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.

Stable

September 16, 2008:

Seven 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 is unchanged this month at 1.0, but down from a high of 2.7 at the start of the trial. IgG is up a little but I have a cold which can make it go up, and Lambda free-light chains (FLC) are at the lowest level in five years of measuring them. Doctor L used the word "stable" to describe my myeloma. Stable is good.

White cell and red cell counts are mostly unchanged, also good. Blood pressure, which was about 150/80 last month, was down this month, probably because Dr. L reduced my dosage of dexamethasone (dex) from 20 mg once weekly to 12 mg. That 12-mg dosage continues for the ongoing eighth cycle. This is the entire protocol as prescribed by Dr. L:

• 2 mg CC-4047 every day, no days off. I take it at bedtime.
• 12 mg dexamethasone once weekly. I take it with Sunday supper, so Monday is "dex day" for me.
• 325 mg generic aspirin daily, to prevent deep-vein thrombosis (DVT). I take half in the morning and half with the CC-4047.
• 75 mg generic ranitidine (Zantac) twice on Sunday and once Monday morning, to mitigate stomach problems from the dex.
• 400 mg generic acyclovir daily, to stave off shingles.

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 side effects of dex are mostly reversible, except for cataracts. So far I haven't had that problem.
• Would lutein be of value in fending off cataracts? Curious minds want to know. Eat your Brussels sprouts.
• Every myeloma treatment works better with dex than without. Darn.
• The half-life of the IgG protein, whether monoclonal or normal, is four to six weeks (!).
• IgG is a measurement of all immunoglobulin G proteins, while M-spike measures only the monoclonal part of IgG.
• The half-life of light chains is two or three hours.
• Hence the light chains can be a more-current snapshot of what's going on, compared with IgG or M-spike.
• Events in the body can make light chains go up and down, but kappa and lambda normally go up and down together.
• The exception is myeloma, which makes one go up independently. This is why the ratio of kappa to lambda is useful.
• Celgene seems to be calling CC-4047 "pomalidomide" now. But it still says CC-4047 on the bottle of capsules that I get.
• Revlimid can cause thyroiditis, causing the thyroid to first become overactive and later become underactive (hypothyroid).
• Since CC-4047 could have a similar side effect, Dr. L checks my thyroid every three cycles. So far so good.
• CC-4047 appears to have much less effect on white and red cell counts than Revlimid, which can depress counts substantially.

Here are a few specific test results:

Test		Jun 26		Jul 24		Aug 22		Sep 16		Remarks
M-spike g/dL		1.1		1.1		1.0		1.0		Best tumor measure
IgG mg/dL		1450		1330		1040		1180		Variation is normal
L FLC mg/dL		4.03		3.30		3.57		2.64		Free light chains
Calcium mg/dL		10.1		9.7		9.3		9.7		Below 10.2 is best
Creat mg/dL		1.0		1.0		1.3		1.0		Kidney, lower is better
HGB g/dL		14.8		14.3		13.8		13.6		Hemoglobin, a bit low
RBC M/uL		4.28		4.17		3.99		3.90		Red cell count, low
WBC K/uL		5.5		4.7		4.4		5.3		White cells, normal

Red cell count and hemoglobin are on the low edge. I will continue to try to treat those with sublingual B-12 for another month.

Meanwhile I'm still running and life is good.



Breakfast: Don't you love berry season? Still possible to get some good ones. There's oatmeal under there somewhere.

Mayo Clinic Visit Aug 22

We celebrate the end of cycle six of the phase-II trial of the new drug CC-4047 with dexamethasone (dex). The first three monthly cycles brought very good results, then the fourth and fifth cycles not so much, but this sixth cycle seems to point to a continuing gradual decline in tumor burden. My two primary markers are IgG and M-spike. In this sixth cycle:

• IgG dropped 23%, from 1360 down to 1040 mg/dL, lower than it has ever been before in five years of watching it. IgG does bounce around, though, as the immunoglobulins respond to internal bacterial and viral infections, so it could pop back up again in a month. Or not.
• M-spike went down 9%, from 1.1 to 1.0 g/dL. It is the best measure of monoclonal protein, which in turn is the best measure of total tumor burden other than a bone marrow biopsy. The ideal (and normal) value is zero.

The good news is:

1. The cancer does seem to be declining, if rather slowly, and
2. There really isn't any bad news.
3. Life is great!

Dr. L took my blood pressure two different ways and got numbers close to 150/80 each time, higher readings than I have ever had before. Ever. Maybe that's the bad news. I'm not too worried yet, though, because I have recently had very normal blood pressure readings too. Shouldn't my blood pressure be a bit high when visiting my oncologist? Yes, but maybe not in this case because she had already told me that the tumor burden seems to be going down.

Regardless, Dr. L knows that dexamethasone can cause high blood pressure, and is aware of the risks that it brings. She is concerned enough that she has reduced my weekly dose of dex from 20 mg to 12 mg. This does NOT displease me! I hate dex - I just ran a half marathon race ten minutes slower than one I ran in May, and I attribute most of the loss of speed to dex. I wonder what else it's doing to my body. Of course I hope that the reduction in dex will not significantly reduce the efficacy of the treatment.

We will continue with 2 mg of CC-4047 daily and 12 mg DEX once weekly for the seventh cycle. 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 drugs, CC-4047 and dex, are discussed in a previous post.

Other subjects that came up:

• Some people take their dexamethasone in the morning and some take it in the evening, so I asked if there is any difference in efficacy. Dr L said not, but there may be a difference in side effects, especially regarding sleep. Since I am not having much problem sleeping, I will continue to take it with dinner.
• I asked if normal plasma cells can replicate themselves. Dr L said that they do not replicate directly, but through progenitors called "memory B cells." These are the same cells that some researchers suspect of going wacko (technical term) and creating defective plasma (myeloma) cells in great quantity. These progenitor cells are also resistant to the usual treatments, like CC-4047 and dex, which may be why myeloma always comes back. Researchers are actively working on ways to eliminate the wacko progenitor cells.
• The treatment is reducing my markers rather slowly, so I asked if that predicted a poor outcome. She said that it may be just the opposite - that a fast treatment response can be followed by a fast return of the cancer, and that a slow response like mine is consistent with other indicators suggesting that my cancer moves slowly. She also said that a slow but consistent downward trend in markers is often seen in people taking Revlimid and CC-4047.
• I was initially diagnosed with "light chain-disease" five years ago, so I asked Dr L if I really do have light-chain disease. She preferred the term "light-chain deposition disease," and said that I do not have it. Apparently I have a rather garden-variety myeloma with an incidental, minor secretion of lambda light chains. In other words the myeloma cells themselves are the problem, not the the light chains, and that's actually a good thing.

Here are a few specific test results:

Test		May 29		Jun 26		Jul 24		Aug 22		Remarks
IgG mg/dL		1260		1450		1330		1040		Variation is normal
M-spike g/dL		1.2		1.1		1.1		1.0		Best tumor measure
L FLC mg/dL		4.25		4.03		3.30		3.57		Down is best
Calcium mg/dL		9.7		10.1		9.7		9.3		Below 1.2 is best
Creat mg/dL		1.1		1.0		1.0		1.3		Kidney, lower is better
HGB g/dL		14.5		14.8		14.3		13.8		Hemoglobin, a bit low
RBC M/uL		4.23		4.28		4.17		3.99		Red cell count, low

I'm no longer concerned about lambda free light chains (L FLC). Calcium is dandy. Creatinine is up, but it has been this high in the past. Hemoglobin and red blood cell count are down, but they have been lower. Albumin (liver function, not shown) is normal.

I feel so very lucky, still able to finish a half marathon when I know so many myelomiacs who could not. Live one day at a time and make it a masterpiece!

		Dinner 1: Wild-caught sole pan-fried with ancho pepper, organic broccoli with parmesan cheese, organic nectarine, organic lime.
Dinner 2: Grass-fed free-range beef, organic plum, organic broccoli with parmesan cheese.
		Dinner 3: Free-range grass-fed chicken breast, vidalia onion, organic nectarine, vegetable quiche with organic baby spinach, organic tomato, vidalia onion, parmesan cheese, organic egg.

Naturopath Visit

Sunshine and I went to see the naturopath Dr HH last Thursday, with two major issues:

Stable Disease Despite Treatment:

My IgG and M-Spike have been almost level for two months now, even though I have been on the drug trial which includes CC-4047 and dexamethasone (dex). So what can I do to change things, to make the drugs work better? Discussion:

• Dr HH started by suggesting "proteolytic enzymes," which in some studies have significantly improved the outcomes of chemotherapy. Here is one example (read down the page a ways). I've already started taking the enzymes between meals.
• In addition, she suggested that I eat more meat! Naturopaths tend to lean toward the vegetarian end of the chow spectrum, so she admitted that this was strange for her, but she thinks I might benefit from red meat: beef, lamb, bison, mutton, venison, salmon, and perhaps not so much chicken as I eat now. Huh. We originally cut back on meat to reduce inflammation, but my inflammation markers are quite low, so I'm up for this change.
• I am currently taking reishi mushroom, and Dr HH suggested a more potent variety known as AHCC (Active Hexose Correlated Compound). I will order some. Naturally, it's quite a LOT more expensive than the reishi.
• Myeloma is not just any cancer - it is a cancer OF the immune system. Therefore, we always have before us the question: "Should we do things that are intended to bolster the immune system, or should we not?" I asked her to go through the list of supplements that I have been taking, with an eye toward eliminating any that may not seem necessary, and especially any that are only intended to boost the immune system in non-specific ways. We struck several off the list. In particular, we eliminated:
  • Coenzyme Q-10, of all things. Co-Q10 supports mitochondrial function, and is thought to be a very good supplement, but it's possible that the mechanism by which CC-4047 kills naughty plasma cells may involve interfering with mitochondrial function. If so, then Co-Q10 could be working against the CC-4047. I'm in way over my head here, but for at least a month I'm going to cut back on C0-Q10.
  • Borage Oil. I ran across one obscure reference suggesting that borage oil can decrease NK cell activity, which is probably not good. His claims are unsubstantiated, but for now, I'll stop it.
  • Others. The link to the right labeled My Supplement Regimen shows the old list with several supplements crossed out.

Mitigation of Damage from Dexamethasone:

Dexamethasone is an important part of the treatment, but it does have significant side effects. It can cause muscle wasting and accumulation of fat around the stomach, and it causes insulin resistance very much like that of a diabetic. In fact, it can make a person a diabetic. Bad stuff, and oncologists may not have much advice to offer about reducing side effects. Discussion:

• Carbohydrates are not good on dex days, because they change to glucose and the dexamethasone interferes with "glucose transport." This prevents the organs and muscles from absorbing glucose, resulting in fat buildup instead. Something similar happens to ingested fat. This leaves protein as the preferred nutrient, which does fit well with the new higher-meat diet. So the plan is to reduce carbs and fat on "dex days" (the two days after taking dex), and eat plenty of protein, but reduce total calories to prevent fat accumulation. Anyway, that's the plan.
• Add a chromium supplement, because chromium can improve glucose transport. Up to as much as 1000 micrograms per day. And hope that the mechanism by which dex kills myeloma plasma cells is NOT by interfering with glucose transport to those cells. Yikes.
• On dex days, aerobic exercise is difficult because the muscles run out of glycogen and cannot easily replenish it. Dr HH suggested doing resistance training on those days instead, because that will not significantly depelete glycogen stores but will nevertheless teach muscles to build themselves instead of growing smaller.

The idea is to shake things up and try to create movement in the M-spike and IgG. Hopefully that movement would be down, but either way we would learn something.



Dinner: Organic chicken w ancho pepper, vegetable curry with organic sweet potato, organic zucchini, organic carrots, organic chard, onions, and organic strawberries.

Glass Half Full

In early March I joined a phase-2 trial (study) of Celgene's new IMiD drug CC-4047, with once-weekly dexamethasone. The first three one-month cycles brought very good results, each with approximately a 25% reduction in markers, but the fourth and fifth cycles have been less spectacular. My two primary markers are IgG and M-spike:

• IgG actually went up 15% in the fourth cycle, then down half of that difference in the fifth to a value of 1360 mg/dL. IgG does bounce around, though, as it responds to internal bacterial and viral infections, so the meaning is not clear.
• M-spike went down from 1.2 to 1.1 g/dL in the fourth cycle, then stayed at 1.1 in the fifth. It is the best measure of monoclonal protein, which in turn is the best measure of total tumor burden other than a bone marrow biopsy (ouch), but it may only be repeatable to 5% or 10%. Zero is the ideal value. Lambda free light chains are down 22% over the two months, which must be a good thing. They can be another measure of tumor burden for some people, though we haven't been focusing on them in my case.

So the bad news is that there is no change, at least none for sure. The good news is that there is no indication at all that the tumor burden is climbing again, as it had at every test for the previous five years. More important, IgG is in a "normal" range and M-Spike is at a value last seen three years ago. I hope for more improvement, but if none comes I'm still far better off than before I started on the drug trial. Life is great!

We will continue with 2 mg of CC-4047 daily and 20 mg DEX once weekly for the sixth cycle. 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 drugs, CC-4047 and dexamethasone (DEX), are described in a previous post.

Other things that came up:

• Much of the appointment this time was handled by KD, a certified nurse practitioner, who asked most of the questions and actually performed the hands-on part of the checkup. Evidently this will be the new normal, with KD or Dr L checking me out on alternate months. This time Dr L did come in for a while, to answer my little list of questions, and I don't know if that is part of the new normal.
• I asked if there was any resource to get advice about mitigating the effects of dexamethasone, and Dr L wasn't aware of any. Just exercise and a high-protein diet. Guess it's up to me to find or create the resource.
• HHV-8 was discussed at length in some blog comments (see earlier post). Dr L said that there was a time when some doctors were quite excited about a perceived link between myeloma and HHV-8, but since that time no one has been able to reproduce their results.
• Lipids - we checked mine for the first time in many years: Total cholesterol 168, HDL 42, LDL 109, triglycerides 83. I'd like the HDL to be a tad higher and LDL a bit lower, but I'll take it.

Here are a few specific test results:

Test		May 29		Jun 26		Jul 24		Remarks
IgG mg/dL		1260		1450		1330		Some variation is normal
M-spike g/dL		1.2		1.1		1.1		Best tumor measure
L FLC mg/dL		4.25		4.03		3.30		Down is good
Calcium mg/dL		9.7		10.1		9.7		Below 1.2 is best
Creat mg/dL		1.1		1.0		1.0		Liver function, low is better

	Post-run breakfast: Gluten-free oatmeal with organic flame raisins and dried cranberries, blueberries, organic apricot, organic walnuts, mango, papaya, dark chocolate, organic pomegranate juice, organic nonfat milk.
Dex lunch, low carbs and high protein: Organic pork chop, organic broccoli with shredded parmesan cheese, organic cherries.
	Dinner: Organic chicken with onions and brown rice, organic nectarine, organic mixed vegetables with shredded parmesan cheese.

Cool Calendar Program

We recently discovered a nice calendar program called Mozilla Sunbird. If you are interested, here is a post about it.

Diabetic for a Day

Or two. DEX makes us temporarily diabetic by messing with the glucose transport system, which decreases the body's normal ability to move glucose out of the blood and into muscles and other organs.

I have a blood glucose monitor and did a simple study of my own blood glucose, taking a reading every half hour or so all day long, on four different sore-fingered days. Here is the bottom line result, where Day 1 is the next day after taking the DEX the previous evening. The "glucose" value is an average for the whole day, expressed in mg/dL:

Day	Dose mg	Glucose	Comment
1	40	144	Highest was 193
2	40	101
5	40	88	DEX effect must be gone
1	20	116

More information about this little personal "study" is detailed in earlier blog posts HERE and HERE. Graphics included. The graph here shows Days 1, 2, & 5 on 40 mg DEX.

I am NO expert in diabetes, but when Dr. L at Mayo saw the graphics and numbers for Day 1, she reduced my DEX dosage from 40 mg to 20 mg. The glucose spike of 193 mg/dL seemed to be a particularly important factor. Fasting glucose for a non-diabetic should be in the range of 80 to 120, and diabetics are urged to keep their glucose, fasting or not, below 180.

Many diabetics will need insulin shots along with a careful diet, but those of us who are not normally diabetic already have the insulin, except that its effect is inhibited by the DEX. Therefore we need to manage our temporary DEX-induced "diabetes" at least partly through diet. When I asked Dr. L about this, she commented that several of her patients are eating a low-carb diet on DEX day.

Here is a set of dietary principles that I have recently been following, with the help of Sunshine and Sweet Pea (they're the cooks!), on DEX day 1 and, to some extent, on Day 2:

• Most important: Keep the amount of food modest, because all food raises blood sugar. I do this with Weight Watchers "journaling," but calorie counting would work too;
• Reduce carbohydrates in favor of protein, and good fats such as nut oils, olive oil, and fish oils;
• Prefer carbohydrates with a low glycemic index, to reduce the glucose spike;
• Eat some of the protein and fat first at each meal, because this slows the entire digestive process and thereby moderates the glucose spike;
• Good food: Chicken, fish, vegetables, nuts, eggs, certain fruits and berries, legumes, whole-grain foods; and
• Bad food: Sugar (except fructose), soda, potato, candy, white bread or any relative, (the list goes on).

One caution: People whose kidneys are already at risk should be careful about increasing protein, and every myelomiac should take plenty of fluid to help the kidneys. As always CONSULT YOUR DOCTOR! But don't settle for "oh, don't worry about it." This is real, and somewhat outside the experience of many oncologists. Know what you are talking about, be your own advocate, and press a little. If you're interested, a blood glucose monitor costs between $30 and $100 with supplies.

You might notice that the foods that we eat on the DEX diet are foods that are really good for us anyway, and delicious. Those that are bad are ones that we never eat, ever. We just tilt the balance of protein, fat, and carbohydrates. So except for the protein issue for those with kidney disease, there is no downside to eating like a diabetic for a day or two. The food can be wonderful!

I wholeheartedly invite your comments, pro or con, and I especially hope that you will straighten me out if I have made any errors, or share with us if you have something to add.

Examples of DEX day meals that I have recently eaten. Oh, the suffering that we put ourselves through :-)

Today's DEX lunch: Organic chicken breast, Jim's broccoli, dill cheese, organic strawberries. Weight Watchers points = 6.


Today's DEX salad: Organic romaine, cucumber, avocado, organic cashews, organic strawberries, pecans, organic red wine vinegar. Weight Watchers points = 6.


Yesterday's DEX dinner: Wild-caught Alaskan sockeye salmon, organic lime, Jim's organic beet greens, spinach, and onions, with a few organic raisins, plus orange and mango. Weight Watchers points = 8.

Equivocal Results

In early March I joined a phase-2 trial (study) of Celgene's new IMiD drug CC-4047, with once-weekly dexamethasone. The first three cycles brought very good results, each with approximately a 25% reduction in markers, but this fourth cycle was less spectacular. My two primary markers are IgG and M-spike:

• IgG is actually up 15%, definitely the wrong direction and suggesting an increase in monoclonal protein. However, IgG has a normal variation because it responds to bacterial and viral threats to the body, so the increase may be entirely normal and could mask an actual decrease in monoclonal protein.
• M-spike is down 8%, and although that test is the best measure of monoclonal protein, it may only be accurate to 5% or 10%. Lambda free light chains are also down slightly, however, which does lend more credence to an actual decrease in M-spike.

I get to interpret these results as I please, and I say that there is a modest decrease in monoclonal protein and therefore, most likely, a decrease in tumor burden. So there.

Side effects of the two drugs, CC-4047 and dexamethasone (DEX), are described in a previous post.

We will continue with 2 mg of CC-4047 daily and 20 mg DEX once weekly for the fifth cycle. Here are some related links:

	My Myeloma		A discussion of my myeloma.
	My Treatment History		Not technical.
	My Test Charts		Charts of key results over time.
	My Test Result Table		Needs a wide browser window. Technical.

Other things that Sunshine and I discussed with Dr. L today:

• I have noticed a slightly irregular heartbeat, an occasional extra beat actually, on two mornings while laying in bed on my left side, both times a day or two after taking the DEX. The irregularity goes away if I move off my left side. Neither Dr. L nor I are very concerned about it.
• I am NO fan of DEX, but for a day or two after taking it I do notice some unexpected benefits:
  • My chronic headache disappears and I don't need to take my usual naproxen;
  • My BPH also disappears; and
  • So does my nighttime stuffy nose, for which I otherwise take a nightly nasal spray.
• The meaning of LDH: It is a non-specific marker of "cell turnover" (cell death) which was once of some value in prognosis for a newly-diagnosed patient because it correlated inversely with survival. However, other problems such as heart disease can also give rise to high LDH, resulting in an incorrect cancer prognosis. Newer markers are much more specific to myeloma, and Dr. L wondered if LDH should even be included in the standard battery of tests any more.
• I asked why the myeloma drives IgA and IgM (in my case) so low, and Dr L responded that the reason for that is not yet well understood.
• Though I'm a long way from "remission" at this point, we discussed the three treatment options that seem to be available after remission is achieved: (1) Continue treatment; (2) Continue treatment at a reduced dosage or frequency; or (3) Stop treatment and wait watchfully. Dr. L confirmed that the studies which have been done thus far do not clearly indicate a survival advantage for any of the three.

Here are a few specific test results:

Test		5/29		6/26		Remarks
IgG mg/dL		1260		1450		May be a normal immune response
M-spike g/dL		1.2		1.1		I hope this is real!
L FLC mg/dL		4.25		4.03		Down is good
Calcium mg/dL		9.7		10.1		Hopefully just a normal swing

In addition, the absolute neutrophil count (ANC) dropped from 2.41 last time to 1.65 this time. This could indicate that the CC-4047 is suppressing the neutrophils, and if that happens we will have to change the test regimen. However, there is a note in the results saying that the ANC was derived in a different way this time and may not be comparable to previous results.

I'm more concerned about a remark in the CBC results saying that "toxic neutrophils" are present. I'm not quite sure, but I think it means that my body actually is dealing with a minor infection (I do have a sore nose), or maybe a muscle-repair job from the marathon that I just ran.

Perhaps I'll call Dr. L.

Friday, June 27: Dr. L says it's nothing to be worried about, probably just a normal response to a minor infection or other threat, so I won't worry.


Fruity breakfast: Gluten-free oatmeal, organic flame raisins and dried cranberries, organic strawberries, organic nectarine, blueberries, organic cashews, mango, organic pomegranate juice, organic nonfat milk.

Agent Orange

Vietnam veterans and other veterans who have myeloma and who may have been exposed to the herbicide/defoliant Agent Orange are eligible for benefits from the Veterans Administration and other agencies. There is no conclusive evidence that Agent Orange causes myeloma, but there is some evidence and it is acceptable to the Veterans Administration. If you are a veteran who was exposed to Agent Orange, then you may know the cause of your cancer.

But what about those of us who were not in the military and certainly were not knowingly exposed to Agent Orange. It is quite possible that we WERE exposed, not to Agent Orange but to other commonly-used commercial weed killers containing the same ingredients as Agent Orange. One of those, widely available in the USA and fairly typical, was Ortho Weed-B-Gon, which once contained two primary ingredients: 2,4-Dichlorophenoxyacetic acid (2,4-D); and 2,4,5-Trichlorophenoxyacetic acid (2,4,5-T).

The second ingredient, 2,4,5-T, was also marketed separately under the brand name Silvex. It contained a dioxin called TCDD, produced as an inevitable by-product of manufacture. TCDD is toxic to humans in the smallest qualtities, and was banned for use on agricultural crops in 1970, but remained in use for lawn weed control until 1985. TCDD can cause cancer 20 years or more after exposure.

The first ingredient, 2,4-D, is still widely in use in the USA, most European countries, and most of the rest of the world. Most government agencies have concluded that it is safe. However, a different dioxin called DCDD is present in 2,4-D, and some believe that DCDD may be as harmful to humans as TCDD. It is banned for use on lawns in a few countries including Denmark, Sweden, and Norway.

Agent Orange was a mixture of approximately equal parts of 2,4,D and 2,4,5-T. Commercial lawn preparations of the 1950's, 60's and 70's typically included more 2,4,D than 2,4,5-T, but only a little 2,4,5-T could contain enough dioxin to be harmful.

Personally, I have used Weed-B-Gon nearly every year since the late 1950's. I have sprayed thousands of gallons of that stuff, some of it on dandilions and much of it to control poison ivy. Most recently, of course, Weed-B-Gon has not contained 2,4,5-T with its TCDD dioxin, but it always contains 2,4-D with DCDD. Was my myeloma caused by exposure to 2,4,5-T twenty, thirty, or even fifty years ago? Was it caused by 2,4-D more recently? We'll probably never know. But you may be sure I'll be wearing a very high-quality mask the next time I attack that poison ivy. No more bare-faced Don.



Breakfast with lots of antioxidants: Gluten-free oatmeal with organic flame raisins and dried cranberries, mango, organic strawberries, banana, blueberries, cashews, organic pomegranate juice, organic nonfat milk.

Good News from ASCO

The International Myeloma Foundation (IMF) has posted a news article announcing findings presented at the American Society of Clinical Oncology (ASCO) last week indicating that "novel" treatment options such as Revlimid and Velcade have significantly improved patients' survival. In particular:

• Two-year survival has increased to 93% for newly-diagnosed patients. The survival rate for people without myeloma is only three percent higher,
• Velcade has produced a high complete-response (CR) rate, and
• Further improvements are made by using Revlimid and Velcade in sequence or in combination.

The IMF believes that we are coming closer to making myeloma a chronic disease instead of a fatal one.

Stick around, it's getting better and better!

CC-4047 Rocks Again

Three months ago I enrolled in a phase-2 trial (study) of Celgene's new IMiD drug CC-4047, with once-weekly dexamethasone. This third cycle brought another good result. My two primary markers, IgG and M-spike, are both down more than 50% after three months. This is an excellent response, especially since I stopped responding last year to thalidomide, a relative of CC-4047. I know that other patients have done well too. CC-4047 is not a cure for myeloma, but it may become a very important tool in managing it and an actual lifesaver for some who have exhausted other options. I hope it becomes more widely available SOON.

CC-4047 side effects for me:

• Bradycardia - my resting heart rate has dropped from about 48 to about 41.
• Slight reduction in red cell count and hemoglobin, taking both just below the reference range.
• Tinnitus from the aspirin that I take with the CC-4047.

No neuropathy, thromboses, leukopenia, neutropenia, or other difficult side effects yet, though these are all possible.

Dexamethasone side effects:

• "Peppy" and not-so-peppy days, fitful sleep one day a week.
• Increase in belly fat - I'm pretty sure this is happening.
• Loss of muscle mass, especially quads - my running speed is declining.
• High blood sugar levels on "dex day," as measured with glucose monitor.
• Thinning of my skin; it seems quite fragile now.
• Dex voice (tight).

Considering the good response and the dex side effects, Dr. L reduced the dex dosage from 40 mg to 20 mg once weekly for the third cycle just completed. We will continue with 20 mg for the fourth cycle.

I'm lucky, or blessed, in so many ways. Though I can't run as fast as I once could, that's unimportant in the big picture. Most important, myeloma has not yet hurt me. Aside from painless lesions inside three bones, I have no symptoms from the disease itself, and symptoms from the treatment are quite livable thus far. I wish that all myeloma survivors were so lucky, or blessed. Thank you for your prayers, and I offer you mine.

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 things that Sunshine and I discussed with Dr. L:

• The loss of muscle mass and the thin skin, both caused by dex, may be reversible if I can ever stop using dex.
• There is not enough information yet on CC-4047, or on its relative Revlimid, to know if either drug is likely to cause other cancers or to change the myeloma to a more aggressive type. So far so good.
• The absolute amount of drop in IgG and M-Spike seems to be somewhat less for each successive cycle, and that trend is likely to continue. It's the direction that is important. I notice that the drop in IgG as a percentage of the previous measurement has been about the same from cycle to cycle, about 25%.
• I expressed the view that since the current treatment is working and there are lots of other treatments available, I might expect not to die from myeloma for five or ten years even without any advances in treatment. Dr. L thought that was not an unrealistic expectation. Cool.
• We talked about running a little too. :-)

A late-arriving result: Dr. L had my blood checked for stored ferritin, with a result of 32 ug/L compared with a reference range of 24 to 336 ug/L. It's on the low side; I need to research this and maybe discuss with my naturopath, Dr. H.



Tonight's celebration salad: Organic romaine, cucumber, organic walnuts, avocado, organic strawberries, blue cheese, organic red wine vinegar, organic pomegranate juice.

Dex and Blood Sugar, Part 3

In early April I did a little experiment, measuring my blood glucose approximately every half hour on three different days: (1) Dex day (after taking dex the night before), (2) the next day, and (3) the fifth day (hopefully no dex). Results are here.

I didn't like that much dex for several reasons, and when I showed the shart to Dr. L she reduced my dex dosage from 40 mg to 20 mg. This week I did the measurements again for "dex day," and found the glucose levels significantly lower, as expected.

Here are averages for each of three different days:

Dex		Glucose mg/dL
40 mg		144.3
20 mg		115.8
None		88.2

Bottom line: 20 mg of dex puts the average glucose approximately midway between 40 mg of dex and no dex. Huh - no surprise.

Here is a TABLE showing actual measurements and times.

Below is a chart. Click to enlarge.

CC-4047 Study at Ten Weeks

Yesterday morning I had the blood draw for ten weeks in the trial of the new drug CC-4047. Here is a table showing several CBC values on four different dates including yesterday:

	SMG	Mayo	Mayo	SMG
CBC	Mar 28	Apr 03	May 01	May 15	Minimum
WBC (leukocytes) K/uL	5.3	7.7	6.0	4.9	2.0
NE# (neutrophils) K/uL	2.6	4.98	3.26	1.7	1.0
PLT (platelets) K/uL	232	303	243	251	50
RBC (erythrocytes) K/uL	4.54	4.42	3.95	4.32
HGB (hemoglobin) K/uL	15.0	15.1	13.5	14.4

SMG = Stillwater Medical Group in Stillwater, MN
Mayo = Mayo Clinic in Rochester, MN

Dr. L at Mayo is especially interested in the top three counts. If the CC-4047 trial drug causes any of those three to fall below its displayed minimum, the protocol will be changed for me, or, eventually, I could even be dropped from the study. Leukocytes are down a bit and neutrophils are down more, actually below the reference range, but both are still within the normal range of fluctuation observed over the past five years. Good.

I am also interested in the other two. RBC and HGB are always near the low edge of the range for me, and in fact RBC is still below the reference range. But it is up slightly, so my non-medical opinion is that it is stable too. Good.

I left out one set of numbers, taken April 18 at Stillwater Medical Group (SMG). Those showed a lower value for WBC than I have ever had in the last five years, and higher values for RBC and HGB than I have had. My local Dr. L at SMG seems to agree that those are NOT my numbers; there was a mixup somewhere. He is also concerned about the OTHER person, who may have gotten MY results, which probably would have shown a sudden movement in the direction of anemia but no problem with the white counts.

Bottom line: Never make an important treatment decision based solely on ONE set of labs, especially if those labs are inconsistent with other recent ones.



Lunch of leftovers: Hearty chicken soup with free-range chicken, organic carrots, organic peas and more; organic brown rice pasta with organic corn, organic tomato and more; free-range bison with onions and organic carrots.

CC-4047 Rocks!

In early March I joined a phase-2 trial (Mayo Clinic study) of Celgene's new IMiD drug CC-4047, with once-weekly dexamethasone. My two primary markers, IgG and M-spike, are both down almost 50% after just two one-month cycles. This is an excellent response, especially considering that I stopped responding to thalidomide, a similar IMiD. Another patient that I know had an even better response on the same study, with markers dropping by half in just the first cycle. I have heard that other patients have done well too.

CC-4047 is not a cure for myeloma, but it may become a very important tool in managing it and, I'm sure, a lifesaver for some who have exhausted other options. I hope that Celgene will do whatever it takes to get it approved soon - people's lives are on the line.

CC-4047 side effects for me:

• Bradycardia - my resting heart rate has dropped from about 48 to about 41.
• Slight reduction in red cell count and hemoglobin, taking RBC just below the reference range.
• Tinnitus from the aspirin that I take with the CC-4047.

No neuropathy, thromboses, leukopenia, neutropenia, or other difficult side effects yet, though these are all possible. Albumin seems low, but other liver markers are normal.

Dexamethasone side effects:

• "Peppy" and not-so-peppy days, fitful sleep one or two days a week.
• Increase in belly fat - I'm pretty sure this is happening.
• Loss of muscle mass, especially quads - my running speed is declining.
• High blood sugar levels on "dex day," as measured with glucose monitor.
• Dex voice (tight).

Considering the good response and the dex side effects, Dr. L has changed the dex dosage from 40 mg to 20 mg once weekly. And the study continues, now well into the first week of the third cycle.

I'm lucky, or blessed, in so many ways. Most important, myeloma has not yet hurt me. Aside from painless lesions inside three bones, I have no symptoms from the disease itself, and symptoms from the treatment are quite modest thus far. I wish that all myeloma survivors were so lucky, or blessed. Thank you for your prayers, and I offer you mine.

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."

Free-range no-hormone no-antibiotic chicken, organic chard with dried cranberries, macadamia nuts, organic apple, organic pomegranate juice.

Lucky Don

If you skip over the fact of the cancer, I'm a very fortunate guy. The CC-4047 trial is so far very successful for me. After the first one-month cycle, IgG dropped from 2960 to 2230, and after the second cycle it is now 1610. Similarly, M-spike dropped from 2.7 to 1.9, and now to 1.4. This brings my markers back two to three years in just two months.

Best of all, side effects have been quite modest so far, the worst coming from the dexamethasone, not the CC-4047. The regimen will continue for another cycle, probably many cycles, but at half the dose of dex.

I am VERY happy!. Time for celebration. Much more to say about the results and my conversation with Dr. L, but no time to post it tonight. Big weekend coming, so it may be next week before I can bring it all together.

Drug Study at Six Weeks

This morning was the end of six weeks in the trial of the new drug CC-4047. Here is a table showing several CBC values on four different dates including today:

	SMG	SMG	Mayo	SMG
CBC	Mar 21	Mar 28	Apr 03	Apr 18	Minimum
WBC (leukocytes) K/uL	5.8	5.3	7.7	3.6	2.0
NE# (neutrophils) K/uL	2.9	2.6	5.0	1.8	1.0
PLT (platelets) K/uL	245	232	303	148	50
RBC (erythrocytes) K/uL	4.28	4.54	4.42	5.52
HGB (hemoglobin) K/uL	14.3	15.0	15.1	18.5
Albumin g/dL			3.4	3.5

The top three counts are ones that Mayo is particularly interested in watching, because the CC-4047 trial drug may eventually drive those numbers down. If any of those three counts falls below its minimum, the protocol will be changed for me, or, eventually, I could even be dropped from the study. Sorry to say, every one of those counts has dropped dramatically in just two weeks, though they are all still well above their minimum values.

I am also interested in the other three. HGB (hemoglobin) is slightly out of the top of its range. I don't know what to make of that. In fact, both HGB and RBC (red cell count) are higher than I have ever seen them in five years of tabulating results. They're nothing to worry about, but they don't seem like my blood. I'm actually wondering about a lab error.

Albumin, on the other hand, is almost exactly what it was two weeks ago at Mayo, and it is at the lowest I have seen in the five years. More to discuss with Dr. Lacy in a couple of weeks, when we will do the tests again. Albumin is one of the liver-function indicators, and is right on the boundary where the International Staging System would place a newly-diagnosed patient in Stage II rather than Stage I.

Bottom line: Albumin makes sense, though I don't like it much. The others seem wacko for me. I do believe that the albumin blood was drawn into a different tube than the CBC blood, so there is the possibility of a lab mixup in one and not the other. I sort of hope so.



Recent salad: Organic romaine lettuce with cucumber, organic dried sour cherries, blue cheese, salted pistachios, clementine, organic red wine vinegar.

Results of Cycle 1

Today was my 28-day (first cycle) checkup at Mayo for the phase II trial of CC-4047 with dexamethasone. The idea is to make sure that the drugs are not hurting me, though it would also be nice if they were already helping.

Dr. Lacy was away at a conference so I saw Dr. Buadi, another very likeable and knowledgeable doctor.

All of the closely-watched markers of possible harm from the drugs are normal. Yay! Further, IgG was down 25% and M-spike was down 30% in just 28 days. That is very good. The only significant “bad” news was a decrease in albumin, down to the very bottom edge of the reference range, though just within it. I didn't have a chance to discuss this with the doctor today, but I will call tomorrow. Actual values from key tests are displayed graphically in charts and numerically in a test result table, see links below.

I am still on the trial drug and would have started the second 28-day cycle Friday night. However, I am going to stop for two days and start that cycle on Sunday night instead, so that I will not be feeling the effects of dexamethasone on the weekends when I race.
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."

I was still hungry after dinner tonight - this fixed it. Watermelon, blueberries, organic apple, pineapple, organic yogurt, Dove dark chocolate Easter egg.