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.

This Month's Tests

The monthly routine into which my medical life has settled goes something like this: A few days prior to visiting the oncologist, I have blood drawn for the battery of tests he wants to do. The office visit itself of course begins in the outermost waiting room; eventually I am called upon by a physician's assistant, who weighs me before ushering me into an examination room, where I await my audience with His Lordship. Upon entering, he gives me a glance up and down and pronounces his satisfaction with my appearance; then he jumps onto a computer, brings up my test results, mutters a bit about one number or another, but finally declares his general approval of the aggregate. He inquires about any pain I might be having, but am not. Then I'm up on the table while he listens to my lungs and heart, and gently probes my belly and squeezes my ankles. We talk about whether he needs to write any prescriptions for me. Finally, it's Q and A time, which these days usually is brief, although this month we chatted a bit about the new vaccine recently approved for prostate cancer, and whether there is anything like that being developed for multiple myeloma (but that's a subject that deserves a post of its own). Finally, on the way out, I schedule my next office visit, and a session for an Aredia IV, which ordinarily occurs a day or two later.

The blood tests that are being done fall into one of three broad categories, from my perspective. One category is that of blood cell counts: red, the various types of whites, and platelets. This month, these were all within their normal ranges, except that I am a bit low on red blood cells. This is a side effect of the Revlimid, and is a factor in my fatigue problem.

A second category of tests I think of as "levels of chemicals in the blood", stuff like calcium, sodium, potassium, creatinine, and glucose. Currently these are all in their normal ranges.

The third category is that of proteins and immunoglobulins (a.k.a. antibodies). Oversimplifying greatly, we want to see adequate numbers of the types of antibodies expected to be produced by normal plasma cells, and we don't want to see any of the junk monoclonal proteins produced by defective, cancerous plasma cells. Again, currently the tests are showing more or less the right numbers of the former, and none of the latter. I will continue to take Revlimid as long as this state of affairs continues.

Meanwhile, the monthly Aredia treatments are supposed to be strengthening my bones; this, in concert with suppression of the disease that caused them, should be making some of the lytic lesions on my spine disappear. I haven't had a skeletal survey for awhile, so I will get one sometime in the next month or so, thus giving us a reading on how well I'm doing on this front.

Revlimid In The UK

I have been wondering how I would be faring in one of the socialist paradises possessing a single-payer health care system, such as the UK. Answer: It's not clear, to me.

Here I'm considering solely the position Revlimid occupies in the National Health Service's scheme of things. The determination about whether or not the NHS will pay for a particular therapy in particular circumstances for a particular class of patients is made by the National Institute for Health and Clinical Excellence (NICE). This is what certain former governors of Alaska are referring to when they talk about "death panels": inevitably, NICE will decide that a very expensive cancer drug that, statistically, extends the life of patients by only a few months is not "cost-effective", and that the NHS should not pay for said drug. Thus, some small minority of patients who would in fact have had their lives extended by many years had they gotten this drug will not get it, and will die very prematurely. Of course, on the other side of the coin, we have the problem of limited NHS resources: any money spent on said drug, mostly to very limited effect, cannot be spent on other things; if spent on these other things, conceivably many more people could have their lives extended or improved. This is what the term "cost-effective" is supposed to mean in the first place; but you see the problem, which is that the NHS must explicitly ration health care resources, and politically (morally?) it must do so on some basis that appears to be at least vaguely objective, which it calls "cost-effectiveness".

I was surprised to learn that the NHS does not negotiate drug prices; isn't this supposed to be one of the major advantages of single-payer systems? Instead, NICE must be approached by the provider of a proposed therapy with a pricing model under which the provider would be compensated by the NHS; NICE then makes a binary yes/no decision on the cost-effectiveness of the therapy, based on the proposed pricing model, and on whatever scientific evidence is available regarding the therapeutic efficacy of the therapy.

Until early 2009, NICE apparently was opposed to approving Revlimid for any purpose whatsoever. Then Celgene, the maker of Revlimid, offered a deal: if the NHS paid for the first two years of a patient's Revlimid treatments, Celgene would pick up the tab itself after that, for as long as the patient lasted. Based on this proposal, NICE reversed itself to some degree, approving Revlimid for multiple myeloma patients who had received two prior therapies. In other words, my usage of Revlimid as front-line therapy would not have been paid for by the NHS. Perhaps my current usage as maintenance therapy would pass muster, depending on exactly what is meant by "two prior therapies"; would induction therapy count as one therapy, and the stem cell transplant as a second? I'm not certain. I'm also not certain whether NICE considered Revlimid for front-line therapy and turned it down for that, or whether this usage was not even on the table.

And this reminds me of an anomaly in my own case: technically, Revlimid is not approved as a front-line therapy by the FDA either; yet I got it for such, and the medical insurance company was just fine with that. The US rations health care resources as well, but no one is allowed to admit that this is both necessary and inevitable, and should be properly called by that name; it is currently carried out based on the seemingly arbitrary policies of whatever medical insurance provider one happens to have, or on the fact that one has none. News flash: We already have "death panels" de facto. But no one calls them NICE.

The "Chemo Parity" Issue

This Washington Post article discusses the "chemo parity" problem, which was not addressed by the recently-passed national health care legislation. The new oral chemotherapy drugs are very nice, but they also tend to be very expensive, and often are covered inadequately by drug plans, thus forcing patients back onto IV chemotherapy drugs, which are usually covered by medical plans, rather than by drug plans. And of course things get much uglier in those cases in which no IV drug is available, or the patient's disease has become IV drug-resistant.

There is a paragraph in here that talks about multiple myeloma patients who take Revlimid, which is described as being required "after an IV drug stops working". I took Revlimid last year as stem cell transplant induction therapy, and I'm taking it now as maintenance therapy; I have never been given an IV drug that "stopped working". Either the Post or its source for this part of this story is behind the curve on how Revlimid is currently being used in multiple myeloma cases.

A Reluctant Teetotaler

As I believe I mentioned as far back as the very first post of this blog, I possess a cellarful of wine, with which I now maintain a troubled relationship. Of course, when I first became ill, the bottles nestled comfortably unmolested in their bunker for months on end. By Thanksgiving, I was able to have a glass or three with dinner, but almost immediately thereafter the stem cell transplant campaign began, and I once again had to forego the pleasures of the grape. But when I returned to Johns Hopkins in February for my 60-day follow-up, the oncologist gave me permission to take them up again, in moderation. So after a decent interval, I tried to resume, but the experiments have not gone very well. Something about alcoholic beverages upsets my stomach and causes me to feel nauseous. I have tried to gauge the minimum amount that causes these effects, but I am unable to get reliable results. So I am calling a halt to the trials for now.

I am assuming that this is caused by some interaction with one or more of my current roster of medications. For now, I am going to guess that I need more time to re-acclimate myself to the Revlimid, so I will try again in another month or so. If it turns out to be down to one of the antibiotic or anti-viral drugs then I have longer to wait. If it turns out that something has permanently changed, and I am no longer physically capable of tolerating the stuff, then you can just shoot me.

I'm Tired of Feeling Tired

My low-dose maintenance chemotherapy began on March 24. Two weeks into the first cycle, I'm getting used to Revlimid again, after not having taken any since sometime in November. The side effects are mild: a little tingling in the fingertips; some constipation and general gut disturbance; a bit of rash on the face. Thankfully, there are no muscle spasms, probably because dexamethasone is not part of the equation this time.

Now that the immediate existential threat has retreated (although it continues to lurk like a black cloud just over the horizon), I am reduced to focusing on what seems, by contrast, almost trivial. For example: The most frustrating aspect of my current situation is the unpredictable duration and intensity of fatigue and weakness. Some days I wake up, having slept comfortably through the night, and after performing my morning ablutions and having breakfast, feel the urge to return to bed. But if actively resisted, the feeling often simply dissipates. I can now walk two miles (cane-assisted) without stopping to rest en route, and often without even feeling the need to rest afterwards. In fact I often feel better at that point than when I began. I still crash for naps at odd times of the day, but not as often as before. On the other hand, anything involving lifting and carrying any weight, or just crouching to reach something low, seems to take an inordinate amount of energy. It's not as bad as it used to be, but it still seems to be the single most prominent factor standing between me and a feeling of normalcy (or as close to normalcy as I'm likely to get). I'm considering returning to physical therapy to work this problem.

The Feds Think I'm Disabled

This past week I received from the Social Security Administration notification that it had come to the conclusion that I am indeed disabled, and have been so since June 2009. This will result in monthly payments from the SSA, but the monthly private LTD insurance payments that I have been receiving since October will be reduced by a corresponding amount, so financially speaking, this event is a wash.

The other benefits are somewhat longer-term in nature. The first is that I will become eligible for Medicare coverage in November 2011. That would be several months beyond when my current COBRA coverage would end. But I may be eligible for an extension of that coverage; I must have a little dance around that issue with the company administering the COBRA plan. Of course I hope to return to work before any of these dates matter, but I must make sure that the issue is resolved in advance, in case my hopes do not come to fruition for some reason.

Second, the SSA provides for a "trial work period", lasting nine months, during which my disability status would remain unchanged, and the associated payments would continue as usual, even while I was working. If, before the end of the trial period, I found that I was unable to sustain the effort to work normally, then I would remain with the original disability status. The astonishingly good idea is to allow the disabled person to determine whether or not he is truly capable of leading a normal work life again by actually doing so, without having to completely disavow his disabled status all at once. I'm not sure how the private LTD insurance would work in such a scenario; that is something I will have to research.

Third, if the disabled person continues to work beyond the end of the trial work period, but then is eventually (within five years) forced by his condition to again stop working, he can request "expedited reinstatement", which if granted would cause payments to resume immediately, without having to begin with a new application all over again. This seems tailor-made to fit precisely the circumstances of the typical cancer patient who has achieved a precarious, possibly impermanent remission, whose disease could rise up again at any moment, forcing the patient back into a debilitating regime of rough treatment at the hands of the oncologists. Again it isn't clear how the private LTD insurance would work in this instance.