, had told her "When you have been cancer-free for 5 years, then you are a Cancer Survivor. Before that, you are a Cancer Victim."

I bugged me then, and it bugs me now, just thinking back about it. I might consider myself a lot of things -- Cancer Patient, Cancer Nerd, whatever -- but I sure as hell have never considered myself a victim. Self-victimization is an invitation to helplessness. And I'll never consider myself helpless.

That's the point of the blog, isn't it? Seek knowledge, and you can't possibly be a victim.

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So, has cancer changed me? Of course.

Do I know who it has changed me into? Not really. I'm still becoming him. But a lot of who I am and become is going to be my choice.

I want to thank you all for finding the blog, and coming back again and again. As a writer, I can say it's been pretty fantastic to know that people are reading your words, and even better hearing that those words help some of you. That's made the last 9 years so much easier for me, and has certainly helped me figure out my role in all of this.

I wish you all the same 9 years of good health, plus many more.

ASH: A Quick Bit of Hope

The Video Journal of Hematological Oncology has posted a short (2 minutes) video of Dr. Nathan Fowler from MD Anderson Cancer Center, commenting on indolent lymphomas (like Follicular Lymphoma), and I thought it was worth linking to. You can find the video here. It's one of those videos that doesn't really say anything new, but it says those things in a really, really hopeful way.

Dr. Fowler did a presentation at ASH on the history of chemotherapy in lymphoma, so he looked at about 40 years or so of treatments, and how they have changed.

"Most patients," he says, "will never die of Follicular Lymphoma." Median survival of low-grade Follicular Lymphoma is "around 18 to 20 years," according to Dr. Fowler. If the average age of diagnosis is 61 years old, then that puts the average patient pretty close to general population in terms of survival. (Of course, those are statistics, and individual patients will all have different experiences.) Patients can treat the disease more like a chronic illness, being managed over their lifetimes.

He also points out that this means oncologists will need to pay more attention to long-term toxicity, how many courses of treatment the patient gets, and the financial burden that treatment will place on them. If you treat it as a manageable chronic illness, then it can't cost too much, and it can't do more damage than it fixes.Quality of life is going to matter if it's going to be a long life.

Dr. Fowler also mentions some newer treatments like R-squared and Ibrutinib, and check point inhibitors, and "they might ultimately lead to a cure, or at least prolonged remissions."

He ends with, "So it's exciting."

I always love to hear smart people talk about the things they excite them (especially when those exciting things affect my health).

It's a short video, but a good one. Watch it now, and save it for a day when you could use a little injection of hope.

What We've Learned About Maintenance

Following up on my last post, which looked at potential problems with toxicity in Bendamustine when combined with maintenance (either with Rituxan or Obinutuzumab, both of which are anti-CD20 monoclonal antibodies):

It's interesting that the GALLIUM study, which seemed to show that Obinutuzumab was superior to Rituxan in certain situations, also gave us some information about maintenance. The maintenance information was not the main focus of the study, but it came out afterwards when people who were at the session looked more closely at the data. (I don't want that to sound like the presenters were trying to hide anything, because they weren't; it just wasn't the main focus of the session.)

Interesting, too, that another session (which I wrote about here) had something similar happen. The focus of the study was on patients who had not yet been treated receiving R-CHOP, the RadioImmunoTherapy, and then 4 years of Rituxan Maintenance. Like the GALLIUM trial, this one had great results: a 99% Overall Response Rate, with 95% Overall Survival after 5 years.

But in a video describing the study, the lead researcher, Dr. Paul Barr, points out (very quickly at the end of the video) that "prolonged maintenance therapy" might not be good for the "elderly population" in the study. (The median age for the study was 52, with a range from 29 to 80 years old. I'm a few months away from 50, so I'm trying not to take that "elderly" comment too personally.....Really, the video was cut off right after that comment, so he might have gone on to explain that the long-term maintenance was a problem for the older patients in the study, not all of them. Again, I'm not saying he's trying to sneak something in there.)

When I say they're both "interesting," I mean that I find it fascinating that we got information about maintenance when that wasn't necessarily the main point of the study. Science works that way a lot -- you're looking for one thing, and you end up discovering something else. But I find it fascinating.

So what did we learn? Well, for me, we learned that maintenance isn't as easy to think about as we have been trying to think about it.

Whether or not maintenance is a good idea is one of those controversies in Follicular Lymphoma that seems really hard to answer. There have been lots of studies that have seem to say "Yes, it's a good idea," and then others that say the opposite -- and neither that comes up with the answer very strongly (it's always "Yes, kind of" or No, not really, but....").

And I don't think either of these studies gives an answer, either. If anything, it complicates the whole situation.

And you what? That's a good thing. And maybe exactly what we should have expected.

We've never had any easy answers when it comes to Follicular Lymphoma. So why should we expect this question to have one?

It seems like we're finding out that maintenance works sometimes, for some people, in some situations, for some circumstances. The same as pretty much any other treatment. But we're also finding out which times, people, situations, and circumstances it helps. And that's what's important. At some point, we're going to be able to figure out who a treatment is going to help before they start getting the treatment.

This is probably a good time to remind everyone that it's important to consider clinical trials when it comes time for treatment. The only way we can figure out who will be helped by treatments is to study them closely and carefully under rigorous conditions. And that means people need to sign up for trials. As always, Lymphomation.org has lots of information about clinical trials and how to find them.

ASH: Bendamustine and Toxicity

We're going back to the ASH conference, looking a little deeper into one of the presentations that delivered some good news. The session discussed results of the GALLIUM study, which showed that in some situations, Obinutuzumab (an anti-CD20 monoclonal antibody) worked better that Rituxan.

However, the data from the study also delivered some bad news -- about Bendamustine. It wasn't the focus of the ASH session, but it got some people talking, and made them very surprised.

I've been hesitating to write about this for a couple of weeks until I worked through it, but now I have and I'm ready to write. But because Bendamustine is a popular treatment for Follicular Lymphoma, I'm asking you to PLEASE read all the way through. I think the best discussion of the bad news about Bendamustine comes from the article "Bendamustine Toxicity in FL Raises Eyebrows -- and Questions" from Medscape Medical News. Read all of that article as well. (You might need a password to get in, but the account is free.)

So here's the deal:

In the GALLIUM study reported at ASH, 1202 patients were given either Rituxan + chemo, followed by Rituxan maintenance, or Obinutuzumab + chemo, followed by Obinutuzumab maintenance. Overall, the study found that patients in the Obinutuzumab arm had a higher Progression-Free Survival -- significantly higher. One of the big problems with Obinutuzumab was that it had higher toxicity that Rituxan, so patients had more side effects and more problems overall, in addition to having a longer PFS.

But then they broke things down a different way, looking at the different chemotherapies that were combined with Obinutuzumab and Rituxan. They found that of the three, patients who took Bendamustine with either O or R had a higher instance of death that with the other chemotherapies (CHOP or CVP).

This is what "raised eyebrows" at ASH -- a treatment that has been very popular in the last few years has an increased death rate over other options. Researchers reported 19 deaths for patients taking Obinutuzumab + Bendamustine (about 5.6% of that group in the study), and 15 deaths for patients taking R + Bendamustine (4.4%). For those taking CHOP or CVP, only 9 deaths occurred.

 Definitely not what we want to hear. HOWEVER, this is why that Medscape Medical News article is so good -- they interview some very smart people who have lots of experience with Bendamustine, to get an explanation and to find out how this new data will affect the way they treat patients.

In a nutshell, it doesn't change things in a really drastic way. The experts interviewed will either continue using Bendamustine the way they have been using it, and/or will be more careful about how they use it.

For example, one of the experts interviewed is Dr. Bruce Cheson (lots of you know how much I respect Dr. Cheson and his work). Here's what he has to say about the study:

"I was quite surprised by the toxicity [reported for the bendamustine arms in the GALLIUM study]. It has not been my experience," Bruce D. Cheson, MD, professor of medicine, head of hematology and deputy chief of hematology-oncology at the Georgetown Lombardi Comprehensive Cancer Center, Georgetown University Hospital, Washington, DC, told Medscape Medical News.

Dr Cheson uses bendamustine for most patients with previously untreated FL. Although the data from the GALLIUM study are compelling and support use of obinutuzumab because of the advantage in PFS, its efficacy is counterbalanced by a higher level of toxicity, he noted.

"There may be a select patient population, such as the younger, fit patient, in whom I may use G-bendamustine in preference to R-bendamustine," Dr Cheson said. "However, for most, R-bendamustine remains my standard," he said.

For patients in whom there is a suspicion of occult transformation, Dr Cheson uses R-CHOP as induction in preference to R-bendamustine.

Some things worth noting here: In his experience, Dr. Cheson has not seen this kind of problem with Bendamustine. I think that's important. A clinical trial like the GALLIUM trial provides important, controlled data to help us understand how a treatment works in a large group. But it also controls the circumstances under which it is used. In this case, the GALLIUM study uses Bendamustine with a monoclonal antibody, and THEN follows that up with 6 months of maintenance.

At least one expert thinks that it is the maintenance that might create the problem. Bendamustine suppresses the immune system, and when you follow that up with an antibody that kills immune cells, it makes sense that there is a greater chance for infections. (Although not all of the deaths occurred because of infections.)

So some of the experts interviewed won't change the way they do things, and will keep giving patients R-Bendamustine, but perhaps without maintenance. Others will focus more closely on the individual patient, and what his or her body might be able to handle. Some may use CHOP or CVP if they plan to use maintenance, while others may use O + Bendamustine for the initial treatment,but then Rituxan for maintenance.

For me, I'm getting two big lessons from this.

First, Bendamustine is still on the table. My old oncologist, Dr. R, had always said that Bendamustine was going to be a consideration if and when I needed treatment again. This hasn't scared me off. I trust the experts that were interviewed, and none of them announced that they were giving up on Bendamustine, only that they were going to ask more questions about it.

Second, I think this will slow things down. As one of the experts noted, Bendamustine was pretty quickly adopted as a preference over CHOP, based on one particular study. Other studies backed up its effectiveness and safety. But maybe there needs to be more nuanced examination of who will benefit from the treatment. Maybe this will slow things down a little, and force patients (like me) from being so enthusiastic about it. That doesn't mean I wouldn't take it -- it just means I need to have a longer conversation with my oncologist about whether it's right for me, given whatever circumstances lead me to need treatment.

I'm sorry I couldn't start the New Year of with something more positive. It seems like everyone I know is looking for something to be positive about in 2017. But if nothing else, this is a good reminder -- and a good time for it -- that we should be active patients who take as much control of our own treatment as we can, asking questions and demanding answers, and not accepting what we hear about or read about online (including this blog).

Stay healthy everyone, and have a great New Year.