Sunday, January 5, 2014

2014: Better Times Ahead, I Hope

I may return later to provide an account of the ordeals of the past two months, but rather than get bogged down in all those messy details at this point, I will simply set out the current situation.

I am tethered 24x7 to a portable IV pump that is dosing me with the antibiotic oxacillin every four hours. This will continue through the month of January, at the end of which time blood cultures will presumably reveal no trace of the staph infection that caused so much havoc. I have a daily ritual in which I replace the empty IV bag with a fresh one. Once a week a nurse arrives at the house to replace the dressing around the PICC line in my left arm (installed during my hospital stay) to which the pump is attached, and to take blood for any tests ordered by the infectious disease doc running this show. The major side effect I am struggling with here is the fact that the oxacillin is killing the good bacteria in the gut that is required for proper digestion, alongside the bad bacteria. I am trying to counteract this effect with probiotics supplements. My appetite varies from poor to fair; I am supplementing occasionally with bottles of Ensure.

I am two weeks into what is at least for starters a four-week program of physical therapy designed to get the left knee that was sliced open in pursuit of the staph infection going again. So far the therapist in charge of my case is happy with progress in this area.

Chemotherapy was finally reinitiated on December 19. The protocol is not what I was thinking it would be a couple of months ago. It involves the novel agent carfilzomib (brand name Kyprolis) and the steroid dexamethasone, both administered via IV. I get these on days 1, 2, 8, 9, 15 and 16 of each 28-day cycle. So far I can discern no meaningful side effects, other than maybe some temporary temperature boosts caused by the dex; this effect is nonetheless bothersome, since given the staph infection situation I must constantly be on the lookout for fevers.

In the pain management area, I am sticking solely to acetaminophen, and that only occasionally, for example if the left knee is preventing me from sleeping. I emerged from the hospital popping oxycodone on top of twice-daily slow-release oxycontin; I have weaned myself from both and am religiously avoiding any and all opioids, since they have the effect on me of constant daytime drowsiness, which renders me nearly useless, in terms of doing things. I was falling unconscious in my chair at any moment.

I am currently not working; all the time taken up by various medical appointments during the week make that impossible. Once the issues unrelated to chemotherapy are resolved, presumably by the end of January, a return to work should become much more plausible.

Friday, November 1, 2013

The New Treatment Plan: CyBorD --> CyCarD

It sounds like the name of some dangerous computer malware, or perhaps the latest secret NSA surveillance program. Instead, "CyBorD" is the name of the protocol that I will soon [not, as of 10/30/13] begin following as treatment against the advancing multiple myeloma. CyBorD indicates a combination of cyclophosphamide, bortezomib, and dexamethasone. It's also called VCD, using the names of the branded agents involved (Velcade, Cytoxan, and dex).

This proposal of the Christiana oncologist came as something of a surprise to me. None of these is, strictly speaking, a particularly novel agent. Velcade (bortezomib) is a member of the first generation of such agents that included for example Revlimid. It has been used successfully for a decade, very often as a part some sort of combination such as this. [10/30/13: Kyprolis/carfilzomib, the next-generation successor to Velcade/bortezomib, will be substituted for it.]

Cytoxan (cyclophosphamide) is really old-school; clinical trials involving it were first conducted in the late 1950's. It's the traditional type of agent that many people continue to associate with the term "chemotherapy"; it makes the patient's hair fall out, induces nausea, and so on. I was sufficiently concerned about the potential toxicity for a post-transplant patient such as myself that I brought the issue to the attention of the Johns Hopkins oncologist. He did not exactly endorse the idea, but it also raised no red flags for him. [But he did raise a red flag over Velcade; read on.]

Technically, CyBorD is a protocol approved for newly-diagnosed myeloma patients, rather than as salvage therapy for relapsed patients. But because I have never before been exposed to Velcade, I might be expected to respond to it as if I was a treatment virgin. Its operation is fundamentally different from that of Revlimid, which simply destroys myeloma cells outright. Velcade is more subtle, disrupting the internal processes of cell growth and division, thus preventing myeloma cells from behaving effectively as, well, myeloma cells. The principal danger of Velcade for me is the potential for increased peripheral neuropathy. Weekly subcutaneous injections, rather than twice-weekly IV (the original method of Velcade administration) is supposed to minimize this, but it will have to be carefully monitored.

[Not as of 10/30/13. Instead, the next-generation successor to Velcade/bortezomib, Kyprolis/carfilzomib, will be substituted for it. Peripheral neuropathy is evidently much less of a risk with this agent, which is the primary reason for the switch. It took quite awhile for the medical insurance company to swallow this change, because technically I am not supposed to get carfilzomib until I have failed bortezomib. The Christiana oncologist had to fight an extended battle to get the required authorization to move forward with it; hence the delayed nature of this post. This peripheral neuropathy risk was something that the Hopkins oncologist warned against when I discussed CyBorD with him; I believe he may have influenced the Christiana oncologist's decision to seek this modification.]

This is a complicated protocol, about which I have much more to learn. I will be taking pills (the dex), getting subcutaneous injections of Velcade getting Kyprolis via IV, and getting Cytoxan via IV, each on its own schedule. The first step in the process will be to attend a class at the oncologists' office to find out what is going to happen, and what I will be expected to do; the new campaign will begin the next day. This will occur in the coming week.

I will also be continuing with bisphosphonate therapy, but I am being switched from Aredia to Zometa. I will be learning about this as well.

Meanwhile, I am very happy with the current pain management regimen, which combines dexamethasone with slow-release Oxycontin. I struggle with waking up a couple of times each night, and some of my work days recently have begun at 4 AM, but my appetite is great, and my energy levels are very high.

Thursday, October 10, 2013

Hopkins: No Second Transplant

On Thursday October 10 we made our way to Baltimore to visit the director of the stem cell transplant program at Johns Hopkins. He is not in favor of performing a second transplant on me. In fact, he says that in many cases he has begun to discourage the use of even first-time transplants, in favor of some of the novel chemotherapeutic agents that have appeared in recent years. He specifically mentioned pomalidomide and carfilzomib, both of which I have discussed in earlier posts. Compared with them, a second transplant, and for that matter increasingly even a first transplant, does not do so well in cost/benefit terms -- where "cost" is an expression not so much of money but of risks, side effects, and recovery time; and "benefit" is an expression of the quality of the response and the time to progression. To use his formulation, the novel agents are gradually transforming "a bad nasty disease that kills people" into "a bad nasty chronic condition". They are in no sense curative. But we'll have to take what we can get.

He will communicate his views to my Christiana oncologist, who I am scheduled to visit next week.

Obviously I am relieved by this verdict. None of the proposed regimens will involve anything like the ructions that would be caused by a transplant. I think Huong may be even happier than I am about it; after I started talking about the possibility of a second transplant, I thought I heard her get her suitcases out to start packing.

Meanwhile, daily life has not remained on hold. I continue to work, and I am eating and sleeping normally (although the dexamethasone has me a bit wired, and is causing night sweats). The dexamethasone is doing a good job of keeping down the pain. I can still drive motor vehicles. I confess to not having returned to my normal fitness regimen, as I'm a bit paranoid about the spinal deterioration. Since the myeloma is no longer under control, that cannot be doing anything other than getting worse. Huong is encouraging me to investigate aquatic therapies, which seems like a good low-impact idea.

Tuesday, October 8, 2013

An Unplanned Hospital Stay

The insidious nature of myeloma has revealed itself once again, as if we needed to be reminded of it. A couple of weeks before my visit with the oncologist last month, I began to experience some new pain in the right hip and upper right leg. The pain was hardly debilitating, but it was noticeable, and I mentioned it to the oncologist. She ordered an MRI of the lumbar spine, which revealed some new lesions, indicating myeloma activity. "But we have to give the higher dosage of Revlimid a chance to work", she said. Meanwhile, the new pain remained, but it didn't seem to be spreading or getting worse.

Until late last week, that is. On Thursday October 3, I began feeling not so well during the day, with pain spreading up into the old problem areas of the thoracic spine and lower ribs. But what was really disturbing was that by that evening I was experiencing faint echoes of the spasms that sent me to the hospital for the first time, four years ago.

So we dropped all of our Friday plans in favor of an impromptu visit to the oncologist's office. She quickly settled on the need for a thoracic MRI -- exactly what I was hoping for. But my timing was terrible. The cancer clinic is not a 24x7 operation, and there was no possibility of getting the MRI there before the imaging department shut down for the weekend. Not wanting to just send me home until Monday in a potentially dangerous state, she sent me to the hospital instead.

Miraculously, the ER was practically deserted on a Friday afternoon, and I was more or less swiftly admitted into the hospital and installed in a bed in the Oncology ward. The oncologist stopped by on her way to begin a week-long vacation -- bad timing again -- to announce that "We're done with Revlimid" -- but that she had not yet decided on the treatment path forward.

The neurosurgeon who had done the original balloon kyphoplasty on T8, and who has been monitoring me sporadically ever since, also stopped by to say that he would not be working that weekend, but that he would need to look at the results of the yet-to-be-done MRI, and in any case any necessary surgery would have to wait until the following week. As it happened, I was summoned to appear before the MRI machine not long after his departure.

And then I sat in my hospital room for two days, while nothing else happened, either good or bad. Of course Huong spent a lot of time with me, and she and the iPad together succeeded in keeping me from going mad with boredom.

On Monday October 7, the neurosurgeon called to announce that, while the thoracic MRI showed new lesions and additional compression, there were no new spinal fractures. He indicated that he was unwilling to undertake any surgical procedures whatsoever in my case at present, as any such procedures would be very invasive, involve much recovery time, and could not be counted on to be actually beneficial. His preferred strategy would be to manage my pain while minimizing further damage, i.e. by forcing back the cancer again.

The ball was now firmly in the court of my oncologist's backup -- a man I have never met and have spoken to exactly once, on the phone. He began by telling me what I already knew, that there are now many chemotherapeutic agents available for use against myeloma, and choosing amongst them would be an educated guessing game. And then he hit me with something completely unexpected: "But if I was conducting your case, I would consider a second transplant, because you are still young and strong enough to handle it, and you responded very well to the first one, which would lead me to believe that a second one would be your best chance for another extended remission."

I was frankly speechless, but eventually managed to reply that the Johns Hopkins transplant artists had already expressed their opposition to so-called tandem transplants. To which the backup oncologist replied, "There is little evidence that tandem transplants are sufficiently beneficial, but that is not what we are talking about here. A tandem transplant involves a brief recovery time between the transplants; they are done back to back. Your first transplant was four years ago. This would just be a second transplant." As it happens, I have already set up a near-future appointment with the director of the Hopkins transplant program to discuss the recent developments in my case, and when I told the oncologist this he said, "Excellent. Ask him if he can do another transplant."

So that is my current plan. I am going to ask the Hopkins oncologist if he wants to subject me to the unspeakable horrors of the peripheral blood stem cell transplant a second time.

Meanwhile, I was discharged from the hospital on Monday evening. The pain is being kept at bay with 4 mg doses of my old steroid friend dexamethasone, taken twice daily, which suppresses any swelling of the spinal cord; and I have oxycodone for breakthrough pain relief.

Saturday, September 28, 2013

Daratumumab: The First Myeloma "Breakthrough Therapy"

I haven't been keeping up with my myeloma research in recent months, but I'm making up for lost time now.

In 2012, the Food and Drug Administration Safety and Innovation Act (FDASIA) was enacted. Section 902 created a new category of "breakthrough therapies" that the FDA is supposed to accelerate through its approval process, so that they can reach patients much sooner than would ordinarily be the case. These therapies must represent significant improvements over existing therapies in the treatment of serious or life-threatening conditions. Since at least some clinical evidence of improvement must be demonstrated in advance, the requirements for the "breakthrough" designation are more stringent than for the older alternative "fast track" designation, which can be granted based on preclinical evidence, if the therapy "fills an unmet medical need", i.e. there are no existing therapies at all. At least in theory, a breakthrough therapy could be released to patients after Phase 1 or 2 clinical trials.

In May 2013, the FDA designated daratumumab a breakthrough therapy against refractory myeloma, i.e. myeloma that has become resistant to the existing mainstream therapies, such as bortezomib and lenalidomide.

Phase 2 trials were announced earlier this month.

Friday, September 27, 2013

2013 Test Data

The most recent round of tests had mixed results. Monoclonal proteins continued their upward march, but Kappa free light chains declined. I am in the middle of only the second cycle of the increased 25mg Revlimid dosage, so we must give that time to work. Another UPEP test was also done; this failed to show enough protein concentration to allow UPEP evaluation, which is a good thing.

Here is a summary of the tests so far this year. Note that anything other than "None" is undesirable for the monoclonal proteins; the normal range for Kappa free light chains is 3.3 - 19.4 mg/L, and for the Kappa/Lambda ratio, it is 0.26 - 1.65.

Test DateMonoclonal Spike (g/dL)Kappa Free Light Chains (mg/L)Kappa/Lambda Ratio

Tuesday, August 13, 2013

Le Bleu et le Blanc (apologies to M. Stendhal)

As everyone knows, before being brought under control the cancer did substantial damage to my spine, with the result that I require the use of a cane to walk any distance. Consequently, I am in possession of an official blue-and-white handicapped parking pass, property of the State of Delaware. I would give anything to get my pre-cancer physique back (not that it was any great shakes, but I miss it just the same), but I have learned over time that my "cripple card" is the key to previously unsuspected benefits the world over. So now I always make sure I have it with me whenever I am traveling, even if I have no expectation of driving or parking in the course of my sojourn.

When I arrive at the airport, I have my card handy, because if I have to check luggage, and there is any kind of line for economy ticket holders (I am always one of those), if I wave the card around then typically I, along with my entire "entourage", will be directed into what is invariably a much shorter line for first class customers. I have never discovered the card to be in any way helpful in the security line. But at the gate, if I make myself known to the agents ahead of time, they will instruct me to join the priority boarding group. I have even had the experience of a gate agent rounding me up just prior to the first boarding announcement, and escorting me personally to the boarding pass check machine. How sweet is that?

In France, a ticket seller at a museum or other attraction has only to catch the merest glimpse of the blue-and-white card to immediately punch out, without further ado, two free tickets, one for myself and one for Huong. If there is a temporary exhibit requiring distinct tickets then I can get a couple of those as well.

The French are reputed to have practically invented the modern concept of "bureaucracy", and to have granted us the privilege of incorporating into our language the term unaltered; whereas the Italians are alleged to be intentionally lackadaisical towards (actually quietly contemptuous of) bureaucratic rules and procedures. Yet in this small area these nations seem to have exchanged their stereotypical roles, because in Italy, unlike in France, the blue-and-white card was occasionally carefully scrutinized, and certain of its details, along with those of the supporting Delaware ("The First State") driver license, were entered into one or more Italian databases. I have no idea why, although I speculate that this represents some attempt to head off the potential abuse of the card's substantial benefits, which were much the same in Italy as in France.

To me, the true advantage of the card has to do, not so much with free tickets (as attractive as they are), as with the ability to skip long lines of weary, sweaty tourists. Approaching the Colosseum or the Uffizi on a hot day at the height of the summer tourist season is a daunting prospect. The very long line of people seeking tickets makes the siren song of the tour guides ("skip the line") seem irresistible; but not to me, because I simply march past all of them directly to the Reserved Ticket window (or the Guided Tours entrance, or whatever it is), where eventually I am duly handed my free tickets, and then I... walk in. My companions may have to pay full price for their tickets, but they are at least spared the wait as well.

Incidentally, in some other respects the Italians lived up to their reputation for administrative carelessness. In the course of our recent visit we rode Italian intercity trains three times, and our tickets were checked only once (Typical occurrence: Conductor slouches into car, checks a few tickets, receives cell phone call, wanders off, is never seen again). We used the water buses of Venice for several days, and I was checked just once. In Venice the blue-and-white card was the only artifact I needed to use the water buses; there was no need even to parlay it into any sort of free pass or ticket. I think I'll be going back.