Official: Return to Treatment

This past Friday, Huong and I met my new oncologist for the first time. A woman of Indian heritage considerably younger than myself, she took immediate control of my case, and established that she would be substantially more aggressive than the old guy (whom she claimed as her mentor) had been. Once again the blood test numbers have crept up slightly, and she wants to head off the disease by, for now, restoring the 25 mg dosage of Revlimid. The reader may recall that this was my original dosage on returning from Johns Hopkins 3-1/2 years ago, but it was reduced to 10 mg in view of the second cancer development risk associated with long-term exposure to Revlimid. But now fear of the resurgence of the actual first cancer has overtaken the speculative fear of a second one. She is also shifting me to a full 325 mg aspirin daily, up from 81 mg, against the increased risk of blood clots arising from the higher Revlimid dosage.

For next time, she has requested that I undergo another UPEP (urine protein electrophoresis) test, to get a set of fresh baseline results for that.

Meanwhile, none of this is having much impact on my daily life. I continue to work and play as normal. I have just returned more or less intact from an arduous three-week trip overseas. My disease-related "issues" (back pain, fatigue, gastrointestinal instability) exhibit neither deterioration nor improvement in the recent past. The changes are, so far, completely test-driven.

No Symptoms, Yet

The question has arisen: Given the apparent progression, am I noticing any new or different symptoms? The short answer is "No". Other than the fact that my digestive tract seems more stable, if it weren't for the advancing test numbers, I would have no inkling that anything has changed. To use medical establishment terminology: "No clinical evidence."

Major Transition

The blood test numbers continue to edge up -- monoclonal proteins are now 0.4 g/dL, vs. 0.3 last month; and kappa free light chains are 23.1 mg/L, up from 21.3. Lamba free light chains also increased, though, so the ratio actually declined to 1.24, from 1.46. Nevertheless, this "progression" -- the oncologist allowed himself to utter the word this time -- is "real", not some noise in the testing process.

We agreed that, since in a couple of weeks I will be leaving the country for several weeks, now would be a bad time to make any changes to the medication regime. Given the seemingly glacial rate of progression, the risk that the disease will suddenly get out of control in that time is comparatively lower than the risks potentially arising from a change in medication. Also, there remains the psychological barrier: "Once you go from 'maintenance' to 'treatment', there is no turning back."

And having said that, with one engine on fire and the other one losing oil pressure, the oncologist strapped on his parachute and lept out of the open hatch. Shortly after my last visit with him, I received a letter from his group announcing his retirement, effective August 1. So my next appointment will be with a physician I have never met.

May: Additional Tests

For May, the oncologist added to the usual blood tests the more accurate 24-hour urine protein electrophoresis (UPEP), and an x-ray bone survey. The blood tests spoke of stability, more or less, with monoclonal proteins remaining at 0.3 g/DL, and kappa free light chains edging up to 21.3 mg/L, but the kappa/lambda ratio remaining in the normal range at 1.46.

Interestingly, the UPEP test showed no monoclonal proteins at all; but "polyclonal free light chains and polyclonal IgG seen". Taken together, nothing the oncologist takes as meriting any kind of alarm.

The final impression on the bone survey was equally bland: "Stable metastatic bone survey compared with 12/29/2011." There was not even any additional compression of T8 noted, which is one of the things I was fearing. The worst that could be said was: "Stable lumbar spine with degenerative changes in the lower levels", which probably could be said of any male in his late 50's.

On the whole, there is just nothing to get excited about at this time.

April Tests: Inconclusive

For some reason, April's test results were slow to arrive at the oncologist's office this past week (first time this has ever happened). We have them now, but are perhaps not much the wiser for it. Kappa free light chains backed off slightly, and are now barely above the top of the normal range; the kappa/lambda ratio is well within its normal range. On the other hand, the monoclonal spike in the gamma region edged up to 0.3 g/dL.

The oncologist continues to keep his powder dry. He still does not want to change anything -- yet. But he mentioned for the first time the possibility of "changing the dosage". That would mean boosting to 15 mg or 25 mg Revlimid, from the current 10 mg. Attentive readers may recall that on my return from Johns Hopkins 3 years ago I was started on 25 mg, which was subsequently reduced to 10 mg in view of the increased second cancer risk associated with long-term Revlimid exposure. But we may have to assume that risk once again.

Beware The Tests of March

The myeloma blood tests are "headed in the wrong direction", to use the expression of the nurse practitioner who reviewed this month's results with me. The free light chain numbers are virtually unchanged. But the SPEP comment reads: "Monoclonal spike seen in the gamma region = 0.2 g/dL." For IFE we have: "Monoclonal IgG Kappa seen."

Few phrases are as calculated to stoke the long-term myeloma patient's anxiety as "monoclonal spike". An ocean of bad memories lap at the veteran's feet. The notion that the cancer cells themselves seem to be multiplying is bad enough; but then one visualizes the garbage that they pump out, clogging the delicate filters of the kidneys, freezing the struggling musculature of the heart, crushing the shielding of the nerves as if in a slowly tightening vice. The tormented osteoclasts resume their mindlessly feverish drilling of the bones. The patient's mind and spirit are once again imprisoned in a body that is its own worst enemy.

In these circumstances, the oncologist's rationalizations are comforting: 0.2 g/dL is still minuscule; two data points don't make a curve; and so on. Only in case next month shows significant further deterioration must we consider taking evasive action. Wait until next month.

Generics, Authorized and Otherwise

Last summer's discussion of generic Revlimid attracted an unusual amount of attention, so I thought I would expand a bit on the regulatory environment for generics. 

In the United States, competition law is administered and enforced by two distinct government entities: The Federal Trade Commission and the Department of Justice Antitrust Division. The relationship between them is complicated, and I am greatly oversimplifying here, but in general the FTC pursues the enforcement of antitrust and consumer protection laws in civil courts, while the Antitrust Division has the power to bring criminal charges in cases of violations of antitrust laws. In recent years, maneuvers undertaken by patent-holding pharmaceutical companies and their generic-making competitors have attracted the attention of the FTC, and prompted legal actions by it.

Consider the hypothetical case of MegaFarma Inc., the holder of patents on, and exclusive manufacturing and marketing rights to, a very expensive therapeutic agent, wigglidomide (brand name Skeezix). Skeezix is coming off patent soon, and a maker of generics, LoPillCo, is known to be working on a much less expensive, bio-equivalent version of wigglidomide, to be pushed onto the market the moment that happens. There are a couple of things that MegaFarma thinks it might do to delay this event.

In a "pay-for-delay" agreement, MegaFarma would simply bribe LoPillCo to delay the introduction of its generic wigglidomide for some period of time. During that time, MegaFarma's domination of this particular market would remain unimpaired, LoPillCo would get substantial sums of cash for doing literally nothing, and everyone is happy. Everyone, that is, except the consumers (and notably the much-maligned medical insurers), who would continue to pay the usual elevated prices for Skeezix. And the FTC. The FTC is not at all happy with pay-for-delay, and in at least one case has chased the appeals process in a case against such an agreement all the way to the Supreme Court.

A somewhat subtler move for MegaFarma would be to introduce, or rather threaten to introduce, its own "authorized generic" wigglidomide, i.e. a repackaging of Skeezix itself as a generic, when it goes off-patent. Doing this could be assumed to be deleterious to LoPillCo's business model around wigglidomide. In fact MegaFarma has no desire to win a race to the bottom of the market for generic wigglidomide; what it really wants is a "No-AG" agreement with LoPillCo, in which LoPillCo would delay the introduction of its generic for some period of time, at the end of which MegaFarma would not counter with its own generic, thus leaving to LoPillCo unmolested (at least by MegaFarma) control of the market for generic wigglidomide. The FTC is unhappy with No-AG agreements as well, for pretty much the same reasons, and has undertaken similar actions against them.

These agreements are not an occasional problem. By law, agreements between brand and generic companies resolving patent disputes must be filed with the FTC; of 140 such agreements filed during the fiscal year ending 30 September 2012, the FTC believes that 40 of them involve some form of pay-for-delay or no-AG. It estimates that these agreements cost consumers an estimated $3.5 billion annually.

Finally, MegaFarma may choose to try to evade the generic competition altogether, rather than reach some sort of rapprochement with it. Thus, the phenomenon of "product hopping", a term applied to a process involving the dropping of a branded product altogether, and its reintroduction into the market in some slightly altered form -- rarely if ever a therapeutically improved form, incidentally -- thus moving the target for LoPillCo rather late in the game. News flash: The FTC doesn't care for this gambit, either, and has said so in court.