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.
Sunday, April 28, 2013
Tuesday, March 26, 2013
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.
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.
Tuesday, March 5, 2013
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.
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.
Monday, February 25, 2013
The Myeloma Blood Tests
This month's myeloma blood test results moved slightly off center. Since I don't recall previously discussing all of these tests, now would probably be a good time to do that.
I do remember mentioning the free light chain tests a year or so ago, the last time they attracted this kind of attention. This time the kappa free light chain number is a shade over the top of its normal range, while the lambda and kappa-lambda ratio numbers are normal. These tests are simply measuring the concentrations in the blood of these molecules, in milligrams per liter.
The other two tests seem more subjective in nature. They involve an examination by a trained analyst of "pictures" representing the behavior of blood proteins that have been subjected to certain processes.
In serum protein electrophoresis (SPEP), blood proteins are placed at one end of a agarose gel to which an electrical current is applied. Different proteins migrate to different locations in the electrical field on the gel; if monoclonal proteins are present in significant quantities, they will show up as a dense, narrow discrete band in the gel. Of course, depending on the patient's situation, this band may be more or less dense, and more or less narrow; this is not a binary, yes/no the patient does/doesn't have myeloma test. In my case, the analyst's comment says: "A very faint discrete band."
The immunofixation electropheresis (IFE) test attempts to further validate the presence of monoclonal proteins by identifying the heavy and free light chain components involved. The electrophoresis is repeated in five "lanes" on the gel; to each lane an antibody specific to one of the three heavy chains or two light chains is applied. An antibody reaction will cause a telltale precipitation band to be left behind in that lane. A band in a heavy chain lane, paired with a band in a light chain lane, identifies a specific type of monoclonal protein. In my case, the analyst's comment says: "A very diffuse IgG Kappa band seen."
Obviously, experienced hematologists could express differences of opinion regarding the significance of such phrases as "very faint" and "very diffuse", when used in this context. For his part, my oncologist, a phlegmatic, conservative sort, seems at least outwardly to be unimpressed by all of this. We will run these tests again next month, he says, and we will see.
I do remember mentioning the free light chain tests a year or so ago, the last time they attracted this kind of attention. This time the kappa free light chain number is a shade over the top of its normal range, while the lambda and kappa-lambda ratio numbers are normal. These tests are simply measuring the concentrations in the blood of these molecules, in milligrams per liter.
The other two tests seem more subjective in nature. They involve an examination by a trained analyst of "pictures" representing the behavior of blood proteins that have been subjected to certain processes.
In serum protein electrophoresis (SPEP), blood proteins are placed at one end of a agarose gel to which an electrical current is applied. Different proteins migrate to different locations in the electrical field on the gel; if monoclonal proteins are present in significant quantities, they will show up as a dense, narrow discrete band in the gel. Of course, depending on the patient's situation, this band may be more or less dense, and more or less narrow; this is not a binary, yes/no the patient does/doesn't have myeloma test. In my case, the analyst's comment says: "A very faint discrete band."
The immunofixation electropheresis (IFE) test attempts to further validate the presence of monoclonal proteins by identifying the heavy and free light chain components involved. The electrophoresis is repeated in five "lanes" on the gel; to each lane an antibody specific to one of the three heavy chains or two light chains is applied. An antibody reaction will cause a telltale precipitation band to be left behind in that lane. A band in a heavy chain lane, paired with a band in a light chain lane, identifies a specific type of monoclonal protein. In my case, the analyst's comment says: "A very diffuse IgG Kappa band seen."
Obviously, experienced hematologists could express differences of opinion regarding the significance of such phrases as "very faint" and "very diffuse", when used in this context. For his part, my oncologist, a phlegmatic, conservative sort, seems at least outwardly to be unimpressed by all of this. We will run these tests again next month, he says, and we will see.
Saturday, February 16, 2013
The Revlimid Paper Chase
No doubt you are used to getting a bit of paper whenever you go to the local pharmacy to pick up a prescription. Nowadays typically there is included with even the most seemingly innocuous of nostrums a "Medication Guide", printed on fan-folded tissue paper, that describes, unreadably and at considerable length, how to take the stuff; how not to take the stuff; all the bad things that could happen, maybe, if you dare to take the stuff; what to do and whom to call if any of these bad things happen; and so on.
But you never, ever read any of this mind-numbing material. Am I right?
News flash: This stuff isn't for you, the patient; it's for every one else involved in the process of delivering the products of the pharmaceutical-industrial complex. It's a liability-limitation mechanism. If something bad happens to you as a result of swallowing a few billion milligrams of Skeezix 100mg tabs, and an ambulance-chaser persuades you to sue the manufacturer, the defense's attorney will want to know whether the plaintiff actually read all this stuff, as required, and fully understood the risks involved. No? Well then: Your honor, this is clearly a deplorable example of the irresponsible misuse of a product the safety of which, when used as directed, has repeatedly been demonstrated blah blah blah.
Every 28 days the UPS man brings a little box to my door. It contains a plastic bottle containing 28 pills, and a quantity of paper. Some of the paper is packing material. But there is also the usual Medication Guide... and 16 standard 8-1/2x11 pages of additional stuff, mostly identical every time, and mostly recycled without much ceremony by yours truly:
An invoice (one page), in the quantity of my minuscule co-pay. The true invoice, for something like $10000, is not included; that is sent to the medical insurance company. I can see it only if I log into my account on the medical insurance web site.
"Important Drug Information" (4 pages). In effect a reprise of the material of the standard Medication Guide, but organized in a different manner, and "personalized" with my name, my oncologist's name, my pharmacy account number, etc.
"Medication Guide" (3 pages). Yet another copy, in a different format, of exactly the same material as the Medication Guide mentioned above.
"General Information about Cancer" (7 pages). Answers such burning questions as "Are there cancer treatment side effects?" (Ummm... Yeah.); and "Do I need to finish my chemotherapy even if I feel better?" (Nah, that's for sissies, pilgrim. But the last page warns against doing anything without asking your doctor first. So we're covered, counselor.)
And finally, a whole page of "Helpful Information Regarding Your Prescription", including such gold as "How do I convert the convertible cap to a non-safety cap for easy opening?".
What a comfort it is, to know this is possible.
But you never, ever read any of this mind-numbing material. Am I right?
News flash: This stuff isn't for you, the patient; it's for every one else involved in the process of delivering the products of the pharmaceutical-industrial complex. It's a liability-limitation mechanism. If something bad happens to you as a result of swallowing a few billion milligrams of Skeezix 100mg tabs, and an ambulance-chaser persuades you to sue the manufacturer, the defense's attorney will want to know whether the plaintiff actually read all this stuff, as required, and fully understood the risks involved. No? Well then: Your honor, this is clearly a deplorable example of the irresponsible misuse of a product the safety of which, when used as directed, has repeatedly been demonstrated blah blah blah.
Every 28 days the UPS man brings a little box to my door. It contains a plastic bottle containing 28 pills, and a quantity of paper. Some of the paper is packing material. But there is also the usual Medication Guide... and 16 standard 8-1/2x11 pages of additional stuff, mostly identical every time, and mostly recycled without much ceremony by yours truly:
An invoice (one page), in the quantity of my minuscule co-pay. The true invoice, for something like $10000, is not included; that is sent to the medical insurance company. I can see it only if I log into my account on the medical insurance web site.
"Important Drug Information" (4 pages). In effect a reprise of the material of the standard Medication Guide, but organized in a different manner, and "personalized" with my name, my oncologist's name, my pharmacy account number, etc.
"Medication Guide" (3 pages). Yet another copy, in a different format, of exactly the same material as the Medication Guide mentioned above.
"General Information about Cancer" (7 pages). Answers such burning questions as "Are there cancer treatment side effects?" (Ummm... Yeah.); and "Do I need to finish my chemotherapy even if I feel better?" (Nah, that's for sissies, pilgrim. But the last page warns against doing anything without asking your doctor first. So we're covered, counselor.)
And finally, a whole page of "Helpful Information Regarding Your Prescription", including such gold as "How do I convert the convertible cap to a non-safety cap for easy opening?".
What a comfort it is, to know this is possible.
Sunday, February 10, 2013
Pomalidomide
The multiple myeloma treatment arms race has really been heating up. Practically on the heels of FDA approval of Onyx's carfilzomib (branded as Kyprolis) comes approval for Celgene's latest thalidomide derivative, pomalidomide (branded as Pomalyst). Once again this entry is fenced about by theoretical restrictions (only for patients who have failed at least two other treatments, please) that will yield in practice to further research. Unsurprisingly given its lineage, pomalidomide seems to do better with a low-dose dexamethasone amplifier. Also unsurprisingly, these new agents are doing nothing to reduce the cost of treatment; both will run more or less the same $10000/month as my old reliable Revlimid.
Monday, September 3, 2012
Thalidomide
This Washington Post (actually rehashed AP wire service) article revisits the thalidomide disaster, in the context of the controversy over the original German manufacturer's recent "apology" to the victims, fifty years after the actual events. The article stands on its own merits; but at the very end, it mentions that thalidomide is currently used to treat multiple myeloma, which it identifies as a "bone marrow cancer". Gah.
Subscribe to:
Posts (Atom)