Watching and waiting?

I'm behind on this, like I'm behind on everything these days: Nice article from the June 9 issue of Blood, called "Is watch and wait still acceptable for patients with low-grade follicular lymphoma?"

I haven't written about watching and waiting for a while, because I was tired of reading articles that said they had the answer about whether or not it was still a good strategy, and then it turned out that they really didn't have the answer. Obviously, I have my thoughts on watching and waiting -- I think it's an acceptable thing, and I did it for two years, and I would make that same choice today.

I'm not sure there really is a definitive answer here, either, but I'm not sure that they are trying to give us one. It's more a review article, looking at what we know about Follicular Lymphoma and whether or not that can tell us anything about watching and waiting.

And there's lots that we know.

We know that median survival for FL has gone up over the years, and that Rituxan probably has something to do with that. There are some experts who say that we shouldn't bother with watching and waiting because one of the reasons for it was because it let us hold off doing any kind of treatment. When there are limited treatments, and they have nasty side effects, it's better to hold off on treatment for as long as possible. But now that we have Rituxan, plus more good treatments on the way, may be we don't need watch and wait anymore?

We also know from several studies that patients who do watch and wait have no real difference in Overall Survival. Some studies show small differences in things like time to progression -- how soon a patient's disease will grow to the point where treatment is needed. But no survival difference. And if that's the case, maybe watching and waiting is OK to do? As my dear Dr. R told me, it's better to do no harm, and as nothing was changing, observation was a fine strategy.

We also know that major cancer organizations' guidelines call say that watching and waiting is acceptable for certain FL patients -- basically those who don't have symptoms, and have a slow-growing form of FL. You'll find that advice in guidelines for groups from the U.S., the U.K., Canada, Italy, and Europe at large.

What would be great, say the authors, is if we had a biomarker that told us that watching and waiting was the best choice -- some kind of gene or protein or enzyme that let us know that the patient would not progress quickly. Amen to that. It would be wonderful to know how this messed up disease is going to behave in the future. But so far, we aren't there.

I'm pleased that the authors at least nod toward the emotional aspects of watching and waiting, giving it one sentence: "A physician’s enthusiasm for watch and wait in this setting should not override the patient’s preference for therapy based on anxiety about not treating a known cancer."

But I'd sure like to see more than one sentence.

I've said before that Follicular Lymphoma is as much an emotional disease as a physical one. It has to be -- as patients, we have more time to think, and for most of us, at least at some point, those thoughts are going to be negative. Especially at the time we need to make that decision -- soon after we get the news that we have cancer. You can show us all kinds of charts and statistics about Overall Survival rates. But our thinking brains aren't working at that point. It's our feeling brains that are making the decisions for us. We need someone who knows how to talk to us at that point.

I'd like to see an article aimed at oncologists that talks about how to consider a patient's emotional state when describing watching and waiting as a treatment option. More than a sentence -- I want a whole article.

So, yeah, in the end, this review article does a nice job of laying out what we know about FL and watching and waiting. But it still isn't giving me any answers. We need to write about watching and waiting in a new way. Someone needs to write that article.

(Maybe it will be me......)

Long Live Zevalin

I'm not getting through the ASCO posts as quickly as I have wanted to. There's some interesting stuff, but nothing that has really blown anyone away -- at least not anything dealing with Follicular Lymphoma.

But here's another good one: "Single center experience of 90Y-Ibritumomab tiuxetan in the older population with non-hodgkin lymphoma."

90Y-Ibritumomab tiuxetan is better known as Zevalin, the RadioImmunoTherapy treatment that has never gotten the love from the oncology community that it has deserved. This study looked at patients from one treatment center who were given Zevalin as a consolidation treatment (a treatment given soon after an initial treatment as a way of trying to clean up more of the cancer) or a salvage treatment (a follow-up treatment after one that didn't work). The patients were older, and the results were very good: an 89% Overall Response Rate, with 36% of patients in the consoloidation group going from a Partial Response in their first treatment to a Complete Response with the Zevalin; and 55% of patients responding in the salvage group.

Great numbers, right?

It's one more study in a long line of studies that show how effective Zevalin can be for NHL, and FL in particular.

So why is there no love for Zevalin?

Lots of reasons, but one of the biggest is that it's tough to find someone who can or will administer Zevalin. That's been the case from the beginning, for reasons that have nothing to do with its effectiveness as a treatment.

And now, Zevalin might be gone for good.

Here is a link for an excellent article from Jamie Reno, a great writer and Lymphoma Rock Star in his own right. He's a Follicular Lymphoma survivor himself -- someone who benefit from Zevalin. He describes the problems that Zevalin is facing, and why it might be going away (again, it has nothing to do with its effectiveness).

The article quotes Betsy De Parry, another author and FL survivor, thanks to Zevalin, and Karl Schwartz, President of Patients Against Lymphoma/Lymphomation -- all the Lymphoma Rock Star advocates are getting in on this one!

And we need them to. We all need to get in on this one. I always use the phrase "another arrow in the quiver," which is the phrase that Dr. C used -- the lymphoma specialist I saw a few days after I was diagnosed. It means another weapon that we have in reserve. For FL patients, we have a lot of weapons, and better ones on the way.

But it still hurts to think that a really good arrow might be taken away for good. Let's hope that doesn't happen, and let's thank the folks who are trying to make sure that it doesn't.

ASCO: Marriage and Blood Cancers

Another review from the ASCO conference. I found this fascinating.

Apparently, research has shown that cancer patients with solid tumors have a higher Overall Survival when they are married, compared to unmarried patients. So researchers asked, is the same thing true for patients with blood cancers?

The answer was presented in "Impact of marital status on the survival of patients with hematologic malignancies reported to the California Cancer Registry." Researchers looked at records of over 58,000 patients in California with blood cancer, diagnosed between 2000 and 2009. Of course, Follicular Lymphoma patients were included.

The researchers did some statistical analysis on all those records, and determined how marriage status affected Overall Survival, adjusted for age, sex, race/ethnicity, treatment, insurance status, and neighborhood socioeconomic status.

In almost every category, married blood cancer patients had a higher OS than unmarried patients. The highest OS was among married patients with higher socioeconomic status, for certain blood cancers, including Follicular Lymphoma.

So what it is about being married that potentially leads to higher OS rates? (And it's worth remembering that all of this involves statistical analysis, and marital status is no guarantee of anything for any individual patients)

I guess the answer that makes the most sense is that being married means you most likely have easy access to a support system -- emotional support, physical support, spiritual support. I know from my own experience that dealing with my diagnosis, my watching and waiting, and my treatment were all a heck of a lot easier because of my wife. In fact (I've told this story a lot) my first few weeks after diagnosis were hell because I refused to rely on my wife. It was only after I used that support that things got easier for me emotionally.

Now that certainly doesn't mean that unmarried patients won't do well. But it does seem to confirm that people with a support system have an easier time. The researchers suggest there should be more research done in this area, looking at some other factors affect unmarried patients -- things like social support, sticking with a treatment, and healthy lifestyles (all things that are probably helped by having a spouse who reminds you to take your medicine and eat your vegetables, and gives you a hug every now and then).

I think the big lesson here is that our lives are made easier with some kind of support, whether it's from a spouse, a family member, or a good friend. Cancer is way too hard to handle by yourself.

ASCO: Velcade, Bendamustine, and Rituxan

Another good one from ASCO: "Effect of bortezomib on complete remission (CR) rate when added to bendamustine-rituximab (BR) in previously untreated high-risk (HR) follicular lymphoma (FL): A randomized phase II trial of the ECOG-ACRIN Cancer Research Group (E2408)."

I've written about combination therapies before -- the idea that one single treatment probably isn't going to cure Follicular Lymphoma (or most types of cancer). Cancer is a sneaky thing, always finding ways around our attempts to stop it. So combinations that attack the cancer in different ways might have a better chance of stopping it.

And this ASCO piece is about as combination-y as you can get. It's almost like the researchers looked at every FL treatment that has work in the last 5 years and tried to find a way to work it in. It's one big FL-killing stew.

Basically, they added Velcade (Bortezomib) to the already-successful combination of Bendamustine and Rituxan. Then, for good measure, they added Lenalidomide (Revlimid) to Ritixan Maintenance (making R-Squared Maintenance). Like I said -- if something has worked in the last few years, they threw it in there.

The study looked at 222 untreated FL patients who were considered "high risk," with a high FLIP score or high tumor burden. They were divided into 3 groups: one was given Bendamustine + Rituxan (BR) and then Rituxan Maintenance (RM). The second had BR + Velcade, and then RM. The third got BR + Velcade, and then RM + Revlimid.

The Overall Response Rate (complete or partial response) for BR was 90%, and for BR + Velcade, it was 91%. Pretty much the same.

But the Complete Response rates were very different: BR was 58%, but BR + Velcade was 74%. That's a pretty amazing difference.The researchers called it "significantly superior."

No word on how the Revlimid affected things, though the conclusion does say that more follow-up is needed to determine whether the Revlimid helps with prologing that CR.

So I'd call this good news. There were certainly some side effects (that's the problem with combining so many treatments -- you combine all of the bad stuff that goes with it, too. And there's always at least some bad stuff).

But a 74% CR rate says something about how well that combination is cutting off cancer's escape routes. This might not be THE combination we're looking for, but if nothing else, it gives us more evidence that the general strategy of combining treatments holds a lot of promise, and we're going to keep seeing more of it in the future.

ASCO: Vitamin D and Follicular Lymphoma

Here we go! ASCO research!

Before we get into this, it's worth reminding everyone of whet we're dealing with here. ASCO, the annual meeting of The American Society of Clinical Oncology, is a very important place for cancer researchers to present their findings to other oncologists. However, it is NOT the place where they present their final results. They may get feedback from other oncologists, and they may get people excited about their research, but it needs to go through a peer review process to really be trusted. That's when other experts in their field go through their results and give them a stamp of approval, so they can be published in a medical journal.

That's important to remember. We can get excited about ASCO stuff, but not officially excited.

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Up first: "Association of Vitamin D Insufficiency with Inferior Prognosis in Follicular Lymphoma."

This research builds on work that was presented at ASCO in 2012, and then was eventually peer reviewed and published in the Journal of Clinical Oncology in 2015. In the earlier work, researchers found that low levels of Vitamin D in patients who had been given Rituxan + chemo resulted in lower Overall Survival. (Of course, that's a statistical analysis, and some patients did not have a lower OS.)

The research being reported on this year asks if low Vitamin D levels are a problem for ALL Follicular Lymphoma patients, no matter what treatments they've had, and not just the R + chemo patients. (It's a recognition that maybe it's the treatment that needs Vitamin D.)

They looked at 659 FL patients, hoping to predict whether low Vitamin D would be able to predict Event Free Survival at 12 Months (that is, they the patient went a year without the FL coming back or getting worse), Overall Survival, and Lymphoma-Specific Survival (that is, that their death was caused by their lymphoma).

They found that 34% of the patients had low Vitamin D levels, and of the 659 patients they looked at, there were 389 events (lymphoma returned or got worse), and 82 deaths (46 due to lymphoma).

For the whole group, low Vitamin D was associated with lower Event Free Survival, Overall Survival, and Lymphoma-Specific Survival.

This was also true for the specific patients who had Rituxan + Chemotherapy.
For patients who were on Watch and Wait, and who take treatments other than Rituxan or R + Chemo, low Vitamin D was associated with lower Overall Survival and Event-Free Survival.
Researchers could not make associations between Low Vitamin D and other treatment groups that were statistically significant.

Their conclusion is that, because there seems to be a connection between Overall Survival and low Vitamin D levels, this is something worth looking into.

Now, personally, I take a Vitamin D supplement every day. A few years ago, I had read enough to suggest that low Vitamin D might cause a bunch of problems, and since I don't stay out in the sun much, I could probably use the extra D. It's easy to find, costs me about $6 a month, and won't hurt if I take it in moderation (and with my doctor's permission).


That certainly doesn't mean that Vitamin D is the reason my lymphoma has stayed pretty stable. I just can't know that. I'm not one to believe in miracle cures, which is why I like seeing research like this. I will keep looking for their peer-reviewed follow-up, and any other research on this subject.

In the meantime, remember that any supplement should only be taken after talking with your doctor. Even Vitamin D has some potential complications for lymphoma patients.

But we can still be hopeful. More ASCO news soon.

Genes (and Cancer)

It's that time of year -- ASCO is just around the corner! The American Society of Clinical Oncology conference will take place June 3-7 in Chicago. There is usually some good stuff that comes out of ASCO; researchers sometimes announce early results from clinical trials. Sometimes those results are late in the game, just before they are sent out for peer review and publication in medical and science journals. Others are very early -- maybe a new treatment tried out on just a few patients. But there's almost alays a few things to be hopeful about.

As I have done for the last few years, my plan is to look at abstracts related to Follicular Lymphoma, and report on the things that seem interesting to me.

Unfortunately, I haven't even had a chance to look at the ASCO web site yet. It's been busy at work, and my kids are in the last few desperate weeks of school. To top it all off, my boss has left the country for six weeks and put me in charge. Ugh. It's been one day and I've been going non-stop.

So I'll get a chance to slow down and catch my breath and read some ASCO abstracts soon.

In the meantime, I'll share with you a fascinating interview with Dr. Siddhartha Mukherjee, the oncologist who wrote Emperor of All Maladies: A Biography of Cancer, a fantastic book about cancer and its treatments. Very readable and very informative.

Dr. Mukherjee has a new book out, called The Gene: An Intimate History. The book focuses on what we know about genes -- knowledge that has increased at an incredible pace in the last few years. The interview (which was on the NPR radio show Fresh Air, and lasts about 37 minutes long) does talk about cancer, and how our understanding of genes has given even more hope for cures (or maybe just treating some cancers as long-term chronic diseases). But he also gets into some of the potential ethical dangers of knowing so much about how genes contribute to our lives.

Great interview, and a fascinating-sounding book. It's on my summer reading list.

Come back soon for some ASCO news.