Age, Race, Sex, and Follicular Lymphoma

An article that will be published in the next issue of The American Journal of Hematology looks at "The Impact of Race, Age, and Sex in Follicular Lymphoma: A Comprehensive SEER Analysis Across Consecutive Treatment Eras." Basically, the authors looked back at the records of about 18,000 patients with Follicular Lymphoma from 1992 to 2009 to see how they did. (A SEER analysis is a look at the Surveillance, Epidemiology, and End Results database from the National Cancer Institute. That's important to know -- the researchers looked at electronic records, not actual patients.)

One of the things they really wanted to look at was the differences between two eras of treatment: 1992 to 2000, and 2001 to 2009. The separation, of course, is due to Rituxan; era 2 in this study is often called "The Rituxan Era," though it sometimes is given an earlier starting date. The 2001 date here is probably a reference to when Rituxan was used widely.

So, this is a study of statistics from the past. It doesn't say much of anything about any of us in the present. That's important to know, too.

Researchers found that, basically, things got a whole lot better once Rituxan came to town. We already knew that, of course, but this is the first time we get a sense of who seems to have benefited, in a general way, and how.

I'm not going to break down how particular ages, races, sexes, and classes did. I think there's some value for researchers in knowing those things. Maybe knowing that (and I'm making this up) working-class white men in their forties with blue eyes did worse in the Rituxan era than they did before (and, again I just made up that statistic) would lead some researchers to start asking why Rituxan wasn't working for them, and figure out if age or race or something else plays a role in Rituxan's effectiveness. I don't see how else something like this -- a study of the past -- can help patients in the present. At worst, it can just get some of us thinking too much about things that don't really matter.

Here's the one statistic that does matter, as far as I am concerned: "Overall survival (OS) was superior in Era-2 versus Era-1 for all patients (5-year: 76.7% versus 67.4%, respectively)."

In other words, Rituxan has made our lives better, and our survival last longer.

That's not just a pitch for Rituxan (though goodness knows I'm happy to sing its praises). Era 2 in this study goes until 2009. We're in era 3 now. We're in the post-Rituxan era. The era of humanized monoclonal antibodies. The era of prohibitors. The era of targeted therapies.

If Rituxan did that much for us, as a group, imagine what all of this other awesome stuff will do for us. A cure? Maybe. But even if it means a way of controlling Follicular Lymphoma, taming it,  making it truly a chronic disease, that would be something pretty awesome, too.

So look at those statistics from the past if you're curious. But remember that stats from the past have not much to do with you in the present. 

And even less to do with your future.

Vorinostat! Zolinza!

Before I get into this, let me just say how great the name Zolinza is for a cancer drug. It's kind of hard to say it without smiling. Seems like there should automatically be an exclamation point after it, or maybe a few extra Zs at the beginning. Zzzzzolinza! I'd almost be happy to take it.

Oncologist: "Well, it looks like your Follicular Lymphoma has returned."
Me: "Gosh, doc, what are my options?"
Onc: "Well, there's Bendamustine. Or we could try Idelalisib. Or maybe.....Zzzzzolinza!"

And then the oncologist hands me a plate of guacamole and tortilla chips.

Awesome.

*********************

Anyway, a phase 2 study shows that Zolinza is effective for Follicular Lymphoma.

In a study soon to be published in the British Journal of Hematology, researchers gave Zolinza to 50 NHL patients, 39 of whom had Follicular Lymphoma, all of whom had relapsed form  a previous treatment (most of them had Rituxan + chemo).  About half of them showed a response, and the median Progression Free Survival was 20 months. There were some side effects, but for the most part, the results seem to justify a larger phase 3 study.

Zolinza is also known as Vorinostat. It has already been approved for relapsed Cutaneous T Cell Lymphoma (a skin-based lymphoma), so we have a pretty good idea of what we're dealing with. It has also been tried on some other blood diseases, and on small cell lung cancer.

Zolinza is another inhibitor, a treatment that doesn't aim to kill off cancer cells, but rather to stop a function that is crucial for the cancer cell's survival. In this case, it is a histone deacetylase inhibitor. It's kind of a cool mechanism to disrupt. In a nutshell, histone deacetylase is an enzyme necessary for DNA to function. It removes certain compounds from the DNA that keep it from wrapping up tightly. Since cancer cells rely on that rogue DNA to multiply, then interrupting that function will keep the cancer cells from multiplying.

As always, it's hard to predict where Zolinza will go from here, and what the results of the phase 3 trial will be. But I think it helps that this works through a mechanism that's different from others that are being explored or have been approved. If the trend really is to combine treatments in a way that attacks the lymphoma from a few different directions, then this one would certainly e worth exploring further.

Another potential arrow for the quiver.

Rituxan vs. Watching and Waiting in Follicular Lymphoma

The Lancet, a major British medical journal, offers the latest (though probably not the last) in the debate over Watching and Waiting versus Rituxan. This round goes to...Rituxan.

Researchers looked at 379 patients from Britain, Australia, New Zealand, Turkey, and Poland from 2004 to 2009. Patients were assigned to one of three groups: Watching and Wait; straight Rituxan as a first treatment; or Rituxan plus Rituxan Maintenance for 2 years.

Ritxuan Maintenance won  pretty handily.

Three years after being placed into the study, 46% of W&Wers did not need treatment. However, that's not great compared to the Rituxan group (78%) and the R-Maintenance group (88%).

Furthermore, they looked at Quality of Life, and found that, after 7 months, the R-Maintenance group beat both of the other two in "Mental Adjustment to Cancer" and "Illness Coping Style." (I'm not sure how those things are measured, though the names seem pretty self-explanatory.)

So the conclusion here is that Rituxan Maintenance might be the best option for newly diagnosed patients who are without symptoms and have low tumor burden, whether the measure is time to treatment or quality of life. The quality of life issue makes sense; there are probably lots of people who feel less anxiety when they are getting a treatment every two months. They must feel like they are taking some kind of action, which can be very comforting. I would still maintain that W & W is a choice, and not the best choice for some, and the quality of life issue would explain that. I was OK with not treating right away, and I know that's not emotionally possible for everyone. I'm not sure that part of the study really matters.

The time to treatment, however, is something to pay attention to. Again, using my own (very limited) experience, I would fall right within the W & W group, having taken two years to need treatment.

Would it have been different if I had done Rituxan Maintenance right away? We'll never know. However, if we step back and look at a bigger picture, I'm 6+ years since diagnosis and have only needed one course of treatment. If we looked at long-term follow-up of all of the patients in this study, will we find such a big difference six years out?

I'll admit that I want Watch and Wait to come out better in this debate, since that would validate my own choice.

That said, I think this study tilts things toward R-Maintenance a little, but it's still probably not enough to ditch Watch and Wait. Still too many proponents making good arguments based on available data (like Dr. Bruce Cheson) for this to be a real game changer.

But it certainly does give more fuel to the debate, and at the very least, should help validate the choice of R-Maintenance for those who make it.

Follicular Lymphoma Risk Factors?????

This piece is a couple of weeks old, and I really hesitate to post it (which is why I added all the questions marks), but the Non-Hodgkin's Lymphoma Center highlights a couple of recent studies that suggest some risk factors for Follicular Lymphoma.

Before we proceed, let me rem/ind you:


Even the best study of lymphoma risk factors is imperfect, and if there was a clear and definite link between certain factors and lymphoma, you would have heard about them two weeks ago on CNN and Fox, and not on this blog. So take what you read with a "Hmm, interesting," rather than a "Well, I guess I better go start smoking."

Yes, smoking: that's a risk factor. According to a study in the American Journal of Epidemiology, exposure to cigarette smoke as a child might increase the risk of Follicular Lymphoma, but might decrease the risk of Diffuse Large B Cell Lymphoma.

And in a study from the Annals of Oncology, it was found that Body Mass Index (a measure of height and weight that can identify obesity) showed that there is no association between BMI and lymphoma survival. In other words, fat people didn't fare any worse than skinny people when they get lymphoma. This seems to contradict some previous research.

So, good news for me on the obesity -- I haven't run in about 3 months. The smoking thing? Maybe I can rationalize that one as reducing my risk of transforming? After all, exposure to smoking might give you Follicular Lymphoma, but not DLBCL, right?

No, no, no. Of course not.

And that's the problem with studies like this. It's too easy to make false associations. And unfortunately, that often happens in media reports about cancer risk factors. Thank goodness, this particular report didn't do that, and they deserve all credit for that.

But consider this post a warning about just that sort of thing. It's too easy to get excited about good things you read, and horrified about bad things. Especially during those times when we're emotionally vulnerable, which happens to all of us. We need to remember to just slow down. Relax. Smoke a cigarette. Eat a whole box of Twinkies. It's not like it's going to kill you or anything.....

Seriously -- read widely, but critically. Don't just pick and choose the stuff that tells you what you want to hear. At the very least, if you come across something that gets you overly excited or depressed, at least talk to your doctor.

And if she tells you that you have good reason to worry, or to get excited, than let me know. I'll be happy to share it with everyone.

Cure for Cancer on a Smartphone

Cancer Research UK is sponsoring a smartphone game called "Play to Cure: Genes in Space." It allows players to decode genetic material while they play the game, "blasting through space."

Each time they play the game, they analyze the DNA of one chromosome. Apparently, players have done the analysis work in one month that it would normally take scientists six months to do. Apparently, human eyes are required to find patterns, which is how the game works.

I read about this just a couple of weeks after I have an orthopedic surgeon basically play a video game while he does arthroscopic surgery on my shoulder, working a couple of joysticks while he watches a monitor. I think I should have stayed a science major. It all sounds like they all have a blast.

Anyway, here's the story about the smartphone game. Video included!

And it's available on iTunes and Google Play for free!

Idelalisib

The medical journal Blood published three articles recently on Idelalisib, formerly known as CAL 101 and as GS-1101. One dealt with the remarkable success that Idelalisib has shown on CLL; another on the somewhat less successful attempts to treat MCL; and a third that was moderately successful in treating indolent NHL, including Follicular Lymphoma. The results come from a phase I clinical trial.

Idelalisib is a kinase inhibitor (as you know if you've been paying attention to these things). It specifically targets the P13 enzyme, which B cells need to survive. So inhibiting or blocking it will kill off the cancer cells.

The indolent NHL group involved 64 patients, all of whom had already had at least one previous treatment (and some as many as 10). Because this was a phase 1 trial, it could be considered a big experiment, with researchers asking first, will it work?, and second, is it safe? As such, patients were given 8 different variations on how many (it is taken as a pill) and how much of the treatment taken.

The results were decent: 47% had a response, with one achieving a complete response. The median duration of response was a little more than 18 months, and side effects were for the most part mild to moderate.

While 47% doesn't seem all that astounding, it's important to remember that this is a phase 1 study, and that's good enough to justify a phase 2, which will be more refined than the general phase 1 study. It will likely involve a specific number and strength for the dose, based on what worked best. In addition, according to the lead researcher, given the number of previous treatments that the patients had, the results were pretty remarkable.

So we have further evidence that Idelalisib might be a keeper.We're going to hear a lot more about this treatment over the next year, I think.

Managing Follicular Lymphoma: State of the Art

From the most recent issue of the journal Leukemia: "How We Manage Follicular Lymphoma."

Yes, Leukemia also publishes research on "allied diseases," like lymphoma. They are also awesome, allowing their articles to be viewed online, which is why we get to read this one.

The "we" in the title is Dr. Wolfgang Hiddemann from the university of Munich, and our own Lymphoma Rock Star Dr. Bruce Cheson.

Nothing really new here, which is fine: Hiddemann and Cheson are describing what they typically do for patients at different stages of Follicular Lymphoma. So while it isn't a report on new research, it is a report on what works now and what two specialists think might work in the near future. So this is about as "state of the art" a discussion of Follicular Lymphoma as you are likely to find anywhere for today.

It's also pretty accessible, so you don't need a lot of commentary from me. But I'll give you a summary, anyway.

The good doctors look first at Stage 1 and 2 Follicular Lymphoma, and point out that while radiation therapy is often adequate for these patients, it is used less than one-third of the time. They also make a push for better care in staging, which has an impact on patients in this group.

In looking at "advanced stage" (3 and 4, which is where most of us fall), they divide us into two groups: those with low tumor burden and without symptoms, and those with high tumor burden and some symptoms. These two types obviously present different problems to be solved.

First, for low burden/no symptoms, they confirm that watching and waiting is still a valid approach. They also discuss straight Rituxan as an initial treatment, as well as Rituxan Maintenance. And then they compare the two approaches, something Cheson has done several times before. And as he has done before, Cheson still comes out in favor of watching and waiting, on the basis that there is still no evidence that immediate treatment gives any better results.

For those with symptoms and/or bulky disease, they review the options available: R plus chemo (CHOP and Bendamustine continue to be the chemos of choice). And after remission, there are further options: RadioImmunoTherapy, Auto Stem Cell Transplants, R-Maintenance, and all of the controversies that go along with those options.

Next, the doctors review "New Agents," and their excitement is evident. They discuss new CD20 antibodies (possible replacements for Rituxan, such as Obinutuzumab/GA 101); antibodies that target proteins other than CD20, such as Epratuzumab and Galiximab; and some treatments that target pathways, including the various kinase inhibitors that are getting people excited lately. Finally, they discuss Lenalidomide, or Revlimid, and its effectiveness when combined with Rituxan (R-squared).

Interestingly, they also include a section on how they feel current treatments could be used more effectively. Their discussion includes better ways for using the FLIPI index, and PET scans.

In their conclusion, they discuss not only the changes in treatment options that we have seen, but also the ways those changes have challenged our assumptions about Follicular Lymphoma. It's a "moving target," to use their words, but it seems to me that the challenges that researchers face will only improve our future prospects.

Definitely an article worth reading if you want to see where we are with Follicular Lymphoma, based on current research.

Post-Surgery Follow-Up

I saw the shoulder surgeon today. Things look good.

The incisions are healing very nicely. (Arthroscopic surgery is a remarkable thing -- three small holes, now covered with band-aids.)

I'm allowed to shower on my own now, without assistance from my wife. (I'll miss her....)

And I have some new exercises to do, which he held off having me do right away. So he's confident that things are at least beginning to heal.

He also showed me some pictures from the surgery. As I said, arthroscopy is a pretty remarkable thing. He managed to reconstruct things and sew them all back together.

It's all going to taker some time, of course, and lots of hard work to get things back to normal, or close to normal, but it was nice to have some confirmation that things are on track.

Back to Lymphoma stuff soon

Subcutaneous Rituxan for Follicular Lymphoma

From the British journal Lancet Oncology comes the article "Subcutaneous Rituximab Noninferior to IV Formulation in Follicular Lymphoma," a look at whether or not Rituxan could be as effective if given as an injection rather than as an IV.

It seems that it can.

The study is part of a multinational study of Follicular Lymphoma called the SABRINA study. The goal is to determine if the injected Rituxan would stay in the blood in concentrations similar to those of the traditional IV. Patients were split into 2 groups. Both were given either CHOP or CVP, but one group had Rituxan by IV, and the other by injection. The chemo was given for 8 cycles, and at the end, patients who had a response were given Maintenance Rituxan (again, either IV or injection) every 8 weeks.

The two groups were tested to see if the concentrations of Rituxan in their blood were comparable. It's possible that the less concentrated, slower dose of an IV would be more effective, and would cause fewer problems, than the rush of a more concentrated injection.

But the results showed that the two methods were indeed comparable. Their next step is to measure safety and effectiveness in more detail.

As the intro to the Summary points out, the researchers are hoping that the injection method will "improve convenience and save health-care resources." As those of us who have had Rituxan are aware, four hours in a chair, especially if the treatment is weekly, is not all that convenient, and can take up the time of a nurse or two. Maybe an injection can be a small step in reducing costs, and in making life just a tad easier for Follicular Lymphoma patients who are receiving treatment.

Certainly worth keeping an eye on, particularly as this might be a method for delivering some of those other Monoclonal Antibodies that are being developed, too.

Improved RadioImmunoTherapy for Follicular Lymphoma?

I need to get back to my blog. Shoulder sling or not, I've got to get on with my life. As I said, you know things are going great when you can distract yourself by writing about cancer....

I'll probably do a little less commentary than I'd like, but that will give me something to build up to.

This news is almost a couple of weeks old now, but it's exciting. Researchers at the University of Manchester in England are looking into RadioImmunoTherapy as a front-line treatment for Follicular Lymphoma. Zevalin has been approved as for use in FL after a first treatment has stopped working, and as a way to extend a successful first treatment. This study is showing that we can skip the Rituxan or CHOP and just get right to the RIT.

The study was published in the Journal of Clinical Oncology (I still haven't had a chance to read the full article). What makes this approach special is that the researchers gave the RIT in two smaller doses, rather than one big one. This seemed to have allowed it to better penetrate larger tumors (the patients in the study had bulky disease, or larger tumors), and also seemed to cut down on side effects.

And it worked well: 94.4% of the 72 patients had a response, and 69.4% had a Complete Response. Those are some dang good numbers.

Are they good enough? I hope so, but it will still be a struggle to get people to recognize just how great RIT is. Bexxar is gone, and one of the hurdles that Zevalin faces is the difficulty that comes with administering it. (It can't be done in an oncologist's office, but rather needs a team of nuclear medicine specialists to do it.) Hard enough to get it all done once; will it be even harder to accept if all that effort has to be made twice? At the very least, it won't make it any easier.

Sorry for the negative slant on this. I guess the positive look on it is that it gives us one more way of considering how to use RIT effectively.

I'll try to write something sunnier next time. Or not wait until the Percocet is almost worn off....

Recovering

Well, the shoulder surgery is done, my Percocet haze is lifting, and I finally got to take a shower today. So I've got a few things going for me. Which is nice.

The surgery seems like it was a success, even though the surgeon told my wife "It was a mess in there." He was able to do the repair, and now we just wait to see if it holds.

I'm already sick of sitting around and watching tv.

I think my wife is getting tired of me pacing around the house.

The dog wants to know why I'm home all the time but not playing with her. Also, I think she enjoyed me pre-shower. My scent is much less interesting now.

My kids have been pretty good about helping out. My wife has been an absolute amgel about taking care of me.

Not much else to report. I'll post something Follicular Lymphoma-related soon. I could use the distraction.

(You know things are awesome when you can use cancer as a distraction....)

And thanks for the well-wishes. More sometime this week.