Friday, May 14, 2010

Provenge, And Mylovenge

Several weeks ago, the FDA approved for certain types of refractory (i.e. unresponsive to standard treatment) cases of prostate cancer a new "vaccine", brand name Provenge. The reason I'm using the scare quotes here is that Provenge is not a vaccine in the conventional sense; no one who does not already have prostate cancer will be taking Provenge to avoid getting it. The mass media is using the term "vaccine" to characterize Provenge because it's a term that is much more familiar to the general public (not to mention more concise) than is "autologous cellular immunotherapy", and because it serves to convey an important fact about the drug: like an ordinary vaccine, it enables the patient's immune system to combat the cancer. A patient's white blood cells are extracted, are treated with the drug, and are then returned to the patient, having now been "taught" to recognize the cancer cells as things that should be attacked and destroyed. Provenge is the first therapy of this type approved by the FDA for the treatment of any type of cancer.

Therapeutically speaking, Provenge isn't notably impressive. It extends survival by only four or five months, and it doesn't seem to affect tumor progression at all, which is apparently one of the reasons why the FDA had such trouble granting approval for it, finally doing so about ten years after it was first presented. And it will of course be appallingly expensive, thus giving rise to yet another of those "health care rationing" conundrums that we seem to specialize in creating.

But in conceptual terms, one can visualize Provenge as being the prototype for an extremely effective class of future cancer therapies. The immune system's job is to attack and destroy bad guys; cancer cells are bad guys that diabolically pretend not to be; the obvious answer is to somehow make the immune system see through the cancer cells' disguises for what they are, and go git em. That's what Provenge, and its presumed successors, would seek to accomplish.

So what does this have to do with multiple myeloma? Nothing, except that at one time
-- ten years ago -- Dendreon, the company that developed Provenge, was working on a vaccine for multiple myeloma, called Mylovenge. Mylovenge was at some pointed granted "orphan drug" status by the FDA (thus qualifying it for certain types of research-related tax credits), and it reached Phase II clinical trials by 2002 or thereabouts. And then.... nothing. I was able to find traces of a clinical trial involving Mylovenge that completed in 2005, but not the results of the trial. There is nothing mentioning Mylovenge on Dendreon's web site, and calls to Dendreon's corporate offices proved fruitless. Intense Googling turned up a claim that Dendreon stopped working on Mylovenge when it became apparent that it would be difficult to manufacture, and that its therapeutic results compared poorly with those of other types of drugs that became available in the meantime -- drugs that didn't require the expensive and cumbersome pheresis process.

In fact, Mylovenge is the tip of a large iceberg of relative failure for cancer immunotherapies. This idea -- that the battle should be fought by the immune system -- as reasonable as it sounds, has proved difficult to implement in practice. Many types of immunotherapies have been developed and tested during the past couple of decades, to little practical effect so far. No doubt a tremendous amount has been learned in the process, but to date this knowledge has not been translated into longer lives for cancer patients. Reading the press around the Provenge approval is attended by deja vu: the potential of the immunotherapeutic approach is set forth in terms almost identical with researchers' promises made ten or fifteen years ago. That's not the researchers' fault, really; this stuff is hard, harder probably than anyone would have guessed at the beginning.

And now, suddenly, the President's Cancer Panel comes out of left field with a report declaring that the environmental causes of cancer have been "grossly underestimated", and recommending that maybe someone should look into this. So at this point, the larger problem of cancer -- where it comes from, and how to stop it -- is still generating many more questions than answers.

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