Even Better News, Probably

Mayo Clinic Visit Wednesday, April 30, 2009, end of Cycle 15:

Results:

CC-4047 is an analog of thalidomide and Revlimid, presumably an advancement on both. One little-advertised feature of Revlimid is that a patient's M-spike may decline in two phases. The first phase may take the spike down to a plateau, and if there is a second phase it may produce another gradual decline to even lower numbers, possibly much lower. Dr L has a theory that the first phase may be the Revlimid actually killing the naughty plasma cells, as we might expect, and the second may happen because the Revlimid has helped the immune system itself to fight the myeloma.

The good news for me, perhaps, is that CC-4047 seems to show the same two-phase response for some patients, maybe including me. The CC-4047 study is less than a year and a half old, so information is still somewhat tentative. My own M-spike initially dropped rather quickly from 2.7 to 1.1 g/dL, then to 0.9 and back up to 1.1. In the past four cycles, though, it has gradually dropped again, from 1.1 down to 0.8 g/dL, the lowest level we have seen in the fifteen 28-day cycles that I have been on the study. I can only hope that this is the beginning of the second gradual downward movement.

IgG stayed the same, at 1060 mg/dL, suggesting that the drop in M-spike might be illusory. M-spike is known to be a relatively inaccurate measurement, and indeed the the printout says "no significant change since the last measurement," even though it dropped from 0.9 to 0.8 g/dL. However, since January the drop is from 1.1 to 0.8, enough to be significant. The trend is certainly down, not up.

The only iffy test results are the white blood cell and neutrophil counts, both of which took a bit of a dip this month. CC-4047 can cause those counts to tank, which is not good. But they bounce around a bit and have been low before, so we'll see next month. We live month to month, and I'll take this one!

Related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Feb 05		Mar 04		Apr 02		Apr 30		Remarks
M-spike g/dL		1.0		0.9		0.9		0.8		Best tumor measure
IgG mg/dL		1160		923		1060		1060		Variation is normal
L FLC mg/dL		2.78		2.64		3.04		2.55		Free light chains
Calcium mg/dL		9.7		9.7		9.5		9.6		Below 10.2 is best
Creat mg/dL		1.0		1.0		1.0		0.9		Kidney, lower is better
HGB g/dL		14.9		13.7		14.7		14.3		Hemoglobin, normal
RBC M/uL		4.28		3.89		4.26		4.01		Red cell count, low
WBC K/uL		5.0		4.5		4.2		3.6		White cells, normal

Doctor:

Sunshine and I discussed a few other things with Dr L:

• It seems as if the dexamethasone (DEX) had aged me five or ten years in the last year, noting especially the thinning skin and wasting muscle. Dr L was not surprised.
• It also seems like there are two DEX days now, not just one. The DEX effect seems to last longer. Again she was not surprised.
• She had mentioned in an earlier visit that the body does become more sensitive to the DEX as time passes. This time she said that this unfortunately applies only to the side effects and not to the efficacy of the drug.
• When I asked about the effect of the drugs on the thyroid, she mentioned that the IMiD drugs (thalidomide, Revlimid, and probably CC-4047) can sometimes inflame the thyroid, and in the worst case can cause the thyroid to "burn out," eventually resulting in hypothyroidism. This is why the CC-4047 study protocol calls for a TSH test every three cycles, which is frequent enough to catch the problem. My TSH was 2.0 mIU/L, which is fine.
• We discussed a reduction in the DEX dosage, from 8 mg to 4 mg once weekly, but because of the good M-spike result we decided to change nothing. I love life more than I hate DEX.
• I have eaten one grapefruit every day since about January, which is roughly when this M-spike decline began. Coincidence? She was not certain whether grapefruit would have an effect on the strength or efficacy of either the DEX or the CC-4047. But I'm not inclined to change that either.
• Don's basic rule of life: "If it works, YOU CAN'T FIX IT." Corrolary: "So don't try."
• We had quite a discussion about the shingles vaccine. It is a "live" vaccine, so there is a theoretical possibility that it could actually cause a case of chicken pox in an adult with a compromised immune system. That could be horrible and maybe even fatal, so oncologists simply don't give that vaccine to people with myeloma and there is almost no clinical information on whether myeloma patients would actually develop chicken pox from the vaccine.
• My primary care physician, Dr PCP, had suggested the vaccine and he's a very smart man, so I'm still thinking about it. As far as I know, my immune system is as competent as it has ever been. If it's safe for normal adults, it should be safe for me. Shingles is pretty nasty too.
• In February the electrocardiogram (ECG) report said "Ventricular escape beat followed by SVPC." I'm not even sure what that means - I hope it was just because I have a runner's heart and I was on a lot of caffeine that day. Anyway it wasn't there this time.
• But this time the report says "minimal voltage criteria for LVH, may be normal variant." This same statement appeared once before too, about a year ago. I think it's the measure of the height of the major voltage spike on the ECG. Dr L said that the voltage can show higher on lean people (like runners), and I also think it has to be higher for a person with a very low heart rate, because the heart has to pump harder on each beat. A normal heart rate is 60 or so, but mine was 40 for that ECG - normal for me because I'm a runner. I'll ask Dr PCP about this.
• We talked briefly about new drugs. She mentioned a drug called Zevalin, a monoclonal antibody with the capacity to kill the progenitor cells ("stem cells"), perhaps to be used in combination with melphalan which kills the mature myeloma cells. Apparently someone at Mayo is doing work on this. If this were successful, we might actually be headed for a cure. Yikes.
• The CC-4047 study has been reopened more than once now for a modest number of additional patients. The last opening, now filled, was for people for whom Revlimid has failed. This time it is for people for whom both Revlimid and Velcade have failed. Apparently the FDA does not want to approve another new drug unless it shows a significant advantage over drugs already available. If CC-4047 works for those hard-to-treat patients, it will certainly show that.
• I asked if the muscle wasting caused by DEX would affect my heart as much as it affects leg muscle. She thought not, because the heart is "smooth" muscle, different from motor muscles.

Three days before the Mayo visit I saw Dr PCP with a lits of questions about DEX and a few other things:

• I asked if there was a way to minimize the muscle-wasting effect of DEX by timing my running and other exercise properly. Is it best to exercise on DEX day, or is it best on the day before or the day after? He didn't know, but will look into it. Good guy.
• He mentioned that immunizations, such as the flu shot, are rendered less effective by DEX, which suppresses the immune system and thereby its response to the vaccine. He thought perhaps the best timing for that would be two days after taking the DEX.
• The reason that DEX is used for us instead of prednisone is that there is less problem withdrawing from DEX, so it's better in applications where the corticosteroid should be pulsed instead of continuous.
• He knows of no way to toughen thin skin. Tsk.

The end. For now.



Dinner: Wild-caught Alaskan sockeye salmon (canned) with organic yogurt and a little cheese, toasted slivered almonds, organic green peas, organic strawberries. Life is good.

Good News Again

Mayo Clinic Visit Wednesday, April 2, 2009, end of Cycle 14:

Results:

M-Spike is the same at 0.9 g/dL, IgG is up slightly from 923 to 1060 mg/dL, and Lambda light chains are also up a little from 2.64 to 3.04 mg/dL. I'm not concerned about IgG & light chains, because those numbers do seem to fluctuate a bit from one cycle to the next, as does the M-Spike for that matter. Taking the long view, these major markers have been level or down since June, 2008, and the trend is pretty much level. This is great, and Hooray for modern science!

CC-4047 is an experimental drug, an analog of Thalidomide and Revlimid but apparently more potent and with fewer side effects. In early March, a year ago, I started on the Mayo trial of CC-4047 with dexamethasone (DEX). By June, M-Spike dropped dramatically from 2.7 down to 1.1 g/dL. From there it dropped to 0.9, then up again to 1.1, and back down. Those variations may not have any meaning, and in fact they may be within the measurement error of the tests. Eventually the treatment will probably fail, as they tend to do, only time will tell. Meantime, there is life to be lived.

Related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Jan 08		Feb 05		Mar 04		Apr 02		Remarks
M-spike g/dL		1.1		1.0		0.9		0.9		Best tumor measure
IgG mg/dL		1350		1160		923		1060		Variation is normal
L FLC mg/dL		3.31		2.78		2.64		3.04		Free light chains
Calcium mg/dL		9.9		9.7		9.7		9.5		Below 10.2 is best
Creat mg/dL		1.1		1.0		1.0		1.0		Kidney, lower is better
HGB g/dL		15.3		14.9		13.7		14.7		Hemoglobin, normal
RBC M/uL		4.36		4.28		3.89		4.26		Red cell count, low
WBC K/uL		4.6		5.0		4.5		4.2		White cells, normal

Doctor:

I met again with the nurse-practitioner Dr KDS, but our discussions were short this time. She did give me a prescription for physical therapy designed to strenthen the bones that were known to be threatened by myeloma lesions a year ago. I have previously discussed this with a personal trainer and had one session with her, but will now make an appointment with a physical therapist. Perhaps I'll learn a set of exercises that I will actually do on a regular basis.



Hormone- and antibiotic-free lamb, organic broccoli with shredded parmesan cheese, onion, Rose's lime jelly.

Better Than Plateau

Mayo Clinic Visit Wednesday, March 4, 2009, end of Cycle 13:

Great News!

A month ago, at the end of Cycle 12, M-Spike went down from 1.1 g/dL to 1.0 This month it went down again, to 0.9 g/dL, for a total drop over two cycles of 18%. Further, in that two-month period, IgG dropped from 1350 to 923, a total drop of 32%and the lowest IgG ever, suggesting that the M-Spike drop is not only genuine but perhaps even understated. Celebration is in order.

CC-4047 is an experimental drug by Celgene, an analog of Thalidomide and Revlimid but hopefully more potent and with fewer side effects. Exactly a year ago I started on the Mayo trial of the drug combination CC-4047 with dexamethasone (DEX). M-Spike dropped dramatically from 2.7 g/dL down to a low of 0.9 g/dL last October, the best value in more than four years, then climbed back up to 1.1. Now in two 28-day cycles it has retreated again to 0.9.

So after it went up again, why did it go back down? What is different? Is it something that I did? If so, what can I do, with the help of Sunshine and Sweet Pea, to keep M-Spike going right on down? Here are a few possibilities:

• In Cycle 13 I had a perfect record of taking my supplements, twice a day. Never missed once. Maybe they actually do help? The only problem with this theory is that I wasn't nearly as consistent in the previous cycle, number 12, when M-Spike also went down.
• For this Cycle 13, I added three new items to the list of supplements:
  • Genistein, a soy isoflavone which is reputed to have some anti-myeloma benefits, see for example Margaret's Corner;
  • Spectra 303, a thyroid supplement; and
  • Thyroid Energy by Now, another thyroid supplement.
  • I'm thinking that if anything helped M-Spike it was the genistein, though the thyroid marker TSH did improve too and who knows if a healthier thyroid could benefit M-Spike. Neither would explain why Cycle 12 also showed improvement.
• During Cycle 13 I ate more grapefruit than I had been eating. Grapefruit is known to enhance the effect of some drugs by interfering with the normal action of digestive enzymes. Usually I ate the grapefruit in the evening, an hour or two before taking the CC-4047, and it's certainly possible that this resulted in more CC-4047 in the blood. But again, it doesn't explain why Cycle 12 also showed improvement.
• In the past two months Sunshine has been cooking with more coconut oil than she ever used before. Every morning I have two eggs cooked in a little pure, organic, non-hydrogenated coconut oil, for example. Popcorn, when we have it, is popped in coconut oil, and other foods are cooked in it as well. Coconut oil is well regarded as a traditional treatment for shingles and other forms of the herpes virus, but I haven't heard of it as a treatment for myeloma. Nevertheless it is a change in our lifestyle that occurred at about the beginning of Cycle 12.
• According to Dr L, the side effects of DEX tend to increase as time goes by, which is one reason why a doctor may reduce the dosage. My dosage started at 40 mg once weekly and was gradually reduced, ending up at 8 mg once weekly last November, for Cycle 10, where it has remained. Question: If the side effects of DEX increase with time, does the efficacy increase as well? Dr KDS didn't know, so I will ask Dr L when I next see her.
• For each of the Mayo visits, we travel from the Minneapolis / St Paul area to Rochester, MN. Usually we get up very early and drive about 90 minutes in the dark for a 6:30 am blood draw. I'm not supposed to have any food or drink, except a little water, for 12 hours before the blood draw. However, for the last two visits, and only those two, with the permission of Dr L, I have enjoyed a 16-ounce thermos of black coffee on that drive. Could it be that the coffee is somehow interfering with the tests, and the cancer markers haven't really changed? I don't think so, because M-Spike and IgG have dropped for two cycles in a row, but it's a thought. I'll enjoy my thermos again next month and see what happens.

Other Good News:

Two days before the Mayo appointment I injured my back slightly while doing pushups I think. Or pullups. That's not the good news. Dr KDS and Dr L agreed that I should have another x-ray bone survey, to include that area of the back but also all of the large bones in the body, because:

• A year ago, lesions were found in three bones including a vertebra;
• I'd had no x-rays or bone scans since;
• Myeloma always poses a risk for bone lesions and actual broken bones; and
• I had a symptom that could indicate a problem in a vertebra.

The good news is that the bone survey was negative. No lucent lesions. The injury is minor - I'm sure it will be gone soon.

Related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Dec 11		Jan 08		Feb 05		Mar 04		Remarks
M-spike g/dL		1.0		1.1		1.0		0.9		Best tumor measure
IgG mg/dL		1260		1350		1160		923		Variation is normal
L FLC mg/dL		4.03		3.31		2.78		2.64		Free light chains
Calcium mg/dL		10.1		9.9		9.7		9.7		Below 10.2 is best
Creat mg/dL		1.0		1.1		1.0		1.0		Kidney, lower is better
HGB g/dL		14.6		15.3		14.9		13.7		Hemoglobin, normal
RBC M/uL		4.20		4.36		4.28		3.89		Red cell count, low
WBC K/uL		5.3		4.6		5.0		4.5		White cells, normal

Doctor:

I met again with the nurse-practitioner Dr KDS. Here is some of the discussion:

• My doctors have started ordering the test for LDH at every visit now. My understanding of Dr KDS' explanation is that LDH is a non-specific marker for cell damage and is used as a screen for a variety of problems that might not otherwise be picked up. Mine was normal.
• My M-Spike has declined on the test protocol from 2.7 g/dL to 0.9 g/dL. Tha's called a "partial response (PR)." To get to the next level, "very good partial response (VGPR)," it would have to get down to less than 10% of the initial value, or 0.2 g/dL. Well, I'm going to define my own level, called "good response (GR)," which is less than 40% of the initial value. I'm there.
• Last month my TSH, a thyroid marker, was 5.4, slightly above the reference range. Since then I have been taking some over-the-counter thyroid supplements, and this time TSH was 3.5, somewhat better. I'll keep taking them.
• Anakinra (Kineret) is an existing FDA-approved drug which has shown an ability to inhibit the growth of myeloma. It is currently in an ongoing Phase II trial for patients with smoldering myeloma.
• There are ongoing studies of three- and four-drug combinations which seem to have spectacular results, similar to the results from a stem cell transplant, sometimes even better. But the question is, what happens when the myeloma comes back, and we've already shot the whole quiver of arrows at it? Dr KDS says that there is no clear answer yet, and the issue is hotly debated, but she articulated three possibilities:
  • Do it again, the same combination of drugs or another combination. Maybe it will work; or
  • Try the individual drugs, one or two at a time, likely in greater doses than they were used when in combination; or
  • Perhaps by then a new drug or combination will be available. Time and research are our friends.
• IgG measures all immunoglobulin G, M-Spike measures the monoclonal (bad) part of that, and the difference is good immunoglobulins which can fight infection. For example, the most recent results show IgG = 923 mg/dL, M-Spike = 900 mg/dL (same as 0.9 g/dL), so the difference is 23 mg/dL good stuff. Before I went to Mayo, my tests were done at Minnesota Oncology Hematology PA (MOHPA).
  • For 15 sets of tests at MOHPA, the difference between IgG and M-Spike (good stuff) averaged 690 mg/dL.
  • For the next set of 14 tests, all at Mayo, the difference averaged 212 mg/dL.
  Why such a big discrepancy in "good stuff" between MOHPA and MAYO? I'm pretty sure that it is a discrepancy in laboratories and not an artifact of the CC-4047 treatment, because the "good stuff" at Mayo was only 260 at my very first Mayo visit, before any CC-4047. Mayo reads M-Spike higher than MOHPA does. Of course I have no idea which lab is correct. Dr KDS agreed that such a discrepancy could exist, though it seems like rather a large difference.
• I asked her if there might be a way to kill all memory B cells, or even all B cells, on the assumption that these contain the "stem cells" that cause myeloma to return. Sort of a plasma-cell reboot, but less than a complete stem cell transplant. A new experimental drug called belimumab is a possibility here, but she hadn't heard of it and the whole concept is well over my head.
• We re-discussed last month's ECG report of "ventricular escape beat with SVPC." On the internet it looks kind of scary. But she looked it up on a Mayo data base and found that it is not uncommon in people with otherwise low heart rates. That's me. I won't worry about it - there will be another ECG in a couple of months and I'll arrange to be less-well caffeinated for it.

Leftovers for dinner: Free-range no-hormone no-antibiotic bison, organic chicken, organic lettuce, organic squash with organic salsa, kiwi, avocado.

Green Tea with Velcade

By now you have probably heard the warning ricochetting around the myeloma survivor community about NOT taking green tea or its derivatives with Velcade (bortezomib). It turns out that Green tea polyphenols block the anticancer effects of bortezomib and other boronic acid-based proteasome inhibitors. EGCG was particularly effective at preventing cell death from Velcade, both in vitro and in real people.

So, if we're on Velcade or the trial drug carfilzomib, we should stay away from green tea, right? And what about black tea, which contains similar polyphenols? Just don't drink tea?

When I brought this to the attention of my naturopath, Dr HH, she immediately took it a step further and wrote to an author of the study published in Blood Journal (see link above), asking if there was a safe time period before and after a Velcade infusion for a person to enjoy a cup of tea. The author responded by email as follows: "Based on our observations, in combination with the known half lives of bortezomib and green tea products, we would recommend a "safety zone" of 24 hours before and 24 hours after bortezomib injection for the avoidance of green tea and green tea products."

So it appears that you can enjoy your cup of tea and maybe even your EGCG supplement, if you like, as long as you maintain that 24-hour "safety zone" of time.

Questions remain: Would green tea interfere with any other myeloma drugs? Would other supplements interfere with Velcade? We have plenty of studies showing the benefits of various supplements, but few those have the supplement in combination with FDA-approved medicines like Revlimid, Thalidomide, or even dexamethasone.

Plateau Continued

Mayo Clinic Visit Thursday, February 5, 2009, Cycle 12:

Good News!

M-Spike went down from 1.1 to 1.0 g/dL and IgG from 1350 to 1160 mg/dL. Together, these results seem to indicate an actual drop in tumor burden of perhaps 10% or so. Maybe not, because test results can vary, but most likely the cancer is down. We celebrated last night.

I do wonder WHY it's down, though. I'm still taking CC-4047 2 mg daily and dexamethasone (DEX) 8 mg once weekly. What else was different in this last month? Or was it the previous month that was different, when it seemed to go up? I dunno. Anyway we'll take it! Thanks to Celgene for CC-4047, Mayo Clinic for excellence in medicine, and specifically to Doctors L and KDS.

Other test results were mostly good too, and in fact mostly unchanged. Light chains are down a little, but the ratio is basically unchanged. White counts and hemoglobin are within the reference range for "normal" people. Red cell count is at the bottom edge of the range, where it always is. I do have three little things to whine about, but I'll put those last because they don't seem very important.

Related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Nov 13		Dec 11		Jan 08		Feb 05		Remarks
M-spike g/dL		1.0		1.0		1.1		1.0		Best tumor measure
IgG mg/dL		1170		1260		1350		1160		Variation is normal
L FLC mg/dL		3.25		4.03		3.31		2.78		Free light chains
Calcium mg/dL		9.8		10.1		9.9		9.7		Below 10.2 is best
Creat mg/dL		0.9		1.0		1.1		1.0		Kidney, lower is better
HGB g/dL		14.6		14.6		15.3		14.9		Hemoglobin, normal
RBC M/uL		4.19		4.20		4.36		4.28		Red cell count, low
WBC K/uL		4.3		5.3		4.6		5.0		White cells, normal

Doctor:

I met again with the nurse-practitioner Dr KDS. Here is some of the discussion:

• In connection with my "plateau," Dr KDS mentioned the concept of managing myeloma as a chronic disease rather than a fatal one. But we both know that it's too soon to say that - people are still dying every day.
• I asked Dr KDS about the effect of DEX on the thyroid. She wasn't aware of any effect.
• In a recent visit, my naturopath raised the subject of chronotherapy, also called chrono-modulated therapy, in which the chemo is administered at the time of day that takes advantage of a person's biorhythms to maximize the benefit and minimize the side effects of the drug. Dr KDS thought that it doesn't much matter for the CC-4047. She said that the effect of the DEX peaks 8 to 14 hours after it is taken, so a person should determine for him/herself when s/he wants that to happen. Most people like to take it in the evening, so that the effect is maximized during the following day.
• Since both CC-4047 and DEX have a half-life in the body of eight hours or less, I think (based upon my extensive medical knowledge - Ha ha) that there IS likely a time of day when each of those would be most effective. I wonder when that is.
• We have no Phase II data on length of the plateau for CC-4047, so I asked about Revlimid, a similar drug, in comparison with thalidomide. She made a call and reported that the median "time to progression" for Revlimid is about 30 months, much more than thalidomide. Some people are at 50 cycles and still going on Revlimid. We can hope that CC-4047 gives a plateau of that quality.
• I asked about the targeted measles therapy project, and she said that it is currently in a second Phase I trial with real patients.
• Dr L had said that people get more sensitive to DEX as time goes by. I asked if that applied to the benefits of DEX, or only the side effects. Dr KDS wasn't sure.
• The next visit will be almost exactly one year from my first tests at Mayo. I asked if there is any set of tests that are done on an annual basis, such as skeletal survey, bone density measurement, or PET scan. She said not unless there is a symptom that suggests a need for the test.
• See, the problem is that people cruise along thinking they are on a plateau and suddenly a bone breaks. Yikes. That has happened to many of the people in my local support group. If it happened to me, almost any broken bone would stop my running, so my lifestyle would change instantly and dramatically. For anyone, including me, shouldn't we find a way to spot a weak bone and treat more aggressively before a break occurs?

Whining:

• As part of the study protocol, Mayo does an electrocardiogram every three cycles, and did one Thursday. The doctor always reports "bradycardia," a slow heart rate, which we know about. Runners have strong heart muscles and low heart rates. This time, though, we also got this report: "Ventricular escape beat and SVPC are now present." I don't know what that means, and it doesn't sound good, but Dr KDS wasn't worried about it. I suspect that it was due to being overcaffeinated for the ECG. Dr KDS didn't disagree. Coffee AFTER the ECG next time.
• My TSH (thyroid marker) was 5.4, just above the reference range of 0.3 to 5.0, suggesting that I may be hypothyroid. Hmmm. They do this test every three months too, and it has bounced around a bit in the past year. I will self-treat for this in the next three months, using supplements recommended by my naturopath, and we will see if it drops. I'd prefer it to be down around 2.0.
• After my run Thursday my right foot felt like it was waking from being "asleep," a bit prickly and cool. This lasted for several hours, and could be the beginning of peripheral neuropathy, which can be caused by drugs like CC-4047. I have felt this before when I was taking thalidomide, a similar drug. In all cases it was triggered by running and it disappeared in a few hours. We'll see - if it's peripheral neuropathy it will be back.

M-Spike Versus IgG (or IgA):

M-Spike (Spike) and IgG both measure immunoglobulin G, which is one of the proteins that our bodies make to fight off infection. Spike measures the useless, monoclonal immunoglobulin made by the malignant plasma cells, whereas IgG measures BOTH the useless monoclonal immunoglobulin and the GOOD useful immunoglobulins that fight infection, made by the normal plasma cells. In United States labs, Spike is usually expressed in grams per deciliter (g/dL), whereas IgG is expressed in milligrams per deciliter (mg/dL). We can put them in the same units, mg/dL, by multiplying Spike by 1000. Example from Thursday's results: Spike is 1.0 g/dL, which is the same as 1000 mg/dL. Subtracting that from the IgG of 1160 mg/dL, we see that the GOOD immunoglobulins (IgG - Spike) are 160 mg/dL. Note that IgG must always be greater than Spike, or something is wrong. It can be quite a lot greater if the body has recently fought an infection. The measurement of IgG is more accurate than Spike, but is harder to apply as a cancer marker because the amount of good IgG is unknown. The analysis is exactly the same for IgA myeloma.

For my own amusement I plotted IgG and Spike on the same scale (Spike converted to mg/dL) going back five and a half years. You can see that Spike is always lower than IgG, though the difference has shrunk a lot in the last year since the beginning of the CC-4047 trial. I'll have to ask Dr L why that is:

Plateau!

Quick update:

I visited Mayo Clinic yesterday (Thursday) at the end of my 12th cycle on the trial drug CC-4047 with dexamethasone. Bottom line: M-Spike went down from 1.1 to 1.0 g/dL. In addition, IgG dropped from 1350 to 1160 mg/dL, strongly suggesting that the decrease is real and not just a testing anomaly.

The doctor used the work "plateau," and pointed out that the M-Spike hasn't really increased since last August, when it was lower than it had been in the previous three years. She even referred to the possible management of myeloma as a chronic illness rather than a fatal one, though we agreed that we don't yet know if that is appropriate in my case.

More information coming soon, in exhausting detail as always :-)

CC-4047 Cycle Eleven

Mayo Clinic Visit, January 8, 2009:

After eleven cycles of the trial drug CC-4047 and dexamethasone (DEX) my tumor burden may be starting to go up again. Last month's M-Spike was 1.0 g/dL and this month's is 1.1. The test-result printout, however, says "no significant change." And I suppose that's right. It's possible to read too much into one set of blood tests, and the accuracy of this test may not be much better than 10% anyway.

But previous tests and the results of other markers do suggest that the myeloma is coming back, if slowly. I hope not, but it seems most likely. In particular, IgG increased from 1260 to 1350, the third modest increase in the last three cycles. In contrast, though, Lambda Light Chains went down from 4.03 to 3.31 mg/dL, which might mean something, might not. They were up 24% last month, and this month they dropped back to about where they were.

Other numbers like calcium, creatinine, and albumin are fine, as is WBC the white blood cell count. AST and ALT, both a bit high last month, are back down into the reference range. Even RBC, the red blood cell count, has inched up into the reference range. So neither the myeloma nor the treatments are injuring any soft-tissue organs yet. I like that.

Here are some related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Oct 16		Nov 13		Dec 11		Jan 08		Remarks
M-spike g/dL		0.9		1.0		1.0		1.1		Best tumor measure
IgG mg/dL		1130		1170		1260		1350		Variation is normal
L FLC mg/dL		3.14		3.25		4.03		3.31		Free light chains
Calcium mg/dL		9.6		9.8		10.1		9.9		Below 10.2 is best
Creat mg/dL		1.1		0.9		1.0		1.1		Kidney, lower is better
HGB g/dL		13.8		14.6		14.6		15.3		Hemoglobin, normal
RBC M/uL		3.97		4.19		4.20		4.36		Red cell count, normal
WBC K/uL		4.4		4.3		5.3		4.6		White cells, normal

Supplements: For quite a long time now I've been taking a rather large number of different herbal supplements, many of them specifically intended to help treat the myeloma. Over the past three months, though, I've done an experiment. For one month I just skipped the supplements, and then for the next two I took them fairly religiously. I can't be perfect - it just isn't in me - but I did as well as I could. Results: (1) The tumor burden may have gone up marginally when I took NO supplements, and (2) It may also have gone up marginally in the two months that I DID take the supplements. In other words, I have no evidence that the supplements made any difference at all. None.

I can't prove that they DIDN'T help just a little bit, either, but that's not enough. Taking a fistfull of capsules twice a day is not a treat for me. In fact it's a huge pain in the butt. I hate taking them, and they cost a lot of money. So the supplements require a serious re-thinking. I will make an appointment with our naturopath and go through them, one by one, and come up with a shorter list. Much shorter, I hope. Maybe I can get it down to a fistfull ONCE a day. There are a few supplements that are quite safe on the list, such as saw palmetto for BPH (it's a guy thing), or Vitamins D3 and K2 for strengthening bones. Those are keepers. But curcumin, EGCG, quercetin, AHCC, and resveratrol are all up for grabs. On the other hand, Margaret has been posting good information about genistein lately, and our naturopath did recommend that a few months back, so perhaps it's worth a try.

Doctor: This time I met with the nurse-practitioner Dr KDS. Here is some of the discussion:

• I'm supposed to take a stomach-acid reducer with the weekly dexamethasone (DEX) to help ward off DEX-induced ulcer. I've experienced a slight stomach discomfort on ranitidine, so for one week I tried Prilosec, the other recommended option. Later I felt a sharp pain in the gut for a half day or so, possibly at a bend in the colon. I told Dr KDS that I had taken Prilosec but not for the recommended four days in advance, and she said that four days was not necessary. No explanation for the sharp pain, but back to ranitidine.
• I asked if there was any information or simple test that could tell us whether the lesions in my bones are getting larger or smaller. X-Ray bone surveys are very inaccurate, and the PET scan is not done often because of its cost. Sigh. We myelomiacs often don't know what the myeloma is doing to us until we break a bone. Seems like there should be a better way.
• I asked if the DEX and CC-4047 were making my body age rapidly, especially my skin. She thought probably so.
• I noted that skin is continuously renewing itself, sloughing off the top and rebuilding from underneath. If that rebuilding requires angiogenesis, the creation of miniscule blood vessels, then that rebuilding may be inhibited by CC-4047 and DEX, both of which are anti-angiogenic. She agreed that might be possible, even likely.
• I asked if there were any other organs which deteriorated under the CC-4047/DEX treatment. She suggested possibly the interior of the intestines, which are also lined with tissue that constantly sloughs off and renews itself from underneath. She thought NOT the more-critical organs like the heart, liver, and kidneys, which renew themselves in a different way.
• I asked about the herpes zoster (shingles) vaccine for myelomiacs like myself who have already had chicken pox. Dr KDS said it was risky for immune-compromised people because it is a live virus, and in addition the efficacy is not very high. In other words it's not worth the risk. Insurance doesn't cover it either.
• DEX is known to inhibit "glucose transport," the transfer of sugar from the blood into the muscles which need the sugar for fuel. I told her about a recent unintentional "experiment."   I ran seven miles on DEX day, when the DEX was at maximum effect, and finished totally exhausted even though my pace for that run was slow. The very next day I ran a similar distance at a faster pace, finishing with energy to spare. Neither of us was very surprised.
• I measured my blood glucose on DEX day again, this time with the 8 mg dosage. The chart below shows glucose measurements at 40, 20, 12, and 8 mg of DEX, always taken the evening before.

I'll go down to Mayo again in another month or so. Meantime I'm still running 20-30 miles per week, hoping to increase that gradually back up to 40. Life is good.

Elevated Blood Sugar Contributes to Memory Decline

Thanks to the web site Beating Myeloma for pointing out this New York Times article about a recent study reported in the Annals of Neurology, published by the American Neurological Association. The study of 240 elderly "nondemented" subjects was done at Columbia University Medical Center.

Key findings reported in the study abstract:

• People with diabetes tended to have hippocampal dysfunction, exhibited as memory decline, and
• Elevated blood glucose (sugar) was specifically implicated as the cause of this dysfunction.

I don't have access to the full article, but the New York Times author had the article and gives quotes from one of the authors. Here are some other findings and implications reported in that New York Times article:

• Using MRI, researchers actually observed reduced blood flow in key parts of the brains of people with elevated blood glucose;
• The effect (memory loss) can be observed even when levels of blood glucose are only moderately elevated;
• Glucose regulation worsens with age; and
• Though the age-related change may be subtle, the increase in blood glucose is still a risk.

Happily, though, we can all do something about this issue:

• Physical exercise has been shown to improve glucose regulation;
• Even light physical activity can help; and
• Weight loss has also been shown to improve glucose regulation.
• It is possible that drugs which lower blood sugar may help, but those studies are not complete.

Why does this matter to people who are not diabetic?

The study had nothing specifically to do with myeloma. However, those of us who are taking dexamethasone, prednisone, or another corticosteroid may have elevated blood sugar even though we don't have diabetes. We may be diabetics on DEX day. If so, the recent study suggests that we are also at risk for memory decline. What can we do?

• Exercise intentionally and regularly, and
• Maintain an ideal weight. Personally, Weight Watchers has worked for me.
• Eat well. Enjoy a plant-based diet, with grain and meat in moderation, and little or no empty carbohydrate. Vegetables, fruit, and nuts all contribute to our health, whereas soda pop and Twinkies detract from it.

What about the corticosteroid itself?

• If you're on high-dose dexamethasone (40 mg/day four days in a row), please discuss this dosage with your doctor. A landmark study has shown that high-dose DEX results in a lower survival rate than reduced dosages;
• Get a blood glucose monitor and measure your glucose several times over one day to see how well it is regulated.
• I use the Accu-Chek Active meter, which is very inexpensive and widely available. I think I bought it in a Target store.
• My non-medical opinion: Most readings should be below 125 mg/dL, especially the first reading of the morning before eating, but readings in the hour or two after meals may go higher and readings on DEX day may be higher. Any spikes over about 180 are a matter of concern.
• Again, I'm no doctor. You should bring the results and discuss the issue of steroids and blood glucose with your prescribing oncologist. If you are not totally comfortable with the answer, discuss it also with your primary care physician, who deals with diabetics on a daily basis and may know more about blood glucose than your oncologist.

Here is a personal story: After my initial visit to Mayo Clinic I was on CC-4047 daily with 40 mg dexamethasone (DEX) once weekly. Although my oncologist, Dr L, didn't ask me to do this, a couple of months later I measured my blood glucose on "DEX day," having taken the DEX the evening before. All of the 27 readings taken that day were above 120, and one was above 190. The average was 144. When I showed this to Dr L at our next appointment, she reduced my DEX dosage from 40 mg to 20 mg once weekly.

One point of that story is that the high blood glucose may have been harming me without any warning, because I didn't "feel" anything wrong. Another point is that we need to be in charge of our own health, and watch out especially for health issues that fall outside of the normal domain of our oncologists.

Be strong, be well.



Lunch: Leftover free-range no-hormone no-antibiotic bison potroast with onions, homemade organic pumpkin with pecans (crust-free pie), organic strawberries.

The Other Medications

I've written a lot about the Mayo Clinic & Celgene CC-4047 trial in which I am a participant. The major ingredients are CC-4047 (pomalidomide) and dexamethasone (DEX). But there are other drugs as well, that I haven't said much about:

• Aspirin, 325 mg daily.
• Acyclovir, 400 mg daily.
• Zantac (or generic ranitidine) with the dex.

Doctor L recommended all of these but didn't actually give me prescriptions, though I'm sure she would have if I had asked. The only one requiring a prescription is acyclovir, which is prescribed by my local internist.

Aspirin:

Recommended: 325 mg daily. I actually take two enteric-coated 81-mg tablets every morning with the acyclovir, and two more every evening with the CC-4047.

Aspirin reduces the likelihood of a deep-vein thrombosis (DVT). Both CC-4047 and DEX increase the probability of a DVT, and it is serious business. In my initial consultation with Dr L, I mentioned that when I was on thalidomide I had a pain in my calf, but I took a couple of aspirins and it went away. She leaned toward me, looked me straight in the eye, and said "YOU SHOULD NOT BE SELF-MEDICATING FOR A DVT!" Gulp. I guess I won't. The reason is that a DVT is a blood clot which can detach and travel to the lungs or the brain and cause heaps of trouble.

Aspirin can cause gastrointestinal ulcers. An enteric coating keeps the aspirin from being released until the tablet reaches the small intestine, where it is less apt to do harm. Most aspirin these days is enteric coated, which means that it is safer but does not work as rapidly.

In a recent presentation at a local support group meeting, a nurse told us that the amount of aspirin isn't critical. She said that aspirin has its effect on platelets, and once a platelet has been touched by aspirin it is changed and doesn't need more aspirin. Ever. Of course platelets die, and new ones are born, so daily aspirin is still necessary. I haven't googled this issue - just passing it along as if it were true.

A few months ago I asked my internist to do a coagulation check because of what I perceived as a bleeding problem. He did an INR and two other tests, but the results were perfectly normal. I was on daily aspirin at that time, same as now, so that's cool.


Acyclovir:

Recommended: 400 mg daily. I have a prescription from my internist for one 400-mg tablet daily.

Acyclovir is the generic name for an anti-viral medicine used to treat, among other things, various forms of herpes infections. In this case it is herpes zoster, also known as shingles, which can show up when a person's immune system is compromised, if that person has ever had chicken pox. I have.

Both CC-4047 and DEX can mess up the immune system. In fact DEX has a known and direct negative effect on the immune system. CC-4047, on the other hand, may enhance the immune system in several ways, at least as to the immune system versus myeloma cells (malignant plasma cells). Indeed, CC-4047 is known as an "immunomodulatory" drug, because it modifies the immune system. But CC-4047, like its relative Revlimid, may also decimate white cell counts, thus reducing the effectiveness of the immune system against herpes zoster.

While the normal use for acyclovir is to treat actual herpes outbreaks, daily acyclovir can inhibit some outbreaks and can reduce the intensity of outbreaks that do occur.


Ranitidine:

Recommendation: Dr L actually suggested either Zantac (ranitidine) or (I think) Prilosec (omeprazole), but my notes only seem to include Zantac. That was nine months ago, and now I don't remember why we didn't discuss Prilosec. She suggested taking a Zantac in the evening when I take the the DEX, and another the next morning when the DEX is having its maximum effect. There are two different strengths of ranitidine, 75 mg and 150 mg. I actually take generic ranitidine 75 mg tablets, one in the morning before DEX, one with the DEX, and the third the morning after DEX.

Ranitidine inhibits stomach acid production and is intended to treat heartburn. It should be taken 30 to 60 minutes prior to eating the food that would otherwise cause the heartburn. It has another beneficial effect, however: by reducing stomach acid it reduces the likelihood of gastrointestinal ulcers. DEX can contribute to ulcers, but the ranitidine may balance out that effect.

Omeprazole is a different kind of drug, called a proton pump inhibitor (who knew we have proton pumps?). It works more slowly, and I'd probably have to start at least a day in advance of the DEX, and take it for three or four days. I do get a very slight nausea from the ranitidine, so I might try the omeprazole some time, but not until I discuss it again with Dr L or her surrogate KDS.

Come to think of it, I should also ask Dr H, my naturopath, about ways to reduce the intestinal stress that causes ulcers.

I also take a slew of supplements.

The best web site for information on supplements is Margaret's Corner.



Salad & Dinner: Organic romaine lettuce, cucumber, boneless no-hormone no-antibiotics pork chops, organic cheese curds, avocado, Danish blue cheese, kiwi, filberts, organic broccoli, organic red wine vinegar.

Stable, With Caution

December 11, 2008:

My myeloma is stable after Cycle 10 of the CC-4047/Dexamethasone trial. Cool. But watch out for elevated liver enzymes AST and ALT.

This particular 28-day cycle may have been affected by several unusual circumstances:

• First, I really did take the supplements almost every day;
• I got a flu shot in mid-November;
• We enjoyed two days of Thanksgiving partying;
• Three weeks ago I pulled a band-aid off the back of my hand and unknowingly lifted the skin right off with it, leaving a large open sore;
• That sore developed a large (ugly) scab;
• Which does not look infected, but is healing very slowly;
• I got a 24-hour flu or food poisoning nine days before the Mayo appointment, including stomach upset and a slight fever, with a complete recovery by the next morning; and
• Something, who knows what, has caused liver enzymes ALT and AST to be elevated. ALT was 87 U/L, with a reference range of 7-52, and AST was 69 U/L, with a reference range of 15-37.

The Mayo test results don't indicate much change in the cancer numbers. M-Spike, the most significant number, is 1.0 g/dL, same as last month. In fact it has not changed much since August, the first time it dropped as low as 1.0. IgG is up from 1170 mg/dL to 1260, but for good reason, see below. Free lambda light chains are up 24% to 4.03 mg/dL, but kappa chains are up even more and the ratio actually went up a bit, so free light chains are probably not really up. The only scowl in the group photo is the elevated liver enzymes. Other blood numbers like red cells, hemoglobin, and platelets are as expected, with white cells and neutrophils increased as one might hope in response to a flu threat.

I go to Mayo every 28 days. I meet with Dr L every other time, otherwise with nurse practitioner KDS. This time it was Dr L. Here are a few subjects that came up:

• The increase in IgG might easily be attributable to the flu episode, because the immunoglobulins produced to battle the flu could last weeks in the blood.
• Similarly, the increased free lambda light chains could be coming from those plasma cells that produced the extra IgG. I think that's what she said.
• Dr L did not suggest a possible reason for the elevated liver enzymes, except maybe the flu episode. Especially if that was actually food poisoning and not flu. There was a now-suspect cheese ball ...
• Happily, two other liver markers are NOT up. Bilirubin was one of those, and I don't remember the other. LDH can be a liver marker but she didn't do LDH this time.
• The only albumin measurement this time was the one that comes as a part of the electrophoresis tests (with M-spike), and she doesn't quite trust that albumin result.
• However, that albumin result was UP to 3.6 g/dL from 3.4 the month before. It's a liver marker too, and UP is the preferable direction for albumin, trustworthy or not.
• In any case I will have the liver enzymes checked again in two weeks, the day before Christmas. If they are still up, it will probably be a dry Christmas for me. No beer. Sigh.
• I asked Dr L if there is any therapy for skin - some way to toughen it. She didn't know of any.
• Perhaps this is more the domain of Dr HH, the naturopath. Time for another appointment with her?
• People (more than one) have actually suggested Mayo Clinic's "Vanicream" skin lotion to strengthen skin. So we bought a couple of jars of that before returning home. I'll try it, what the heck.
• For what it's worth, the first ingredient is purified water, the second is white petrolatum, and the third is cetearyl alcohol. That third item is described in Wikipedia as not an 'alcohol' like rubbing alcohol, but rather a moisturizer, emulsifier, and stabilizer.
• She did suggest the use of heat to help heal the injury on my hand. I had been doing that in the beginning, with a glove to keep the area warm, but it's a good idea and I will try to wear it more faithfully.
• Dr L produced a chart on the computer that showed how CC-4047 (pomalidomide) stimulates the immune system in far more ways than thalidomide does.
• In contrast, dexamethasone suppresses the immune system.
• Yet the two together are more effective than either one alone. "Go figure," said Dr L. I guess there is more to be learned.
• Also, she believes that CC-4047 is strongly antiangiogenic, which means that it suppresses the creation of tiny new blood vessels. I got the impression that it exceeds thalidomide in this characteristic. Maybe Revlimid too. (CC-4047, Revlimid, and thalidomide are analogous immunomodulatory drugs.)
• We think that dexamethasone and other steroids are a cause of thinning skin.
• We also know that skin is constantly replenishing itself, wearing off from the outermost surface and rebuilding from below.
• I wondered if the rebuilding of skin might require the creation of tiny blood vessels, and if so, CC-4047 might interfere with the creation of new skin. She said that she always thought of the dex as the culprit in thin skin, but didn't discount this possibility either.
• Perhaps this could also account for the very slow rate of healing of injuries.
• Now I wonder if any other bodily organs might suffer from lack of an ability to rebuild. Does the heart rebuild itself? Lungs? Liver?
• I didn't discuss this with Dr L, but I notice that ALT and AST have been elevated before, in 2003 and 2004. Back then I believe that we attributed the temporary increase to running. I did a 5-mile run Wednesday night, less than 12 hours before this most-recent blood test. Could that be the cause? I'm thinking maybe so.
• The drive to Mayo is 90 minutes, and she gave me permission to drink black coffee on the way from now on, even though the first business on arrival is a blood draw. I will appreciate that.
• Of the 60 people in the CC-4047 trial, most are responding, including several for whom Revlimid has failed.
• One patient in particular was refractory to everything including Revlimid and Velcade, yet had an excellent response to CC-4047.
• Only two of the 60 patients are now progressing again.
• The generic name for CC-4047 will be pomalidomide, but the trade name will NOT be Actimid. Don't know what it will be.

Here are some related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Other side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Here are a few specific test results:

Test		Sep 16		Oct 16		Nov 13		Dec 11		Remarks
M-spike g/dL		1.0		0.9		1.0		1.0		Best tumor measure
IgG mg/dL		1180		1130		1170		1260		Variation is normal
L FLC mg/dL		2.64		3.14		3.25		4.03		Free light chains
Calcium mg/dL		9.7		9.6		9.8		10.1		Below 10.2 is best
Creat mg/dL		1.0		1.1		0.9		1.0		Kidney, lower is better
HGB g/dL		13.6		13.8		14.6		14.6		Hemoglobin, normal
RBC M/uL		3.90		3.97		4.19		4.20		Red cell count, low
WBC K/uL		5.3		4.4		4.3		5.3		White cells, normal

I'm still running 20 miles per week, getting set to increase that gradually back up to 40. Life is good.


Oatmeal breakfast: Gluten-free oatmeal, blueberries, organic walnuts, organic plum, organic low-fat milk, Dove dark chocolate, and "kiwi berries." We had not seen kiwi berries before. They are smaller than a kiwi with a nice, edible skin, and taste just like kiwis. Not organic, but we tried 'em and liked 'em.

Naughty Don

Edited and errors corrected Nov 18.

Perhaps the new CC-4047 drug has done the best it can. After nine four-week cycles in the phase-II trial, overall results are good but numbers are no longer improving. M-spike actually went up slightly this month for the first time, from 0.9 to 0.97, though still well down from the high of 2.7 at the start of the trial. This is also the first time that I have seen M-spike reported to the hundredths digit, though, so I wonder how significant that last digit really is, knowing that the electrophoresis test which measures M-spike isn't especially accurate anyway. IgG is virtually unchanged, and Lambda free-light chains (FLC) are up a little but so are Kappa light chains, and the ratio is unchanged.

White cell and red cell counts are mostly unchanged, also good. Hemoglobin is actually up a little. I bought a $25 blood pressure monitor and measured my blood pressure many times over the past few weeks, to get a better picture, and found that it is normal most of the time on the 12-mg dose of dexamethasone. Here is a chart of the blood pressure readings.

Because of muscle weakening, the doctor reduced my dex dosage from 12 mg per week to 8 mg per week for the upcoming 10th cycle. The entire protocol as prescribed by Dr. L is detailed in a previous post.

I skipped my supplements during this cycle, hence the "naughty Don" title. I didn't mean to at first, just forgot to take them, but when a week and a half had passed and I hadn't taken any yet, I decided to forget them for the rest of the cycle as an experiment. Result? This was the first cycle in which M-spike went up, if just a little. Maybe the supplements would have made a difference, maybe not, but I'm back on them now and we will see.

On this Mayo visit I met with Dr DS rather than Dr L, though Dr L did pop in for a moment. Dr DS is a certified nurse practitioner with special training in myeloma. She did a good job. I can't complain about my treatment at Mayo.

Here are some related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Other subjects that came up:

• The half-life of lambda and kappa light chains is just a few hours, and there is a constant race between the production of the light chains by plasma cells and their clearance by the kidneys. Several factors can influence the clearance, which is why the reported measurement of light chains may vary even if production is constant. Clearance is the same for both kappa and lambda, however, so the kappa/lambda ratio helps clarify whether an increase is real or not.
• Mayo uses a test called the Plasma Cell Labeling Index to determine the rate at which a person's myeloma is increasing. It involves a careful examination of the nuclei of many plasma cells. This test does correlate with actual patient experience, so it must mean (1) plasma cells really do clone themselves, or (2) the "memory B cells" which some think are responsible for creating new myeloma cells must be included in the blood sample being measured. Dr L thinks both are true, if I understood her response. Myeloma cells can clone themselves, at least to some extent, and the memory B cells can create them as well.
• We didn't discuss this, but here is what I think are the three names for the trial drug that I am on:
  • CC-4047: Code name used in drug trials;
  • Actimid: Brand name, like Revlimid is a brand name for lenalidomide;
  • Pomalidomide: Generic drug name, like lenalidomide is the generic name for Revlimid.

Here are a few specific test results:

Test		Aug 22		Sep 16		Oct 13		Nov 11		Remarks
M-spike g/dL		1.0		1.0		0.9		1.0		Best tumor measure
IgG mg/dL		1040		1180		1130		1170		Variation is normal
L FLC mg/dL		3.57		2.64		3.14		3.25		Free light chains
Calcium mg/dL		9.3		9.7		9.6		9.8		Below 10.2 is best
Creat mg/dL		1.3		1.0		1.1		0.9		Kidney, lower is better
HGB g/dL		13.8		13.6		13.8		14.6		Hemoglobin, slightly low
RBC M/uL		3.99		3.90		3.97		4.19		Red cell count, low
WBC K/uL		4.4		5.3		4.4		4.3		White cells, normal

I'm still running - three marathons since September. Nineteen states now, only 33 to go :-) Life is good.

Good News Again

October 16, 2008:

Eight four-week cycles of the phase-II trial of the new Celgene drug CC-4047 are now complete, and overall results are great. M-spike dropped again this month from 1.0 to 0.9, just a third of the high of 2.7 at the start of the trial. YAY! IgG is virtually unchanged, and Lambda free-light chains (FLC) are up a little but so are Kappa chains, and the ratio is actually a bit higher (better).

White cell and red cell counts are mostly unchanged, also good. Blood pressure, which was about 150/80 two months ago, was down to about 122/58 this month, probably because Dr. L has reduced my dosage of dexamethasone (dex) from 20 mg once weekly to 12 mg. That 12-mg dosage will continue for the ongoing ninth cycle. The entire protocol as prescribed by Dr. L is detailed in a previous post.

Here are some related links:

	My Myeloma		A discussion of my myeloma, not very technical.
	My Treatment History		Not technical.
	My Test Charts		Graphic displays of several key test results over time.
	My Test Result Table		Best with a wide browser window. Very "technical."

Side effects of the two key drugs, CC-4047 and dexamethasone, are discussed in a previous post.

Dexamethasone affects (increases) the level of glucose in blood, which is not good. Therefore, although I am not a diabetic, I occasionally use a blood glucose meter. In March, when I was taking 40 mg of dex, I measured blood glucose at roughly half-hour intervals on "dex day," and again several days later when the dex had worn off. In May, when taking 20 mg of dex, I measured it again on dex day. Last Monday was dex day once more, like all Mondays, and I made those measurements after taking 12 mg of dex the night before. Here is a chart that shows the results for 40 mg, 20 mg, 12 mg, and no dex. It's a busy chart, but the bottom line is: 12 mg of dex last Monday resulted in blood glucose levels at least as high as they were with 20 mg of dex last May 19, almost five months ago. That was a surprise to me but not to Dr L, see the first item below.

Some subjects that came up:

• It appears that a person's sensitivity to dexamethasone increases with use. Therefore, after a time, a lower dosage of dex will produce much the same effect as a higher dosage did previously. We were discussing side effects when Dr L mentioned this, so I do not know if that also applies to the anti-myeloma benefit of dex.
• I asked whether or not it was time to harvest stem cells against the eventuality of a stem cell transplant. Dr L responded that the CC-4047 phase-II trial protocol does not provide for the interruption required for a harvest, so I guess I will wait until the trial is over. I'm OK with that - the trial will not end for me as long as it continues to reduce my counts or hold them steady, and there is NO chance that I will want a transplant until CC-4047 fails to do that.
• Long-term dex usage can cause avascular necrosis of the bone, which is bone death attributable to insufficient blood supply. Most commonly this occurs in the hip, at the head of the femur, but it can happen in other places. I asked if I was a candidate and Dr L said it was possible, though I got the idea that I'm not really into "long-term" yet after only eight months. Further, she did not indicate that the risk was very high. I would like to think that my highly-active lifestyle might help too, but we did not discuss that.
• I asked about the half-life of myeloma cells, and she thought that it would be a property of a person's particular myeloma and would vary a great deal from one individual to another, though probably measured in months in most cases.
• The half-life of normal plasma cells is also quite variable. They are responsive to threats perceived by the body, and a few of them even become "memory B cells," which live for a very long time and retain patterns for the immunoglobulins required to neutralize the threats they have seen.
• We did not discuss this, but I believe that researchers at Johns Hopkins have identified some of these "memory B cells" as the wacko and hard-to-kill progenitors of new myeloma cells.
• Dr L recommended the flu shot and suggested November as the best time to get it. Since the shot has a limited period of effectiveness, November constitutes a balancing of the risk in the fall versus the risk in the spring.
• The Myeloma group at Mayo is moving from the Gonda Building to the Mayo Building on November 1.
• She asked about muscle weakness, particularly in the shoulders, upper arms, and quads. I am not having any problems, except that it takes an hour longer now to finish a marathon. I'll get back to my resistance exercises and try to quantify any other muscle losses.
• CC-4047 seems to be less "myelosuppressive" than Revlimid, which means that it does not harm the cells of the bone marrow so much and therefore does not suppress red and white cell counts as much. In my case there is only a barely-noticeable difference attributable to the CC-4047/dexamethasone trial.
• We discussed nifuroxazide, the subject of a recent article in Blood Journal. It's a 40-year-old antibiotic, used especially in Europe, for treatment of certain types of diarrhea. Researchers in Boston have recently discovered that it can selectively kill myeloma cells in the lab, though no studies have been done with real live humans yet. I learned of this from Beating-Myeloma, and I think it was new to Dr L. She cautioned that it's still a long way from actual use by patients, of course. Nevertheless, I suppose that if I were at the end of the treatment road and nothing else was working, I'd want to try it.
• My blood pressure has been a bit high in some of the most-recent Mayo visits, though it wasn't this time. I supposed that it should be a little higher for a person whose heart rate is low. The person needs as much blood as anyone else, and the heart doesn't have as many opportunities to pump it, so it has to pump harder on each beat, hence higher pressure. I was unable to convince her, though, because there are so many other variables and, as she said, blood pressure is more a function of the blood vessels than the heart.

Here are a few specific test results:

Test		Jul 24		Aug 22		Sep 16		Oct 16		Remarks
M-spike g/dL		1.1		1.0		1.0		0.9		Best tumor measure
IgG mg/dL		1360		1040		1180		1130		Variation is normal
L FLC mg/dL		3.30		3.57		2.64		3.14		Free light chains
Calcium mg/dL		9.7		9.3		9.7		9.6		Below 10.2 is best
Creat mg/dL		1.0		1.3		1.0		1.1		Kidney, lower is better
HGB g/dL		14.3		13.8		13.6		13.8		Hemoglobin, a bit low
RBC M/uL		4.17		3.99		3.90		3.97		Red cell count, low
WBC K/uL		4.7		4.4		5.3		4.4		White cells, normal

Red cell count and hemoglobin are on the low edge. I will continue to try to improve those numbers those with sublingual B-12 for another month, but it doesn't seem to make a difference.

Meanwhile I just ran another marathon and life is good.

The graph here shows results from 40, 20, 12, and 0 mg dex. Results from 20 mg (May) and 12 mg (Oct) are very similar, presumably because my system became more sensitive to dex in the interim. Click to enlarge.