Some Articles on Follicular Lymphoma

If you're enough of a Cancer Nerd that you like reading medical journal articles, then the most recent issue of Blood is just what you have been waiting for. They have a special section that reviews Indolent Lymphomas, including Follicular Lymphoma. There is one article devoted to FL, and another that looks at Stem Cell Transplants, which also focuses a lot on FL (along with other slow-growing lymphomas).

If you're not enough of a Cancer Nerd to read medical journal articles, then I'll try to hit some highlights for you.

The Review Series starts off with an introduction called "The Paradox of Indolent B-Cell Lymphoma."

A Paradox is something that seems to contradict itself, even though both parts of it are true. Like watching and waiting: we don't actively treat our cancer, but we might be better off doing nothing. That's a paradox -- everyone knows that not getting aggressive treatment for cancer isn't good, and yet....

Follicular Lymphoma is full of paradoxes. Sometimes I think about them, or try to explain them to people, and I realize just how messed up and weird a cancer it really is. Like

• It's a slow-growing disease, and maybe doesn't need to be treated for a long time, maybe never. Which is good. But it's also incurable. Which is bad.
• It's a quiet disease, so quiet we can almost forget about it. That's good. But that quiet can be a problem if it transforms, and you're not paying close attention to it. That's bad.
• We have a good bunch of treatments that work well, with more on the way. That's good. But there are so many treatments that work well, we don't have an protocol that we agree on. Some oncologists say to watch and wait, while others, for the same patient, might suggest Bendamustine, or CHOP, or even CVP. No agreement. That's less good.
• Treatments often work for a long time. That's good. But they can work for so long, and there are so many options, that it's hard to construct any kind of clinical trial that looks at sequencing of treatments -- comparing how well a large group of patients do when trying a certain treatments after other treatments. That's not as good.

Isn't it fun to be part of such a weird disease, gang?

But even with all of those paradoxes and contradictions, we're still doing OK. The Introduction article says our median overall survival is probably greater than 12-15 years. When I was first diagnosed in 2008, Wikipedia said it was 8-10 years. So something is going right for us.

(I'm pretty sure that something is Rituxan....)

And that's kind of the theme of the main review article for FL, "Follicular Lymphoma: Evolving Therapeutic Strategies." It's a review article, meaning it is reviewing what we know about FL -- not really adding anything new. It discusses what we know about the Biology of FL, and how gene mutations lead to Follicular Lymphoma; and how the microenvironment (the stuff that surrounds the cancer cells, noy just the cancer cells themselves) play a role in FL growing and thriving; the kind of prognostic tools used to evaluate it (various FLIPIs, including the m7-FLIPI for more aggressive FLs). And it finally looks at transformation, the Big Monster We Fear. Good news there -- recent studies have shown a longer Overall Survival -- more than 5 years -- than we had previously thought.

The article then looks at some of the treatment options available for FL patients at different stages. It is summarized in this neat graphic:



It's a nice flow-chart, maybe something worth thinking as you consider different options. But be warned -- it's not a substitute for a conversation with your oncologist, and it doesn't really mention specific treatments. It certainly doesn't mention treatments available in clinical trials. We don't want to leave them out, do we?

The article does get into some more specifics of different treatments, their effectiveness, and what they might be good for. So you might be forced to read this article anyway.

Finally, the Blood issue has an article called "The Role of Autologous and Allogeneic Stem Cell Transplantation in the Management of Indolent B-cell Lymphoma." Like the FL article, this is a review article, looking at what we already know about SCTs, rather than offering anything new. I wrote about Stem Cell Transplants last month, and the basics remain the same: Auto SCTs are safer, but not always as effective. Allo SCTs might offer a cure, but can have some dangerous side effects like Host-vs-Graft Disease. The article goes into more detail about what we know and don't know.

What I know is this: We have a weird, messed-up cancer. But in all of those paradoxes, even if we say something is bad, or less than good, there is still plenty of good -- for many of us, it's a disease without symptoms that allows us to live our lives (at least our physical lives) in a fairly normal way, and we have lots of treatment options to try. And that's all good.

So we can keep our focus on that until we need to think about the less-than-good stuff.

Individualized Rituxan?

The San Diego Union-Tribune published a very interesting article last week called "Individualized Lymphoma Therapy May Be Resurrected." I think the Tribune was especially interested in this because it involves work that was done years ago by a San Diego company. (And before I go any further, I have to thank Patients Against Lymphoma, who linked this article on their Facebook page.)

The article focuses on work by Dr. Ronald Levy from Stanford University, who was important in the development of Rituxan. Years before that, Dr. Levy was part of a project that developed a monoclonal antibody that was individualized for each patient.

If you've been reading for a long time, you know I've been fascinated by individualized treatments, like the vaccines that come around every once in a while (but still haven't quite taken off yet). They recognize that while a disease like Follicular Lymphoma is a certain disease with certain characteristics, every patient's will be just a little bit different. So a treatment that can deal with those little differences and target someone's own individual cancer situation would be very valuable.

Now consider Rituxan, the monoclonal antibody that changed everything -- making other treatments better and extending our lives.

Now bring them together. Sounds good, doesn't it?

A version of that treatment was put into trial in 1981, for 50 patients. One of those 50 went into remission for 32 years, and died at age 99, with no lymphoma. (Are you reading, Marie?) Of course, there's nothing in the article about the other 49 patients, but there was enough success to make it worth looking into again.

here's how it worked: Rituxan, as we know, targets a particular protein (CD20) on B cells, the immune cells that turn cancerous for us with FL. Rituxan targets ALL B cells, not just the cancery ones, so some people can have immune system issues for a while after they have Rituxan. (Not too severe -- it doesn't wipe out the entire immune system the way a Stem Cell Transplant would.)

If there was a way to make Rituxan focus only on cancer cells, that would be great. But that would involve the kind of individualization that can get very expensive.

That's where Dr. Levy and his team come in. By using something called a Peptibody, they can target individual cancer cells for each patient. Unlike some of the lymphoma vaccines, that depend of manipulating and then growing a patient's own immune cells to fight the cancer, the Peptibodies approach relies on a "library" of peptides, which are small sections of proteins. By going through the library and matching a peptide to the patient's individual cancer cells, and then attaching it to a Rituxan molecule, the Rituxan can more easily target the cancer.

Think of it this way -- I just heard a radio advertisement for a windshield replacement company that bragged about having 160,000 windshields in their warehouse. So we'll go with that comparison.

Imagine you broke your car's windshield, and needed a replacement. You could call Joseph's Artisan Windshields, and Joe would come to your house, measure your car, and go back to his artisan studio, where he would melt some glass in his furnace and with a large tube, blow and shape a windshield that fits your car perfectly, because it was made only for your individual car. It will account for that bump near the roof where your kid's baseball hit it, and that dip from where the moulding melted when your other nerdy kid left a magnifying glass there. Perfect fit. Of course, that perfect fit from the artisan shop took 5 weeks and cost you $6000. (And your insurance company wouldn't pay for it.)

That's the individualized vaccines that have been developed in the past. They might work well, because they are made just for you. But they take a long time and are very expensive to create.

Now imagine that instead, you call Joey's Glass Replacement. You give them the make and model and year of your car, they go to their warehouse of 160,000 replacement windshields, and they find the one that is probably going to fit. They add a little extra moulding and bump up the dent, and they make it fit. It's doe in 2 hours, not 5 weeks, and it costs $200. They're cheap because they aren't made one at a time in a glass blowing studio, but in a factory that churns them out by the hundreds.

And that, of course, is the new model. Instead of making it exactly to your car (or cancer), it goes through a bunch that are already made and finds the one that is most likely to work. It will still be individualized to you and your cancer (nobody is going to try to put a big Escalade windshield on your little Fiat), but not quite as individualized as the older model. And unlike the older vaccine model, which had to wait for live cells to grow, the peptides are chains of proteins that can be made quickly and cheaply by chemical means.

The peptide/Rituxan combo kills cancer cells on its own, but also helps immune cells called macrophages eat up those cancer cells, too.

So what you end up with is the effectiveness of Rituxan with the individualization of a vaccine.

The trick here is going to make it work well enough to justify the cost, even if the cost would be a lot less than a vaccine. Rituxan is already pretty inexpensive, compared to a lot of other treatments, given how effective it is, and its patent is expiring soon, so generic versions will be even more inexpensive. Trials will have to show that the extra cost of adding peptides will be worth it because it will work even better than Rituxan on its own (or better than standard chemos, or other newer treatments).

It's possible that this could come to clinical trials in a year. we'll have to see. A better version of Rituxan has been hard to find. Maybe this will be the one? If you're going to bet on someone, Dr. Ronald Levy is a true Lymphoma Rock Star -- could be a pretty good bet.

(Read that Tribune article. Links to  Dr. Levy's lab study results, and a podcast in which he talks about the treatment.)