A note on capitalization: I've noticed that I'm not at all consistent in capitalization of blog post titles. I'll try to at least be slightly conscious of that in the future, but I do try to be consistent in capitalizing (or not) drug names: brand names (Ninaro, Revlimid, Darzalex, etc.) are capitalized, generic names (ixazomib, lenalidomide, daratumumab) are not. I'm convinced that pharma companies have committees whose sole job is to make generic names that are both unpronounceable and at best only vaguely related to molecular function, but that's not why we're here. We're here to bury the lede. Done!
As I have continued to enjoy good health, 3 years out from my second stem cell transplant, my complaints have less to do with multiple myeloma and more to do with being a 60 year old guy with some issues. The latter is a far less compelling reason to be blogging, it seems to me, than the former. Nevertheless I will persist and sometimes the one thing comes around to the other in a way that may be trying to tell us something.
My tears are toxic. I hardly have to say that the temptation to make this into some kind of metaphor is overwhelming, but I'm not going there.
For many years I've had rosacea, a pretty common skin condition that I've always considered (with no particular evidence) a long-term consequence of the bad acne I had as an adolescent/young adult. Over the years it would wax and wane, and I had been taking low-dose doxycycline to control the rosacea for some years before I was diagnosed with MM. It worked pretty well. After the stem cell transplants, I resumed doxycycline for a year as prophylaxis against bacterial infections. Two years ago, the docs decided I didn't need the prophylaxis any more, and I figured I could probably give my liver a break at the expense of my vanity, so I quit taking doxycycline. I replaced it with some topical stuff (metronidazole, azelaic acid) that sometimes seemed to help.
Over time, the redness and lesions increased in number and frequency. And a pattern appeared. Lines ran down my cheeks on either side of my nose, and frequently around the base of my nose. When things got bad, they'd radiate outward, but the focus was always around my nose. Meanwhile, my eyes were tearing more often and more regularly than ever before. Tears seemed to be implicated, because the rosacea was occurring right along the paths down which the tears ran, both outside and inside my nose. Often there's a clear pattern running right from the tear ducts down to the corners of my mouth.
Chemotherapy agents are absorbed into all kinds of tissues, processed in various ways, and emerge via bodily fluids of one kind or another. Mostly it's going to be urine or feces, or blood if you're bleeding, but sweat, mucus, semen, and tears also can carry the chemo agents or their downstream products. It turns out that both Revlimid and especially Ninlaro are associated with rashes and skin lesions, and excessive tearing is a common side effect of proteasome inhibitors (like Ninlaro). So I think my excessive tears, carrying enough residual Ninlaro and Revlimid to cause my already-reactive skin to become inflamed, stimulate the latter-day "rosacea." The topical treatments I've been using, while they allegedly have some anti-inflammatory effects, are probably not up to the task of dealing with this level of inflammation, so I'm going to try steroids like cortisone for a while. The early results are encouraging.
As for the metaphor, it would be way over the top. I'm as given to tears as the next guy (maybe more so), especially when they ramp up the music at the end of the movie--being fully aware that I am being cruelly manipulated makes me want to cry--but I am not in any way despondent about my circumstances, as I hope this blog makes clear. That's subject to change, of course, but I now have an objective reason to avoid tears, even if I may not be able to do much to stop them.
Friday, December 6, 2019
Tuesday, November 12, 2019
New drugs
A preface to this post: last year, in reviewing my options for Medicare coverage (surely one of the driest sets of posts I've done--at least I hope so!), I made a post with the title "Drugs." Didn't think twice about it. Every so often I check to make sure there are at least a few people still reading: the few, the proud . . .
Anyhow, one post stands out for alleged readership, with roughly ten times more hits than average. You guessed it---"Drugs." So, in the spirit of experimentation, I've got a new really dry subject to cover, namely new MM drugs just approved and in the pipeline, and I'm pretty sure that I can boost my stats just by putting the word drugs in the title of the post. Sorry, everyone who is trolling for mind-altering substances. Nothing to see here. You've heard of the dark web?
I'm not planning any changes to the current chemo regimen (Ninlaro, Revlimid, dexamethasone), since it's working very well at present, but there's no reason to think it will work indefinitely, so I keep an eye on new developments in the pharma pipeline. Myeloma is proving to be fertile ground for drug discovery and there are lots of interesting things out there, including one new FDA approval and several that are pretty far along in clinical trials--in fact, there are so many different approaches that seem to be bearing fruit that it seems like a kind of golden age in myeloma treatment. Golden ages are best judged after many years have passed, of course, so maybe it's just a lighter version of the darker ages that have gone before. But there is real progress--hard to judge while you are in the midst of it--but undeniable.
For example: in this post, the proportion of patients like me ("high-risk") surviving for a standard treatment (Single ASCT) is about 30%, 4 years after diagnosis [For the record, I am just about exactly 4 years post-diagnosis.] Given what we knew at the time, we chose a second transplant, and that seems to have been a wise choice. But that barely scratches the surface of what has changed over the last few years.
Most of what is new is that a bunch of different attacks on myeloma cells look to be working. I wanted to say "are bearing fruit", but that's almost exactly wrong. Tumor fruit is not to be borne. In any case, here's a quick rundown of what's newish.
1) Xpovio (that's the brand name), selinexor (that's the generic name). The only new FDA-approved drug for MM since 2015. An interesting story in several respects: 1) new mechanism--the drug interferes with nuclear export within cells, meaning that cells can't get the new stuff they've made out of their nuclei fast enough, leading to death; 2) it works comparatively well for patients who have exhausted all other possibilities, including those like me who are considered high-risk; and 3) it almost didn't get approved because there were a surprising number of unexpected patient deaths, balanced against the bleak prospects of those patients if they had no other options.
2) Monoclonal antibodies. Back in 2015, two monoclonal antibodies were approved by FDA. One, daratumumab (brand name Darzalex), has been a big winner in terms of patient responses, market share, and name recognition. It targets CD38, an antigen that most myeloma tumor cells express. The other, elotuzumab (Empliciti) targets a different antigen (SLAMF7), and also looks to be working well, but needs a bit of help from some of the other myeloma drugs. One major thing about the the monoclonal antibodies is that they have some major effect by themselves, but they can also be used to target anything from chemotherapy agents, to biologics, to nuclear warheads (really!) that will attack the tumor cells. More on this to come.
3) CAR-T. There are something like a half-dozen trials of chimeric antigen receptor T-cell (CAR-T) therapies in MM, and most of them look really good so far. The idea is that you harvest T-cells from the patient, culture them in the lab and attach a new receptor to the T-cells that will more-or-less specifically recognize a myeloma tumor, attach to it, and kill it. As of today, CAR-T therapies have been approved for some leukemias and some lymphomas. The upside is that they might actually cure the disease. The downside is that they are so expensive ($500k+) that they have not been widely adopted so far.
In myeloma, the trials so far have yielded very positive results, even in patients who have failed multiple rounds of treatment. It seems likely that approvals for one or more of these will be granted within a year or two. The expense issue will still be there, and the competition might be fierce, but I am looking forward to having this as an option.
Just this week, the abstracts for the December 2019 American Society of Hematology meetings have been released. It looks like several of the CAR-T trials that have been in progress have continued to have great results.
4) BiTE. Bi-specific T-cell engager. A newer, potentially much cooler approach is to make compounds that have myeloma-specific antigens on one end, and T-cell targets on the other. These function as matchmakers, bringing together the presumably fatal attraction between the tumor cells and the T-cells. Unlike CAR-Ts, they don't need cells cultured from the patients, a big plus. So far, there is a big minus as well, because the half-life of the BiTEs is very short, so in trials patients have needed to be infused continuously for 28 days. That would be hard.
I haven't seen any updates yet for this trial, but I will post them if/when I do.
There's a similar new technology, called T-cell effectors, that are also showing promising early results. The idea is similar--the molecule is engineered to bring together the antigens on the tumor with the T-cells that will kill them.
5) CRISPR. The first human cancer trials of a CRISPR-based approach to treatment for myeloma have just begun at the University of Pennsylvania, with two myeloma patients and one lymphoma patient enrolled. The good news is that all the patients are still alive after 9 months, and the edited cells are still present. It's way too early to say how this will go, but so far it's looking good.
6) Conjugates. This is a rapidly growing area, in which a monoclonal antibody targeted to some tumor antigen (CD38, BCMA, etc.) is used to introduce something toxic to the tumor cells. There are a huge number of possibilities, from basic toxins to apoptosis-inducers to radioactive compounds. Definitely an area to watch (the approach could work for many cancers).
7) The stuff that's already approved, but I haven't needed it yet. This is a pretty big list by now. It's headed by Darzalex and Empliciti, but there are other newly approved drugs that could replace drugs I already take if they fail. The Ninlaro could be replaced by Kyprolis, Revlimid by Pomalyst. Sadly, there is no better replacement for my particular nemesis, dexamethasone.
As long as the current regime keeps me in the complete response category, and the Rube Goldbergian system that pays pharmaceutical companies too much for their highly variable investments in research and (especially) development continues to pay out, I have the luxury of waiting out the results of these many, many studies.
More to come.
Anyhow, one post stands out for alleged readership, with roughly ten times more hits than average. You guessed it---"Drugs." So, in the spirit of experimentation, I've got a new really dry subject to cover, namely new MM drugs just approved and in the pipeline, and I'm pretty sure that I can boost my stats just by putting the word drugs in the title of the post. Sorry, everyone who is trolling for mind-altering substances. Nothing to see here. You've heard of the dark web?
I'm not planning any changes to the current chemo regimen (Ninlaro, Revlimid, dexamethasone), since it's working very well at present, but there's no reason to think it will work indefinitely, so I keep an eye on new developments in the pharma pipeline. Myeloma is proving to be fertile ground for drug discovery and there are lots of interesting things out there, including one new FDA approval and several that are pretty far along in clinical trials--in fact, there are so many different approaches that seem to be bearing fruit that it seems like a kind of golden age in myeloma treatment. Golden ages are best judged after many years have passed, of course, so maybe it's just a lighter version of the darker ages that have gone before. But there is real progress--hard to judge while you are in the midst of it--but undeniable.
For example: in this post, the proportion of patients like me ("high-risk") surviving for a standard treatment (Single ASCT) is about 30%, 4 years after diagnosis [For the record, I am just about exactly 4 years post-diagnosis.] Given what we knew at the time, we chose a second transplant, and that seems to have been a wise choice. But that barely scratches the surface of what has changed over the last few years.
Most of what is new is that a bunch of different attacks on myeloma cells look to be working. I wanted to say "are bearing fruit", but that's almost exactly wrong. Tumor fruit is not to be borne. In any case, here's a quick rundown of what's newish.
1) Xpovio (that's the brand name), selinexor (that's the generic name). The only new FDA-approved drug for MM since 2015. An interesting story in several respects: 1) new mechanism--the drug interferes with nuclear export within cells, meaning that cells can't get the new stuff they've made out of their nuclei fast enough, leading to death; 2) it works comparatively well for patients who have exhausted all other possibilities, including those like me who are considered high-risk; and 3) it almost didn't get approved because there were a surprising number of unexpected patient deaths, balanced against the bleak prospects of those patients if they had no other options.
2) Monoclonal antibodies. Back in 2015, two monoclonal antibodies were approved by FDA. One, daratumumab (brand name Darzalex), has been a big winner in terms of patient responses, market share, and name recognition. It targets CD38, an antigen that most myeloma tumor cells express. The other, elotuzumab (Empliciti) targets a different antigen (SLAMF7), and also looks to be working well, but needs a bit of help from some of the other myeloma drugs. One major thing about the the monoclonal antibodies is that they have some major effect by themselves, but they can also be used to target anything from chemotherapy agents, to biologics, to nuclear warheads (really!) that will attack the tumor cells. More on this to come.
3) CAR-T. There are something like a half-dozen trials of chimeric antigen receptor T-cell (CAR-T) therapies in MM, and most of them look really good so far. The idea is that you harvest T-cells from the patient, culture them in the lab and attach a new receptor to the T-cells that will more-or-less specifically recognize a myeloma tumor, attach to it, and kill it. As of today, CAR-T therapies have been approved for some leukemias and some lymphomas. The upside is that they might actually cure the disease. The downside is that they are so expensive ($500k+) that they have not been widely adopted so far.
In myeloma, the trials so far have yielded very positive results, even in patients who have failed multiple rounds of treatment. It seems likely that approvals for one or more of these will be granted within a year or two. The expense issue will still be there, and the competition might be fierce, but I am looking forward to having this as an option.
Just this week, the abstracts for the December 2019 American Society of Hematology meetings have been released. It looks like several of the CAR-T trials that have been in progress have continued to have great results.
4) BiTE. Bi-specific T-cell engager. A newer, potentially much cooler approach is to make compounds that have myeloma-specific antigens on one end, and T-cell targets on the other. These function as matchmakers, bringing together the presumably fatal attraction between the tumor cells and the T-cells. Unlike CAR-Ts, they don't need cells cultured from the patients, a big plus. So far, there is a big minus as well, because the half-life of the BiTEs is very short, so in trials patients have needed to be infused continuously for 28 days. That would be hard.
I haven't seen any updates yet for this trial, but I will post them if/when I do.
There's a similar new technology, called T-cell effectors, that are also showing promising early results. The idea is similar--the molecule is engineered to bring together the antigens on the tumor with the T-cells that will kill them.
5) CRISPR. The first human cancer trials of a CRISPR-based approach to treatment for myeloma have just begun at the University of Pennsylvania, with two myeloma patients and one lymphoma patient enrolled. The good news is that all the patients are still alive after 9 months, and the edited cells are still present. It's way too early to say how this will go, but so far it's looking good.
6) Conjugates. This is a rapidly growing area, in which a monoclonal antibody targeted to some tumor antigen (CD38, BCMA, etc.) is used to introduce something toxic to the tumor cells. There are a huge number of possibilities, from basic toxins to apoptosis-inducers to radioactive compounds. Definitely an area to watch (the approach could work for many cancers).
7) The stuff that's already approved, but I haven't needed it yet. This is a pretty big list by now. It's headed by Darzalex and Empliciti, but there are other newly approved drugs that could replace drugs I already take if they fail. The Ninlaro could be replaced by Kyprolis, Revlimid by Pomalyst. Sadly, there is no better replacement for my particular nemesis, dexamethasone.
As long as the current regime keeps me in the complete response category, and the Rube Goldbergian system that pays pharmaceutical companies too much for their highly variable investments in research and (especially) development continues to pay out, I have the luxury of waiting out the results of these many, many studies.
More to come.
Tuesday, August 27, 2019
bad science
In my last post, I noted that there were, among the projects, a number of studies of how family history affected risk of various diseases. These were built around some methods that Liz and I developed for querying genealogical databases, primarily the Utah Population Database, fondly referred to as the UPDB. The UPDB provided huge numbers of connections between people over multiple generations, but was hit-or-miss with the disease data that was needed to connect people with the same condition. The cancer data was excellent, thanks to longstanding connections to the statewide cancer registry. Heart disease, stroke, diabetes, Alzheimers, and many (most) others, though, were only available with the help of clinical enterprises, most of which had financial and competitive interests that frequently impeded research.
Over time, we developed some approaches that allowed for reasonable conclusions to be drawn about smaller clinical datasets, and a steady trickle of physicians brought data to us for analysis. Among these were a number of fine physician-scientists with whom it was a pleasure to work.
Not all of them, however. Shortly before we left Utah for Louisville, I worked with an ophthalmologist who had a fairly typical clinical series of patients with age-related macular degeneration, a leading cause of visual impairment and blindness among older folks.
As was the norm, I identified the relatives of his patients, including which of them were also affected, and computed the relative risks (compared to controls), and the usual supporting statistics, wrote the bulk of the Methods and Results sections of the resulting paper, and contributed commentary about the wider implications. For some reason he felt my contribution was not worth noting, however, and he sent off his draft, got it accepted and published, without my name on the author list.
If you're not listed as an author, of course, you don't participate in any correspondence with the journal or its editors. Nor is it the practice of any university oversight committee to query all the faculty not listed as authors to make sure no one was left off the list. So I didn't see this paper until it came out. I wrote a strongly-worded email to this ophthalmologist (he's the senior author--the one listed last), cc'd to higher-ups at the university, and extracted a promise to revise the online publication to correctly reflect my contribution. The principle mattered more to me than this particular publication, and I promptly forgot about the entire incident.
Until I saw this headline. It seems that what goes round comes round, at least if you go far enough around. I especially liked this line from The Scientist: "Zhang’s poor record of disclosing conflicts of interest accompanies a sketchy past of putting patients and research participants at risk during his work."
That and apparently being some kind of spy. In comparison, my beef about authorship is pretty small. But I think the view into his character afforded by that minor incident was clear enough, and I was not at all surprised that someone who can so easily step on a colleague has no compunction about abusing his patients.
[By the way, it's clear in the first link above that he lied about contacting the journal. Saves me the embarrassment of having co-authored a paper with him.]
Over time, we developed some approaches that allowed for reasonable conclusions to be drawn about smaller clinical datasets, and a steady trickle of physicians brought data to us for analysis. Among these were a number of fine physician-scientists with whom it was a pleasure to work.
Not all of them, however. Shortly before we left Utah for Louisville, I worked with an ophthalmologist who had a fairly typical clinical series of patients with age-related macular degeneration, a leading cause of visual impairment and blindness among older folks.
As was the norm, I identified the relatives of his patients, including which of them were also affected, and computed the relative risks (compared to controls), and the usual supporting statistics, wrote the bulk of the Methods and Results sections of the resulting paper, and contributed commentary about the wider implications. For some reason he felt my contribution was not worth noting, however, and he sent off his draft, got it accepted and published, without my name on the author list.
If you're not listed as an author, of course, you don't participate in any correspondence with the journal or its editors. Nor is it the practice of any university oversight committee to query all the faculty not listed as authors to make sure no one was left off the list. So I didn't see this paper until it came out. I wrote a strongly-worded email to this ophthalmologist (he's the senior author--the one listed last), cc'd to higher-ups at the university, and extracted a promise to revise the online publication to correctly reflect my contribution. The principle mattered more to me than this particular publication, and I promptly forgot about the entire incident.
Until I saw this headline. It seems that what goes round comes round, at least if you go far enough around. I especially liked this line from The Scientist: "Zhang’s poor record of disclosing conflicts of interest accompanies a sketchy past of putting patients and research participants at risk during his work."
That and apparently being some kind of spy. In comparison, my beef about authorship is pretty small. But I think the view into his character afforded by that minor incident was clear enough, and I was not at all surprised that someone who can so easily step on a colleague has no compunction about abusing his patients.
[By the way, it's clear in the first link above that he lied about contacting the journal. Saves me the embarrassment of having co-authored a paper with him.]
Monday, August 26, 2019
Projects
The reality of my projects has been called into question--recently, but also on many prior occasions--and, as a more-or-less recently retired professor, I am here to defend them.
In academics, as in life, projects can take many forms. For me and many others in biomedical research, the classic pattern has been: 1) develop an idea; 2) do some preliminary research at little or no cost; 3) if the idea seems to have some support, try to get funding to do a larger-scale study; 4) publish the results; 5) iterate steps 3 and 4 for as long as possible, perhaps an entire career.
For the record, you can see how this looks in my case by clicking here. The number of publications is less important than the number of citations, which indicate that someone has read your paper and thinks that the research that they have done is in some way indebted to the previous work described in your paper. They may disagree vehemently with your conclusions, but they can't ignore your work. Scientific consensus arises from scientific argument; nothing gets you ahead in your career faster than disagreeing with the conventional wisdom and actually being right. Actually, "faster" isn't the right adjective. "Farther" is better. Lister, Mendel, Gallileo, McClintock, and many others did not achieve success in the short term. (The trick is that the conventional wisdom in science is very often right.)
I've started, finished, and contributed to all kinds of scientific projects over the years, ranging from assessments of the degree to which fallout from nuclear weapons testing caused cancer and other diseases in Utahns living downwind, to (many) studies of the utility of family history as a predictor of disease risk, to studies of molecular markers of aging . . . and numerous other projects inspired by collaborations with physicians, fellows, and students over the years.
The majority of projects don't get past step 1 or 2, but that doesn't mean they don't have merit. In fact, the early stages of putting together ideas and data, doing preliminary statistical analysis and seeing early results is usually more fun and rewarding than writing up papers for publication, preparing grant proposals, and even getting an award and making the dream project a reality.
At present, Liz and I are working on preliminary data and writing up results for several projects that have been or will be turned into grant proposals. We're doing this pro bono, which gives us the freedom to pick our spots and keep our priorities straight.
Of course I've had lots of projects over the years that didn't have anything much to do science: co-raising children, managing finances, house and yard maintenance, travel, pointless tinkering with electronics and software, etc.
Being a cancer patient is also a project--make no mistake: there are daily, weekly, monthly, and annual cycles of medications, blood tests, X-rays, and consultations. Every month requires a new prescription, a telephone order complete with nurse consultation, a check of the insurance status for said order, and a consideration of any travel plans for the next month, since a street address and delivery signature are required. The process is not especially hard or complicated, but it is always front and center and cannot be ignored.
And then, sometimes, I write about my experiences and associated thoughts. At Christmas I took all the posts from the beginning of this blog and formatted them into a book, to give to my mother and others who weren't going to be reading blog posts. The result was a slender volume of about 100 pages--not monumental, to be sure, but a satisfyingly tactile indicator of having done something.
Dog raising is another project. I'm pretty sure that it becomes less of a project as your dog becomes better trained. Suffice it to say that Sunny is still a small dog, but a big project.
And we've added a new project/family member: a tiny teardrop trailer ready for road trips. Mostly it won't require much work on our part, but I will need to improve my trailer-backing skills.
In academics, as in life, projects can take many forms. For me and many others in biomedical research, the classic pattern has been: 1) develop an idea; 2) do some preliminary research at little or no cost; 3) if the idea seems to have some support, try to get funding to do a larger-scale study; 4) publish the results; 5) iterate steps 3 and 4 for as long as possible, perhaps an entire career.
For the record, you can see how this looks in my case by clicking here. The number of publications is less important than the number of citations, which indicate that someone has read your paper and thinks that the research that they have done is in some way indebted to the previous work described in your paper. They may disagree vehemently with your conclusions, but they can't ignore your work. Scientific consensus arises from scientific argument; nothing gets you ahead in your career faster than disagreeing with the conventional wisdom and actually being right. Actually, "faster" isn't the right adjective. "Farther" is better. Lister, Mendel, Gallileo, McClintock, and many others did not achieve success in the short term. (The trick is that the conventional wisdom in science is very often right.)
I've started, finished, and contributed to all kinds of scientific projects over the years, ranging from assessments of the degree to which fallout from nuclear weapons testing caused cancer and other diseases in Utahns living downwind, to (many) studies of the utility of family history as a predictor of disease risk, to studies of molecular markers of aging . . . and numerous other projects inspired by collaborations with physicians, fellows, and students over the years.
The majority of projects don't get past step 1 or 2, but that doesn't mean they don't have merit. In fact, the early stages of putting together ideas and data, doing preliminary statistical analysis and seeing early results is usually more fun and rewarding than writing up papers for publication, preparing grant proposals, and even getting an award and making the dream project a reality.
At present, Liz and I are working on preliminary data and writing up results for several projects that have been or will be turned into grant proposals. We're doing this pro bono, which gives us the freedom to pick our spots and keep our priorities straight.
Of course I've had lots of projects over the years that didn't have anything much to do science: co-raising children, managing finances, house and yard maintenance, travel, pointless tinkering with electronics and software, etc.
Being a cancer patient is also a project--make no mistake: there are daily, weekly, monthly, and annual cycles of medications, blood tests, X-rays, and consultations. Every month requires a new prescription, a telephone order complete with nurse consultation, a check of the insurance status for said order, and a consideration of any travel plans for the next month, since a street address and delivery signature are required. The process is not especially hard or complicated, but it is always front and center and cannot be ignored.
And then, sometimes, I write about my experiences and associated thoughts. At Christmas I took all the posts from the beginning of this blog and formatted them into a book, to give to my mother and others who weren't going to be reading blog posts. The result was a slender volume of about 100 pages--not monumental, to be sure, but a satisfyingly tactile indicator of having done something.
Thursday, August 15, 2019
N of one
It turns out that N-of-one trials are a thing. Back in the early days of this blog, I described the basic idea and naming principle--that my experience with treatment would be its own experiment, controlled to some degree by my pre- and post-treatment experiences.
I have been carefully recording many variables, but not quite with the rigor that would be required to do a formal trial. I've been focused on labs, and thinking about exposures, but haven't been good about recording exposures (diet, alcohol, probiotics, dog, travel, weather, etc.). I expect that, soon, N-of-one trials will answer lots of questions about how individual variation (in genetics, epigenetics, microbiome) interacts with exposures to make people sick (or not).
But the labs are good! Here's a picture, very much like the last (many) pictures, but produced by a website, all4cure.com, started by an oncologist who found himself diagnosed with multiple myeloma. The data transfers are definitely not as easy as they could be, but it's working, to what effect I'm not quite sure. The graphs are fairly nice, though.
I don't know how long this particular drug regimen will continue to be effective--no one does, because I was an early adopter. If Medicare and marrow continue to support it, I am not going to complain.
I have been carefully recording many variables, but not quite with the rigor that would be required to do a formal trial. I've been focused on labs, and thinking about exposures, but haven't been good about recording exposures (diet, alcohol, probiotics, dog, travel, weather, etc.). I expect that, soon, N-of-one trials will answer lots of questions about how individual variation (in genetics, epigenetics, microbiome) interacts with exposures to make people sick (or not).
But the labs are good! Here's a picture, very much like the last (many) pictures, but produced by a website, all4cure.com, started by an oncologist who found himself diagnosed with multiple myeloma. The data transfers are definitely not as easy as they could be, but it's working, to what effect I'm not quite sure. The graphs are fairly nice, though.
I don't know how long this particular drug regimen will continue to be effective--no one does, because I was an early adopter. If Medicare and marrow continue to support it, I am not going to complain.
Thursday, June 13, 2019
Re-mindfulness
One consequence of the continuous chemotherapy regimen is sleeplessness. It's not extreme, and it can be managed with drugs that (probably) don't have terrible long-term consequences, notably Benadryl. But at certain points of the cycle, I can get almost exactly 4 hours of good sleep--and then I am awake, as if I'd just had a double Americano and a slap in the face.
Possibly because of previous experience with the above-named therapies, I am not distressed to find myself in this position at 3 or 4 AM. Sometimes I welcome the quiet and have thoughts that are useful and constructive. Sometimes I reflect on a dream (inevitably weird). Sometimes I can't be totally sure what I've got.
So--I have been introduced to the concept of mindfulness on many occasions, and it has always seemed like the right approach to pretty much everything in life. Especially to driving a car, though that is rarely mentioned. It also has, at various times, seemed just like some cultural buzzword worthy of derision by the broletariat. In any case, mindfulness is not always achieved (I suppose) even by its most enlightened practitioners, and is less often, rarely, achieved by those of us who practice whatever it is we practice.
One recent night, my eyes open in the dark, I thought about several specific moments when I should have been mindful but was not. The consequences of having not been mindful, the possibility that life might have been altered positively had I been so, etc.
Remindfulness! OK, maybe this has been done. I think psych therapists have spent some decades here. But maybe I could do a TED talk? Otherwise, watch out--there could be a whole lot blog posts on this theme. Sorry.
Possibly because of previous experience with the above-named therapies, I am not distressed to find myself in this position at 3 or 4 AM. Sometimes I welcome the quiet and have thoughts that are useful and constructive. Sometimes I reflect on a dream (inevitably weird). Sometimes I can't be totally sure what I've got.
So--I have been introduced to the concept of mindfulness on many occasions, and it has always seemed like the right approach to pretty much everything in life. Especially to driving a car, though that is rarely mentioned. It also has, at various times, seemed just like some cultural buzzword worthy of derision by the broletariat. In any case, mindfulness is not always achieved (I suppose) even by its most enlightened practitioners, and is less often, rarely, achieved by those of us who practice whatever it is we practice.
One recent night, my eyes open in the dark, I thought about several specific moments when I should have been mindful but was not. The consequences of having not been mindful, the possibility that life might have been altered positively had I been so, etc.
Remindfulness! OK, maybe this has been done. I think psych therapists have spent some decades here. But maybe I could do a TED talk? Otherwise, watch out--there could be a whole lot blog posts on this theme. Sorry.
Thursday, June 6, 2019
Love Poems
The late 1970s was in some ways the ideal time to go to college. No one cared about anything (sex, drugs, and rock ‘n roll excepted). There was no war to oppose. There was no war to be called up for. The economy was a mess, but I remember few discussions of what people would be doing when they graduated, with the exception of premeds and the few aiming for Wall Street.
At some point, I found the pond to be too stagnant for my taste. I ran a two-line ad in the college paper that said something like “Tired of apathy? Join Bedrock!” and gave some contact information about a meeting. I think we got 8 people to that first meeting, only 3 were of which were my roommates. The agenda was to get people on campus talking about the global environment, cultural conflicts, energy and feminism.
The name Bedrock came from a poem by Gary Snyder. It’s a love poem, and I’m going to say I knew that, but I have it on better authority than that. I managed to arrange a visit to Kenyon by Snyder some months after founding Bedrock. He was giving a reading at Oberlin and all we had to do was get him a ride from Oberlin to Kenyon on the appointed date. I had a car and a friend, and we snapped to it. I think that was the only longish car trip my ‘73 Audi Fox ever made without breaking down, and I remain slightly, grudgingly grateful for that.
Gary Snyder was the first “famous” person I’d ever met. He’d featured (as Japhy Ryder) in Jack Kerouac’s The Dharma Bums, he’d won a Pulitzer for his poetry, and he was cool beyond belief. He had a hip flask of bourbon—he preferred Rebel Yell, but was settling for J.W. Dant while in Ohio—and he shared with us. Could be the first moment when I though bourbon was worthy of my attention. Oh well.
He asked me about the name Bedrock, noting that it was a love poem. Lamely, I explained that I was trying to establish some kind of foundation for even getting started to get people involved in thinking about what was going to happen next in the world and whether we could do anything to make it better.
He said: “Why the Hell are you guys so diffident?”
We were all that, but maybe that was the difference between 1978 Ohio and 1978 California, and the difference between him and us. And maybe this sounds even more lame, but I am proud of several moments in Bedrock’s history, notably when we had a great panel discussion (40 years ago!) of the conservative case for carbon taxes.
So, love poems. The Kenyon Review had just been revived during those years. I asked Philip Church, poetry editor of the Review, if I could do an independent study with him, and to my surprise he agreed. I had a set of poems I’d written, wrote some more, and met with him weekly in his office. He was generous in his criticism (probably this was not a good sign, although I didn’t get it back then), and we had great, wide-ranging conversations about music, evolution, and even poetry (Loren Eiseley was a touchstone for both of us).
One week I brought him a poem called “Scotch Symphony.” It was a memory of an event from late Spring of my Junior year, when a friend soon to graduate took me to a lake where great blue herons nested. The language in the poem was abstract enough to get Dr. Church intrigued. When I told him it was basically a love poem he was deflated. It did feature whiskey and birds as well, but I guess the love was problematic. To say the least, but that was not in the poem.
I’ve buried the lede again. Love is what it’s all about, people! As I’ve confronted my own mortality (sure I’ve been granted a reprieve, but all we’re--any of us--going to get is a reprieve of one kind or another), I’ve done a fair amount of reflecting on what all the noise and confusion of my life has amounted to: I’ve made some contributions to science, passed some genes on to the next generation, had a few transcendent moments in some sport or other, viewed some spectacular scenery, and so forth. The real experience of life, though, has been to love. The other emotions leave a mark, of course, but when I am lying in a bed and drawing my last, I am hoping to remember the love I’ve felt for all the others: family, friends, colleagues. Romantic love is its own thing, of course—I can’t compare Liz to anyone—whatever shape my brain is in by the end, I know right now that our love is flying out into the universe at 186,000 miles per second and can never be erased. I didn’t even write her a love poem until we’d been married 17 years, but I think there is other evidence out there.
The same goes for my children, both of them. If you truly love your partner, the love you feel for the spawn of that relationship is every bit as intense, if differently conceived. I don’t know how it is if you have less positive feelings for your partner. Might not make that much difference, but I’ve only experienced it the one way, and I am beyond grateful for that.
It’s certainly true that hateful people are frequently remembered long after they die. Who cares about them? We care because we don’t want to follow their example. We may or not be remembered—I would like to be remembered—but it will make no difference to we who are deceased. Better, I think, to feel love in your last moments. I’m going to try.
At some point, I found the pond to be too stagnant for my taste. I ran a two-line ad in the college paper that said something like “Tired of apathy? Join Bedrock!” and gave some contact information about a meeting. I think we got 8 people to that first meeting, only 3 were of which were my roommates. The agenda was to get people on campus talking about the global environment, cultural conflicts, energy and feminism.
The name Bedrock came from a poem by Gary Snyder. It’s a love poem, and I’m going to say I knew that, but I have it on better authority than that. I managed to arrange a visit to Kenyon by Snyder some months after founding Bedrock. He was giving a reading at Oberlin and all we had to do was get him a ride from Oberlin to Kenyon on the appointed date. I had a car and a friend, and we snapped to it. I think that was the only longish car trip my ‘73 Audi Fox ever made without breaking down, and I remain slightly, grudgingly grateful for that.
Gary Snyder was the first “famous” person I’d ever met. He’d featured (as Japhy Ryder) in Jack Kerouac’s The Dharma Bums, he’d won a Pulitzer for his poetry, and he was cool beyond belief. He had a hip flask of bourbon—he preferred Rebel Yell, but was settling for J.W. Dant while in Ohio—and he shared with us. Could be the first moment when I though bourbon was worthy of my attention. Oh well.
He asked me about the name Bedrock, noting that it was a love poem. Lamely, I explained that I was trying to establish some kind of foundation for even getting started to get people involved in thinking about what was going to happen next in the world and whether we could do anything to make it better.
He said: “Why the Hell are you guys so diffident?”
We were all that, but maybe that was the difference between 1978 Ohio and 1978 California, and the difference between him and us. And maybe this sounds even more lame, but I am proud of several moments in Bedrock’s history, notably when we had a great panel discussion (40 years ago!) of the conservative case for carbon taxes.
So, love poems. The Kenyon Review had just been revived during those years. I asked Philip Church, poetry editor of the Review, if I could do an independent study with him, and to my surprise he agreed. I had a set of poems I’d written, wrote some more, and met with him weekly in his office. He was generous in his criticism (probably this was not a good sign, although I didn’t get it back then), and we had great, wide-ranging conversations about music, evolution, and even poetry (Loren Eiseley was a touchstone for both of us).
One week I brought him a poem called “Scotch Symphony.” It was a memory of an event from late Spring of my Junior year, when a friend soon to graduate took me to a lake where great blue herons nested. The language in the poem was abstract enough to get Dr. Church intrigued. When I told him it was basically a love poem he was deflated. It did feature whiskey and birds as well, but I guess the love was problematic. To say the least, but that was not in the poem.
I’ve buried the lede again. Love is what it’s all about, people! As I’ve confronted my own mortality (sure I’ve been granted a reprieve, but all we’re--any of us--going to get is a reprieve of one kind or another), I’ve done a fair amount of reflecting on what all the noise and confusion of my life has amounted to: I’ve made some contributions to science, passed some genes on to the next generation, had a few transcendent moments in some sport or other, viewed some spectacular scenery, and so forth. The real experience of life, though, has been to love. The other emotions leave a mark, of course, but when I am lying in a bed and drawing my last, I am hoping to remember the love I’ve felt for all the others: family, friends, colleagues. Romantic love is its own thing, of course—I can’t compare Liz to anyone—whatever shape my brain is in by the end, I know right now that our love is flying out into the universe at 186,000 miles per second and can never be erased. I didn’t even write her a love poem until we’d been married 17 years, but I think there is other evidence out there.
The same goes for my children, both of them. If you truly love your partner, the love you feel for the spawn of that relationship is every bit as intense, if differently conceived. I don’t know how it is if you have less positive feelings for your partner. Might not make that much difference, but I’ve only experienced it the one way, and I am beyond grateful for that.
It’s certainly true that hateful people are frequently remembered long after they die. Who cares about them? We care because we don’t want to follow their example. We may or not be remembered—I would like to be remembered—but it will make no difference to we who are deceased. Better, I think, to feel love in your last moments. I’m going to try.
Sunday, June 2, 2019
CR
I made a quick trip to Mayo just before Memorial Day, a routine follow-up with blood and urine samples and a C/T scan to make sure my bones were still holding together. The original plan was to drive up to Rochester, with the dog in tow, and continue from there out West as far as Salt Lake City for a wedding and some long-overdue visits with friends. After a quick overnight test trip of ~200 miles, though, we decided that we couldn't do the dog-and-drive thing for two weeks straight without driving ourselves crazy, so we decided we'd better board the dog and fly. We're going to practice traveling with Sunny, and hope to get her as far as Wisconsin, at least, this Summer.
The visit to Mayo was happily uneventful, and confirmed the fact that I am still essentially disease-free at this point. My hematologist (third author on this paper) noted that I now meet the criteria for "complete response," and we figured that I've been there for about a year now. The kappa and lambda numbers keep edging close to one another, and both are in the normal range. The other lab values look fine across the board (platelets a little low, but not alarmingly so). Even my hard-pressed red blood cells have rallied to boost my hemoglobin up into the normal range. My bones are holding together, too--nothing new going on there.Lots of patients would have treatment stopped at this point, but it's not something we're contemplating now. The "high risk" 17p deletion argues against stopping, as does the fact that I'm tolerating all the drugs pretty well. The only change is that I'll start getting Zometa (that's what's keeping my bones together) every 6 months instead of every 3 months. It seems to be making my teeth a little bit brittle.
The wedding, visits, etc. were great. We're not in the habit of enumerating friends, so it was kind of a surprise to me just how effortlessly we filled up every available minute of the week with great friends, while still sadly failing to see many others. We'll have to come back again soon.
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