Probably Good News

After 48 cycles on the sweet little pill called pomalidomide, my cancer markers are about the same as last month. IgG is higher than I would like to see it, at 1280 mg/dL, but it didn’t jump up again, it actually dropped slightly. M-spike stayed still at 1.1 g/dL. So the cancer still appears to be stable. Dr. LH did mention that stress (3 marathons in 3 weeks?) could contribute to increased IgG, and I know that I have a tooth that is starting to go bad, so those are reasons why IgG might be a little higher than expected.

Lambda light chains dropped a bit, too, while kappa light chains remained the same. I’m not sure that means anything, except it can’t be bad.

Calcium has bounced around in recent months, and it’s back up again. We discussed doing a skeletal survey, to check for bone lesions, but Dr. LH said that if the calcium is coming from bone lesions, it isn’t likely to go down again next month. So we’ll hold off for a month and see. She suggested that better hydration might improve the calcium numbers, and I think she’s right – I know that I don’t drink enough water. I need to figure out some easy way to fit proper hydration into my life so that it happens automatically. Yeah.

I haven’t been blogging here much lately, because we three have been on the road a lot, but we’re going to the ASH Conference in December and I hope to blog several times while there.

Some Current Test Results:

Test

Boring Mayo Clinic Visit

Never. Even though nothing changed this month, I never feel complacent. Forty cycles on the pomalidomide (CC-4047) study are complete, and nothing changed this month, so I could have felt complacent. But I dread the inevitable day that the myeloma figures out how sidestep the pomalidomide – life will change when that happens, maybe not for the worse, there are other treatments, but life will change. Also, I suppose I don’t want myeloma’s reemergence to be a shock when it happens, and it can’t be a shock if I’m always fully aware of the possibility.

Dr RH:

This visit was as routine as any we have. We don’t know Dr RH very well, so after the medical stuff was done we chatted a bit, learned a little about each other. We like him – he’ll do well for us, replacing Dr KDS, who really is gone now and whom we will miss. We also saw Dr L for a few minutes, a treat.

The Evolution of a Myeloma Recurrence:

With few exceptions, myeloma figures out how to defeat every medication. Maybe now, maybe later, even much later, but it does. I am definitely not a doctor or a biologist or anything of the sort, but I nevertheless have a simpleminded theory about that:
Some carcinogen alters the DNA of a plasma cell, or maybe a memory B cell, in such a way that the cell forgets how to die when it ought to, and perhaps with other DNA problems too, but without alerting the body’s normal defenses. There may actually be MANY alterations of the cells, but most are detected and squashed, or cause that cell to die, or fail for some other reason, until one suceeds. This is how cancer starts, including myeloma.
That cell also has the ability to replicate itself or to produce other myeloma cells. I think there is still some dispute about how this happens – is the original progenitor a stem-like cell or an actual plasma cell? Anyway it multiplies.
A medicine (Revlimid, Velcade, melphalan, whatever) is able to kill the myeloma cells or reduce their rate of replication. The tumor burden goes down – yay!
But additional carcinogens, or the same carcinogenic influences, continue to make random alterations to the DNA of the remaining myeloma cells, which mat not be very stable to begin with. Most of these changes don’t make any difference, or they may even cause the cell to die, but eventually one of those changes, by chance, makes a cell resistant to the current medications.
Now, that twice-altered cell is the strongest of the myeloma cells and is able to proliferate faster than the old ones in the face of the medication. It multiplies, replaces the old myeloma cells, and the drug is no good any more.
Anyway that’s my theory and I’m sticking to it. If it were true, what would be the implications? Most important, REMOVE AS MANY CARCINOGENIC INFLUENCES AS POSSIBLE! We should do exactly the same things that we should be doing to PREVENT cancer in the first place:
Eat the healthiest foods, organic where that is important, to reduce the intake of pesticides.
Maintain a healthy weight – studies show that overweight alone is a carcinogen.
Exercise several times per week, to keep the body’s immune system and other systems healthy.
Don’t smoke, duh.
Stay away or protect ourselves from other common carcinogens such as gasoline, solvents, formaldehide in new construction or furniture, herbicides, pesticides, plus food additives such as nitrites and BHA/BHT.
I wrote more about cancer prevention in a previous post. It’s how to live.

Gluten-free oatmeal with organic yogurt, organic strawberries, organic pear, pineapple, kiwi, walnuts. Might be some organic blueberries under there too.

Fighting Secondary Cancers

I’m cheerful today, after visiting Mayo Clinic for the end of the 38th 28-day cycle of pomalidomide. IgG is up a paltry 3%, from 1170 to 1200 mg/dL, but M-spike is down a whopping 17%, from 1.2 to 1.0 g/dL. I don’t actually believe that my monoclonal proteins dropped that much, because last month’s figure was a medical impossibility (higher than IgG), but it feels good anyway. See, it doesn’t take a lot to make me happy. We celebrated with a couple of bowls of kettle-popped organic popcorn.

STABLE is the proper description:

The myeloma is stable. IgG has varied between 923 and 1350 mg/dL since July of 2008, two and a half years. I just want to stay on this regimen forever, running marathons and otherwise enjoying life. It doesn’t work that way, but so far pomalidomide has given me nearly three years of normalcy.

When pomalidomide fails, what’s next for me?

Every treatment fails eventually – that’s a dependable feature of myeloma. Apparently, though, I will have plenty of options. I’ve had thalidomide, pomalidomide, dexamethasone, and low-dose naltrexone so far, no other doctor-prescribed treatments. There are Velcade studies at Mayo right now, and Carfilzomib, plus several new agents which work in magically new ways. Dr KDS mentioned Phase I, II, and III trials – lots going on, and I might be eligible for several of them. I’m feeling good about the future.

We even discussed bone marrow transplant, but I’m not sold on that, for me. I have a slow-moving variety of myeloma, and I’m hopeful that it can be managed by using the existing treatments in a serial fashion and, perhaps, by taking advantage of new ones as they come along. The cure for myeloma is to live long enough to die of something else, and that’s my plan. Meantime, life is to be lived!

What About Secondary Cancers?

There is new evidence that long-term treatment with Revlimid, such as Revlimid maintenance after a transplant, may result in an increased risk of second primary cancers including lymphoma, leukemia, and solid tumors. The risk is still low, perhaps less than 5%, but studies seem to show that it is somewhat increased compared with people not on Revlimid maintenance. Doctors are trying to quantify this risk now, to determine whether it says anything for or against long-term maintenance. The Myeloma Beacon has a very current article on this issue.

So what about pomalidomide? Thalidomide, Revlimid (lenalidomide), and pomalidomide are all immunomodulatory drugs (IMiDs). They all “modulate” the immune system, suppressing it to some extent, in their multi-pronged campaign against monoclonal plasma cells.

THE FOLLOWING ARE THE SUPPOSINGS OF A NON-DOCTOR. READ AT YOUR OWN RISK: We know that an important role of the immune system is to kill cancers before they can get started. The DNA of a cell goes wacko (technical term) for whatever reason, say a coincidental zap from a gamma ray that left the star Alpha Centauri 4.2 years ago, or a treatment by an alkylating agent like melphalan, or a radiation treatment for something, or even a PET scan. The immune system detects the wacko cell and swats it down. Game over.

If the immune system is suppressed, however, maybe it wouldn’t detect the wacko cell, or maybe not until that naughty cell has multiplied and the group has become too strong and adaptable for any immune system to swat it down. Thus the drug doesn’t actually cause the cancer, it simply opens the door for it. Again, this is all supposition; I am not a doctor.

If something like that is happening, though, we might see secondary cancers in people taking other IMiDs like thalidomide, if we look, and eventually perhaps in those of us taking pomalidomide. Dr KDS says that there really is no information on that last point yet. Pomalidomide is too new. I don’t know if anyone has yet looked at the information that does exist. But I do know that I’ve been on pomalidomide for nearly three years now, and that easily qualifies as long-term treatment. There was no transplant, but this is maintenance nonetheless.

How Do We Fight Secondary Cancers?

Job One, of course, is to discuss this with our doctors, and keep ourselves up to date.

Job Two, in my opinion, is to live a healthful lifestyle that fights cancer. That is a huge subject covering nutrition, exercise, sleep, addictions, and much more. It is, however, more or less in our own control. We can influence our own futures and make it more likely that we’ll be here for our grandchildren. I’ve been thinking about writing a book about this (of course there are books out there already), and may blog about it, but here are some simple principles:
Nutrition: We simply avoid eating anything that does not contribute to health. Does soda contribute to health, or a jelly doughnut, or french fries? Of course not! So we choose a healthful alternative, like charged water, a slice of organic whole-grain bread with a little organic raspberry jam, or a banana. Further, we go for the very best foods, especially fruits and vegetables, organic where suggested by the “dirty dozen” lists. Good nutrition contributes in two ways: (1) we avoid ingesting foods that cause cancer, foods full of pesticides, bad fats, and empty sugars; and (2) we do eat high-quality foods containing nutrients that our bodies need to build a competent immune system, including antioxidants and other micronutrients. We are what we eat.
Exercise: Some is good, more is better. A good goal is a half hour, five days a week. We three try for an hour and usually make it. A balanced program, aimed at improving overall health, will include some resistance training (muscle building) and some aerobic exercise, with the prior advice of a doctor of course.
Sleep: How can our health be at its best if we shortchange ourselves on sleep? Studies show that most people need eight hours, some more and some a little less. One test: if I need to use an alarm clock to wake up, then perhaps I’m not getting enough.
Addictions:
Smoking: Oh, for God’s sake, if you still smoke, do whatever it takes to stop. No excuses – it’s killing you and everyone around you. Rehab if necessary. If you live with a smoker, move out.
Overweight: Overwhelming evidence points to overweight as a serious cancer risk. If you are obese (BMI 30+), or even overweight, please find a way back into your bathing suit, whatever it takes. This will require a serious lifestyle change – you will fail if you think it might not. Talk to people who have done it.

We three have followed these principles for years now. Does that mean we won’t get additional cancers? No, it means that our risk is lower than it would be otherwise. That’s all that any of us can do.

Some Current Test Results:

Test

Whoopee!

IgG and M-spike both dropped 17% in the last 28 days, more than offsetting the increase of last month, and returning to levels that are typical of the stable plateau of the last two and a half years or so. Still on the pomalidomide (CC-4047) trial, I’m a happy camper. Please enjoy a beer for me.

Why did it go down? The better question is, why did it go up last month? Maybe because at that time I was recovering from two different virus infections and probably a related bacterial infection, and also had quite recently received my flu shot, the Magnum Jolt version for seniors.

Interesting: If it’s true that IgG went up last month because of challenges to the immune system, then M-spike must have gone up for the same reason. Indeed, it’s possible that the entire increase in IgG came from the M-spike component of IgG. Why would M-spike respond to challenges from intruding organisms? The answer is way above my pay grade.

Neutrophils: Again I had the CBC done at the local clinic on the afternoon before the visit to Mayo, because my neutrophil count seems to be much higher in the afternoon than in the morning. Also, just before the blood draw, I run up four flights of stairs and do some pushups, trying to squeeze out a little adrenaline, which is thought to tease the neutrophils out of their hiding places. Absolute neutrophil count was 2.5 K/uL, well into the normal range and WAY above the cutoff threshold of 1.0. Yay.

Discussed with Dr KDS:
We agreed that I’m still stable on pomalidomide as a single agent. I won’t change anything.

A recent study has (finally!) shown that Zometa, one of the bone-building bisphosphonates, actually has a modest anti-myeloma benefit in addition to its bone-strengthening ability, improving both the average time to disease progression and the overall survival of study participants. Doctors are still getting their heads around this, but one possibility for some patients is Zometa once every month! Zometa can have serious side effects, though, including unusual and disabling fractures, and osteonecrosis of the jaw, so it is not an automatic prescription.

Two more studies, evaluating the use of Revlimid as maintenance therapy after stem cell transplant, showed that patients in the Revlimid arm of the study developed more secondary cancers than those in the placebo arm. Numbers were small, however, with less than 3% in both arms together developing a secondary cancer. Both studies, by the way, also demonstrated that maintenance therapy improved time to disease progression, but neither showed a clear improvement in overall survival.

Recent evidence suggests that my immune system may not be as strong as I have though it was. Three different virus infections were defeated only very slowly. Dr KDS is concerned that I could contract an opportunistic fungal infection called pneumocystis pneumonia, common with AIDS patients who may also have compromised immune systems. She prescribed a sulfa-based antibiotic called trimethoprim-sulphamethoxazole, brand name Bactrim, to be taken every day as a prophylactic treatment to prevent that pneumonia and any number of other bacterial and fungal infections.

There is a slim possibility of myelosuppression, however, which means low red and white blood counts; HELLO I already have that from the pomalidomide. It can also, rarely, cause liver or kidney failure, a potentially fatal complication. I hadn’t heard of Bactrim prophylaxis before, but Dr KDS said that it has been used without incident by other patients in my situation. She knows that I will study this stuff and do my best to balance the risk of pneumonia against the risk of side effects, before making a decision. She also gave me an order for liver and kidney function tests which I can have done after trying the antibiotic for a week or two. Perhaps I’ll talk to Dr B, my new PCP, about this.

Some Current Test Results:

Test

Uncertain Result

At the end of the 35th cycle of pomalidomide, IgG is up 15% to 1300 mg/dL, and M-spike is up 9% to 1.3 g/dL from the end of the previous cycle. Further, lambda light chains are up a little with kappa chains down. The markers are consistent, all pointing to an increase in actual tumor burden.

But maybe not. I had a bad cold with fever for most of the four weeks preceding this blood draw, and then also got my “high dose” flu shot. Either of those insults could have caused IgG to go up, the “good” immunoglobulins responding to the threats. Also, M-spike had been at 1.3 two months before, so it’s just back to where it had been. As always, I’ll be wondering what next month’s tests will bring.

Neutrophils were up this time, well into the normal range, probably in response to those same two threats. We get the CBC at the local Stillwater clinic the afternoon before the Mayo Clinic visit, because my neutrophils are much higher in the afternoon, but I suspect they would also have been well above the threshhold of 1.0 K/uL in the morning at Mayo on this occasion.

Calcium is up because I took my usual supplements. Often I skip calcium tablets for a day or two before the Mayo blood draw, to avoid this slightly-high reading. It will be down next month, if I remember to skip calcium.

Flu Shot:

I got mine at the local clinic, and learned afterward that there are two dosages: (1) Normal dose for adults, and (2) “High dose” for seniors 65 and older, four times the strength, which is the shot I received. In discussing this later at Mayo Clinic, it appears that the CDC has given very little guidance about the use of this high-dose shot. Should a senior be given that shot even if he/she has a compromised immune system? If so, what about an adult under 65 with a compromised immune system? Apparently, doctors are left to make this decision themselves with no help from the CDC.

Some Current Test Results:

Test

Pomalidomide Rocks

At least for me it does. I’ve been on a study of Celgene’s pomalidomide (CC-4047) for 34 complete cycles now, and it has kept my myeloma stable for all of that time. At first I took it with “low-dose” dexamethasone (DEX), and after two years graduated to pomalidomide alone (actually with aspirin and acyclovir). M-spike and IgG dropped quickly in the first three months, and for more than two years IgG has been about a third of the starting value with M-spike tracking appropriately.

“Pomalidomide” is the drug’s generic name, while CC-4047 is a code name for the same drug in drug trials. Someday it may have the brand name “Actimid,” when it is available for sale. I hope that happens soon, because it’s good stuff and people are dying right and left.

I think this is publishable news: Mayo Clinic will soon open a new arm of the CC-4047 study. Entrance criteria were not established when I was there on Oct 20, but one objective is to make it available to more people who need it, so I suspect the entrance criteria will be fairly wide.

Cycle 34 Test Results:

At the end of the previous cycle, my IgG was down a little and M-spike was up. This time, IgG is up a little and M-Spike is back down. I suppose that’s the definition of “stable” for us myelomiacs, because these tests do have some error tolerance and our blood varies too. Other markers, like lambda light chains, calcium, and some of the CBC blood counts are virtually unchanged. No problem – a boring visit -:) Let’s have lots more of those!

Neutrophils were a bit of a surprise, though. The study requires at least 1000 of those tiny critters per microliter of blood, or else the pomalidomide has to be stopped until neutrophils climb above that mark again. Sometimes mine have been below 1000, so we’ve chosen to switch to 1:00 pm blood draws, taken the day before the Mayo visit, because my neutrophil counts are reliably higher in the afternoon. This time, though, the afternoon count was 2100, actually well into the “normal” range, and another count the next morning at Mayo also showed 2100. Why? Maybe because I have a miserable cold, and those little buggers are an essential part of the battle that’s going on. They have been recruited and they are rallying!

Mayo, Dr KDS:
I have a pain in the index finger of the left hand – can’t quite localize it though. Could it be myeloma? Answer: Probably not – myeloma usually attacks larger targets with more marrow.
I changed my diet this month to reduce the amount of simple sugar. This means no cookies or other sweets, and less fruit. Since the myeloma didn’t change much, I believe this experiment was a failure and will go back to the higher-fruit diet.
I also had more constipation than usual this month. It’s a known side effect of pomalidomide, but we agreed that the increase was probably due to the reduction of fruit in the diet.
An afternoon blood draw produces a neutrophil count about 50% higher than does a morning draw, for me. Dr KDS tried that with another patient, though, and it didn’t work. We’re all different.

Some Current Test Results:

Test

US 52 Was Under Water

We three drive down US 52 from the east side of St Paul to Rochester once every 28 days for my checkup at Mayo Clinic. It’s the shortest, fastest route. Usually we get up at 3:50 am, take an hour to shower and get ready, then 90 uneventful minutes later I’m in line for my 6:30 am blood draw. We knew that Thursday would be different, because of the heavy rain, but we didn’t know how different. A check of MNDOT’s Traffic Conditions Website showed that US 52 was closed, so we went another way – no fun driving in “driving” rain, but US 61 & 63 were open and it took us only about a half hour longer. Heading back, that MNDOT web site said that US 52 was open again, so we started out that way. Just a few miles south of Pine Island, though, we found water rushing across the four-lane highway. Some vehicles were crossing it, but some were not and we turned around. Police were conspicuously absent. At 5 pm the local news said that US 52 was closed right where we encountered the water.

We later discovered that the city of Pine Island had in fact become an island, though it normally is not.

IgG versus M-Spike:

IgG is a measure of ALL Immunoglobulin G proteins, good and bad, where M-Spike is a measure of just those Immunoglobulin G proteins that are monoclonal, the bad ones, all exactly the same. Medically, M-Spike can never be higher than IgG. Thursday my IgG was 1070 mg/dL, but M-Spike was 1200 mg/dL (1.2 g/dL). Not possible. I hate that! I was feeling pretty good about another “stable” result until that M-Spike came bombing in.

I asked Dr KDS about this impossibility – which number is most likely to be wrong? She wasn’t sure, but assured me (paraphrasing here) that she has seen this before, because both tests have an error tolerance, but that she was NOT worried. Further, I’m still stable and, as always, let’s see what next month brings.

Sigh. I fret about this stuff, and was hoping for a fret-free 28 days. I’ve been on the pomalidomide (CC-4047) study for 33 complete cycles now, and it has done a fine job of keeping me stable. Nevertheless, I know that the ride will end some day and I will need to take a different course of drugs that may have much worse side effects. So I’m always wondering if that time is near and hoping that it isn’t.

For now, though, I’m going to try to convince myself that the M-Spike number is wrong. There is nothing in the other cancer markers to suggest an increase in tumor burden. Calcium is fine, kidneys are fine, liver is fine, and light chains are not much changed. In fact, an IgG measurement of 1070 mg/dL is actually a decrease of 3% from August and 8% from July. We’ll go with that.

Carfilzomib:

Mayo Clinic will soon start a trial of this brand-new drug. Carfilzomib is a proteasome inhibitor, like Velcade, at least as effective but much less likely to cause painful neuropathy. Furthermore, it can be effective in patients for whom Velcade has failed. I blogged about it here. I’m not sure what it will take to qualify for the trial, but if you go to Mayo you might ask about it.

Velcade:

I am not a medical doctor, so you shouldn’t believe anything that I say. Nevertheless: If you are offered twice-weekly Velcade as a treatment, just say NO. Twice-weekly infusion is still the official, approved regimen, even though several studies have shown that once-weekly infusion is much less likely to cause painful neuropathy in most patients. In addition, there can be a threshhold effect: if a patient on twice-weekly infusions does develop neuropathy, switching to once-weekly may not help the neuropathy much. Once you get the neuropathy it’s yours to keep, and any amount of Velcade will reactivate it. A patient who starts out with once-weekly infusions, however, is much less likely to develop serious neuropathy in the first place. If your doctor insists on starting out with the official twice-weekly protocol, change doctors. No kidding. Velcade is an excellent drug, but it’s useless if the neuropathy prevents you from taking it.

Some current test results:

Test

Neutrophils and Dermatology

On Thursday, July 29, I visited Mayo Clinic to assess Cycle 31 of pomalidomide (CC-4047). Still stable. IgG was up about 3.5%, and M-spike went from 1.0 to 1.1 g/dL. But we’ve been here before. In February, IgG was a little bit higher than it was Thursday, and M-spike was 1.1 just last May. The numbers may have a slight upward trend, but they do seem to bounce around on their way up. I’ll not worry this time. Maybe next time.

Neutrophils:

My neutrophil count was 930 cells per microliter, just below the threshhold. They won’t give me a new bottle of 28 pomalidomide capsules for the next cycle until neutrophils go above 1000.

Therefore, we scheduled another CBC (with differential) for the afternoon, because my neutrophil count seems to follows a circadian rhythm, rising through the morning into the afternoon. In all but one of the previous four cycles I have needed a second CBC, and in each case the second neutrophil count was comfortably above 1000. In all of those cases the second count was taken on a later day, in the afternoon.

This time, though, the second count was done the same day, in the same Mayo Clinic lab. By Thursday afternoon, neutrophils had jumped 63%, from 930 at 9:00 am to 1520 at 1:00 pm. Furthermore, the total white cell count also jumped up from its all-time low of 2.8 up to 3.8.

I knew that physical exertion could increase neutrophils, so before the 9:00 am blood draw I jogged a half mile, walked up and down six flights of stairs, and did 30 pushups. If that helped, it wasn’t enough. Dr Lacy informed me, though, that it’s really adrenaline that flushes the neutrophils into the blood stream. I asked if a good scare would do as well as exercise, and she thought it would. Anyway, for the second blood draw, I ran a few very short, high-intensity sprints and ran full speed up two flights of stairs. I really don’t know if that helped either – maybe the increase is all due to normal circadian rhythm.

Next time, I’ll get the CBC drawn the afternoon of the DAY BEFORE the Mayo Clinic visit, at a local clinic. This is OK with Dr L, and may solve the problem of unnecessary duplicate neutrophil counts.

Dermatology:

At the last visit, I asked Dr L about a bump on my forehead, wondering if it was any kind of skin cancer. She didn’t think so, but scheduled a “dermatology consult” for this visit. Well, at Mayo Clinic that’s more than a cursory peek at one spot. I was asked to put on a hospital gown (the kind that opens in the back, of course), and the doctor checked most of my skin, even those parts that are almost always in the shade.

He was not at all interested in the little forehead patch that brought me in, but he saw several “pre-cancerous” spots on my forehead and zapped them very quickly and efficiently with a little can of freezing spray. He said that about one in a hundred of those spots can become malignant. He asked about a spot on a knuckle, and I told him that it was a bruise (I knew when it happened), but he nonetheless zapped that one too.

I asked him about the skin on my arms, which is now so thin and weak that I can’t even use band-aids on it. I know that it has been thinned by age and by steroids, but he said the big culprit is sun damage. We discussed sun screen (use a good one, such as the Vanicream that Mayo Store sells), and hours of the day – he suggested 10:00 to 3:00 I think, but I would go another hour in the afternoon, 10:00 am to 4:00 pm, daylight savings time. That’s a three-hour window each side of high noon, sun time.

We asked if there was a way to repair the damaged skin. He said that Retin-A has been tried by some, but he wasn’t impressed by the result. Retin-A can make skin even MORE sensitive to the sun, and has other significant side effects, so I’ll stay away from it but probably will be more careful to use sunscreen.

The doctor said that if any of the frozen spots became open sores, I should just use vaseline on them. We asked about Neosporin, because I’ve had such excellent results treating other cuts and scrapes. He replied that they recommended Neosporin in the past, but eventually discovered that about a third of people are allergic to it. So far no problem with my treated spots, but if there is a problem I’ll use Neosporin anyway because I don’t seem to be allergic.

Some current test results:

Test