Tuesday, May 13, 2014

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?

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