Another Failed Vaccine for Follicular Lymphoma

The Journal of Clinical Oncology gave us bad news last week: another attempt at a vaccine for Follicular Lymphoma has failed.

I've been trying to wrap my mind around this one for a few days, and I think I'm getting caught up in some of the details.  For example, the study used something called a Keyhole Limpet Hemocyanin, or KLH, which is a protein found in the "blood" of the limpet, a kind of snail that lives off the coast of California. KLH is used in developing antibodies. It's all pretty straightforward, but every time I see "limpet," I can't help but think of the movie The Incredible Mister Limpet with Don Knotts, which I saw about a hundred times when I was a kid because it was Saturday afternoon and there were only 5 channels and there was nothing else good on. He plays a wimpy guy who loves fish, and he wishes he could be one, and then the movie turns into a cartoon, and then he helps us win World War II. I haven't seen it in years. It's all very distracting when I'm trying to read a complicated medical journal article.

 And so, shoving Don Knotts out of my head, we can move on:

As I've said before, I've been very interested in vaccines for Follicular Lymphoma because a few days after I was diagnosed, I saw a Lymphoma specialist who mentioned some treatments in the pipeline, and one that he was particularly excited about was the vaccine. He didn't mean a true vaccine, but an injection that stimulates the immune system to fight off cancer.

It's been over six years now, and the news about vaccines continues to be mixed, at best.

BiovaxID, for example, is based on the idea that each of us has a unique "idiotype" on our cancer cells. BiovaxID works by taking a sample of an individual patient's cancer cells and training the body to recognize and attack them. (How they do that is complicated -- it's where The Incredible Mister limpet comes in.) The results for BiovaxID have been mixed. Pretty good, but not really good enough -- the FDA turned down the request for accelerated approval and asked for an additional trial because they hadn't been able to enroll enough people. But its less-than-ideal numbers actually yielded decent results.

The recent Journal of Clinical Oncology article looked at a different Follicular Lymphoma vaccine, MyVax.

Really, this isn't about the effectiveness of MyVax. The FDA turned down MyVax in 2008 because a phase 3 trial showed that patients who were receiving the treatment weren't any better off than the patients in the control group, as measured by Progression Free Survival. The company that manufactured MyVax declared bankruptcy, and the vaccine hasn't been made since then.

What the JOC article does is provide an update on some older data. How old? The patients in the trial received CVP without Rituxan. (There's a cancer nerd joke to be made in there somewhere. Probably funnier than a Don Knotts movie, if anyone cares to pursue it.)

So that part of the data isn't really new. We've known that for 6 years. What is new is that a group of patients who received the MyVax vaccine -- 41% of them -- had a response, and it was significant. In other words, not everyone who received the vaccine did well, but those who did well did really well.

This raises some questions. What was it about that group of patients that made them respond so well? In a separate article from the same issue of the journal, Dr. John Gribben speculates on some of the reasons (while mostly confirming that vaccines don't seem to work). Maybe there's something about the microenvironment of the cancer cells that makes these patients special? It's possible that the patients had different FLIPI marks and weren't really comparable.

So, as I said, this whole thing was tough to wrap my mind around. And it wasn't just because of Don Knotts. As much as Dr. Gribben makes it clear that this trial was a failure ("This is the third randomized trial to report on the use of different approaches to examine the impact of Id vaccine and adds to the data suggesting that there is little evidence of a beneficial effect of Id vaccine in patients with FL"), there are little bits of hope shining through in spots, enough to make me believe that maybe this isn't dead yet.

And it's not just the memory of speaking with Dr. C six years ago. Almost every commentary about Follicular Lymphoma vaccines starts with some statement about how promising the idea has been, and ends with frustration about why the promise hasn't come true yet. So there's got to be something there. Maybe with all of this other work in immunotherapy going on, the missing piece will be found.

So I'm hanging on to hope. In the meantime, there are plenty of other things to be excited about, right?

Happy Mother's Day

I'd like to wish all of you Moms a Happy Mother's Day.

I have to say, I've encountered some pretty spectacular moms in the last six years as I've been on my cancer journey.

I've seen some moms in my support group who have had children of their own, adult children and actual kids, and seen their determination in doing what they can to protect their babies. Researching treatments. Fighting with doctors and insurance companies. Providing a shoulder to cry on.

I've seen nurses who have kids of their own, who treat patients like their own kids. (My wife says once you become a parent to one child, you become a parent to the world.)

I've seen my wife worry about our own kids and show me her worry. I've seen her worry and hide it. And I've seen her be a rock when I was worried. Mostly, I've seen her be a rock.

And I saw my own mom's worries about me. Those worries, of course, wouldn't stop her from siting with me all morning for a Rituxan treatment. It certainly wasn't fair that she had to go through it all with me, but it sure didn't stop her from doing it.

If you've ever seen a mom get mad at a coach for not playing her kid, and seen the anger in her eyes, then you can imagine a mom up against cancer -- her own, her partner's, her child's. Just multiply that anger by a thousand, and add a healthy dose of determination.

So that's what I'm feeling today. Sorry for moms whose lives have been touched (and sometimes slapped hard) by cancer, and gratitude that you were there despite it.

I hope you've all had a very happy day.

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I think I linked to this during my first Mother's Day with lymphoma six years ago, but took it down because the YouTube comments were rude. My boys were 11 and 9 then. They are 17 and 15 now, and I can pretty easily see them making this same video themselves. Enjoy.

Oncologist Appointment

I had my four-month check-up with the oncologist yesterday. Things continue to look good.

As always, the appointment with Dr. R involved some blood work, a physical exam, and my own reporting of how I'm feeling.

The blood work was "perfect," as Dr. R said. It was all pretty much in line with my last few.

The physical exam was fine, too. No new nodes popping up, and nothing swollen that shouldn't be.

And my own report? Other than my physical therapist beating the crap out of me three days a week, everything seems fine.

All in all, a nice, boring visit.

The only bad part of it all was that everyone was in a sassy mood, and the whole staff messed with me. Even Dr. R stuck his head into the room while I was getting blood taken, to make fun of the Red Sox. I reminded them that they were picking on a cancer patient, but they didn't care. So mean. At least the phlebotomist, who I had not seen before, was excellent. Talk about smooth -- I didn't even know she had put the needle on. I complimented her work, which she seemed to appreciate.

One final exciting bit of news: I'll be getting a CT scan next month.

I haven't had a scan since August 2011, which was about 18 months after I had my Rituxan treatment. Things looked pretty good then, and Dr. R hasn't seen much need to get one since. But now we're coming up on three years, and he thinks it's probably time to take a look inside. I'll see him again in September, and he said there's really no rush on the scan -- any time between now and September would be fine. I'm going for it near the end of June. Most convenient, and I think I'd like to just get it over with.

It's interesting to look back and think about how much I valued scans early on. When I was first diagnosed, I thought I'd be getting them every month, and I was pretty disappointed when that wasn't the case. Now when he says "Let's hold off a while longer," I'm pretty OK with that. Time helps to ease anxiety. You get used to carrying this thing around with you. It also helps that I've been without symptoms for so long.

So I'm feeling that post-oncologist appointment sense of peace right now.

I wish you all that same peaceful, easy feeling.

Busy, Busy

I realized this morning that it has been a few days since I have posted anything to Lympho Bob. It's that time of year, I'm afraid --busy at work, the kids are all involved in time-consuming activities (and all feeling kind of stressed about it), and I haven't found anything really significant online about Follicular Lymphoma in about a week. Physical therapy for my shoulder is getting more aggressive, and taking a good chunk out of the middle of my day. I get out of there just in time to start dealing with the kids.

As I always say, though -- I'm happy to be busy, because it means I'm healthy enough to run around like a mad man.

Two quick things that I would like to point out, though:

First, it's National Nurses Week. Actually, it starts tomorrow, a Tuesday, rather than Sunday or Monday, as one might expect a "week" to start. This is because it always ends on May 12, which is Florence Nightingale's birthday. This seems appropriate, given the hours that nurses work, and the way so many of them do more than they need to. Definitely not a 9-to-5 job, and definitely deserving of our recognition and praise. I've met some doctors I haven't cared for, but dang few nurses that haven't gone out of their way to make me feel better.

Even some members of the U.S. House of Representatives thinks this is important. House Resolution 540 was introduced on April 3, "Supporting the Goals and Ideals of National Nurses Week 2014."

(Of course, it was immediately referred to the House Committee on Energy and Commerce, where it has languished without a vote, despite 21 co-sponsors from both parties. But I'm sure there's a good reason for that, and they'll get something going before May 12. (Although, voting on the resolution is not on their calendar this week. And they haven't voted on making May the official "Health and Fitness Month" or "National Allergy and Asthma Awareness Month" either, so no one should feel bad about this. They're very busy.)

(Also, as a reminder  -- midterm elections in November!)

The other thing I wanted to point out was that I see my oncologist, Dr. R, on Wednesday. I'll have an update late Wednesday or early Thursday. I'm not anticipating any problems -- I'm feeling good,at least as far as cancer stuff goes,  and I don't feel anything popping up anywhere that shouldn't be. It's been about four months since I've seen him, so we'll probably chat about my shoulder injury and horrible the Red Sox look so far this year. Maybe I'll throw in a question or two about lymphoma. I'll let you know.

And I will be sure to wish the fabulous nurses there a happy National Nurses Week. Be sure to do the same when you get a chance.

Compassion

My first follow-up visit with the shoulder surgeon came about nine days after surgery. It was much, much too early for him to be able to tell anything about how the tendon was doing. Mostly, it was a chance for him to see how surgical wounds were healing.

It was a great visit, and not just because I was still double-dosing the Oxycodone he prescribed. When he removed the dressing, it was the first chance I got to see the "entry wounds" from the surgery. It was remarkable -- three tiny holes were all that was left from the arthroscopic surgery that repaired the "mess" that used to be my rotator cuff. I'm still amazed by it.

Removing the dressing also meant I didn't have to wrap my shoulder in plastic when I showered. (Showering, with my wife's assistance, was like a Three Stooges episode. Messy, but we laughed at the end.) That was great, too.

But the best part of that visit with the surgeon was when he took off the dressing. It was taped on pretty good, and his face was just inches from mine as he peeled it all away, very slowly. I was watching him. I flinched a little, and he winced. "Sorry," he said quietly. He winced and apologized two more times before he had it all off.

That, to me, if the sign of a good doctor. He feels my pain.

It made me think of my second appointment with Dr. R -- the one where he did the Bone Marrow Biopsy. As I've said before, Bone Marrow Biopsies are about as fun they sound. I'll skip the details. I know lots of people have a hard time with them. Mine wasn't as bad as some that I've heard of -- the local anesthetic helped. But I don't remember the pain of it as much as I remember Dr. R, and how he, too, was apologetic, and careful, and compassionate. He's fairly young, and I remember thinking I was glad about that, that maybe he was still young enough to not be too cynical and jaded.

I was reminded of both of these things when I read a short piece in the Journal of Clinical Oncology by Dr. Benjamin Corn called "Acquisition of Compassion Among Physicians: Why Is This Rite Different From All Other Rites?" (If the title brings up an echo of a key line from a Passover Seder, that's deliberate, as you will see if you read the piece -- and I recommend that you do.)

Dr. Corn tells the story of how he learned compassion. It came from experiencing a doctor's lack of compassion, and, in response to this, his older brother's own act of compassion. He's writing about the importance of training doctors to be compassionate, and thinks that their own personal experiences are a good place to start, thinking about their "initial exposure to kindheartedness—or possibly, their first collision with callousness—and then begin to do the emotional work that is
required to determine how those encounters left their mark."
 
I don't know whose job it is to teach a doctor to be compassionate. Or to re-teach it. I think it's probably easy for a medical professional to get jaded, to harden her heart a little. Working in a health system to sometimes treats people as less than people will probably do that to you. And for oncologists, who deal with dire circumstances so often, I have to think that putting up some kind of wall is necessary to just get through the day sometimes.

I had the fortune and misfortune recently to see some hospice workers in action -- nurses and volunteers. It was misfortunate because it meant I had to visit someone who was in hospice care. But it was fortunate because I got to see some examples of true, amazing compassion, of being with someone to try to share their burden.

When I first read Dr. Corn's article, it made me think about the importance of compassion for our doctors. But maybe it's even more important to see it in ourselves.

Every now and then, I'll see an article or a blog post about the good things that come from having cancer. I think as I get farther along this journey, and I have more and more distance from my initial diagnosis, I'm less apt to say, "There's really no good that comes from having cancer," and more apt to look for the good things.

And maybe one of those good things is that we as cancer patients can see others hurting, and understand where they are just a little more. Not just physical hurting, because that's only part of being a cancer patient. But emotional and mental and spiritual healing, too.

In a world that seems increasingly less compassionate, and more interested in looking at a screen than looking into someone else's eyes, maybe our own compassion can be an example for others.

Bendamustine for Follicular Lymphoma

This month's Medical Oncology journal offers a review article on Bendamustine (aka Treanda) as a possible first-line treatment for Non-Hodgkin's Lymphoma. To be clear: it isn't offering any new research about Bendamustine. Instead, it discusses some of the recent research to argue that it might be time to consider Bendamustine as first choice.

Right now, in the U.S., the FDA has approved Bendamustine as a second-line treatment for indolent lynphomas (including Follicular Lymphoma), used within six months of treatment with Rituxan (or a combination involving Rituxan) if the disease has progressed. It gets used in ways other than that, but the authors of this article think we should make that official.

(If the link above doesn't take you to the article, try this one, the journal's home page, and scroll down to the link "Bendamustine-based therapy as first-line treatment for non-Hodgkin lymphoma.")

 The article looks at studies of Bendamustine as it is used for patients with indolent lymphomas (including Follicular Lymphoma), Mantle Cell Lymphoma, and aggressive lymphomas (including DLBCL). The indolent lymphomas are the ones that matter most to me (and probably you, if you're reading this).

The section on indolent lymphomas looks at a bunch of published studies, as well as some recent conference presentations. The biggies are there, including studies that compared Bendamustine and Rituxan with CHOP, and again with CHOP and CVP. Bendamustine, of course, came out on top of these studies, with greater effectiveness and, just as importantly, less toxicity.

The low toxicity (and few side effects) of Bendamustine are big part of the authors' argument. The reasons for its low toxicity are still not fully understood, and the authors recommend more long-term study of side effects, but for the most part, Bendamustine is safer than other options. It is more cost-effective than COP or CVP, in part because there is less need to deal with side effects.

So, again, this article doesn't present anything new. But it does suggest that it's time to consider Bendamustine as an approved first-line treatment. It's certainly used that way now, but it would be nice to make it all official.

Predicting a Follicular Lymphoma Diagnosis

Fascinating research from France published in the Journal of Clinical Oncology: a genetic test might predict a Follicular Lymphoma diagnosis long before the disease shows up. (Not that any such test exists at the moment. Read on.)

Researchers from France (and I mean pretty much every lymphoma researcher in France, from the looks of the list of authors) tapped into the 520,000 people participating in a European study of cancer and nutrition and found 100 people with Follicular Lymphoma. Going back to earlier blood samples from this group, they found that there was a link between Follicular Lymphoma and a translocation of the (14;18) chromosomes.

This particular bit of information isn't new; we've known for a while that (14;18) translocation is present in Follicular Lymphoma cells. I'm not going to get too much into genetic stuff, but basically what happens is this: chromosomes play a key role in cell division and replication. They make sure that DNA (the blueprint for cells) divides properly when a cell divides. Humans have 23 pairs of chromosomes, so it's easy to number them. "Translocation" means the chromosomes have changed their location. As you can imagine, when something that supposed to help organize a cell splitting gets mixed up itself, there are problems. It's kind of like putting a drunk guy in charge of a bakery -- you're going to get some messed up cupcakes.

And that's what cancer is, really -- a bunch of messed up cupcakes.

Anyway, for Follicular Lymphoma, there is a translocation of the number 14 and number 18 chromosomes. Drunky McBaker added a half cup of salt when he should have added a half cup of sugar. Your salted caramel cupcakes end up way too sweet, and your red velvet cupcakes end up way too salty. And the baker is passed out behind the stand up mixer, so he's no help.

Back to Follicular Lymphoma: when the (14;18) translocation happens, the normal signals to the cells get mixed up, and we end up with problems. In this case, the problem is a bad one: a cell that has lost the ability to die. And that's what cancer is, in a nutshell. (Or a cupcake wrapper.)

What is significant about what this group of researchers from France have discovered is that the (14;18) translocation can be detected long before there is an official diagnosis of Follicular Lymphoma: up to 15 years before diagnosis.

That's pretty amazing.

Now, the real question is, what are the implications of this?

For us, as current patients, probably not much, at least directly. Knowing that I might have had a better shot at getting lymphoma 15 years ago doesn't do much for me now.

Will it help others in the future? Maybe. But I'm not sure, at this point, that it will. It would mostly give them something else to worry about for 15 years.

The really helpful thing it might do, though, is help researchers track changes over time that lead from the translocation to the need for a diagnosis. Maybe they can track changes in the microenvironment that cause the translocation to develop into full-blown FL. Understanding the disease's path will provide information on ways to impede that path before it gets out of hand.

In some ways, the indolent nature of Follicular Lymphoma may be a blessing, if its slow growth allows us to see a clearer picture of what's happening.

I think this is one of those research reports that is a bigger deal than it seems at the moment. It's not a "Hey, we added 2 years to Overall Survival!" report. But it's one that adds just a small piece to the big puzzle, and it might turn out later to be a very key piece.