Mayo Clinic Cycle 22, Still Stable

I've had trouble sitting down to write this post. The Mayo visit was November 12, almost two weeks ago. Plenty to say, but everything else intervenes, and I STILL don't have all the leaves picked up off the lawn.

Test Results:

At the end of Cycle 22 of the Mayo Clinic trial of pomalidomide with dexamethasone (DEX), no change in M-spike. Still 0.9 g/dL, which isn't bad. In fact the lab said it was 0.86 (verbal), but they round up for the written report because the test really isn't accurate enough to support two digits past the decimal. M-spike has hovered between 1.1 and 0.8 g/dL since June of 2008. IgG is up a little, but Lambda free light chains are down a little and the K/L ratio is up (good). Stable!

Calcium is back where it should be, and none of the other tests raise any eyebrows. Enough about test results.

Ashwagandha:

I've taken 225 mg of Sensoril brand ashwagandha every evening for the entire cycle. With no discernible change in test results, it's hard to say that the ashwaghanda has done anything, except help with a good night's sleep. Maybe I should double the dose. Instead, though, I'm now taking the pomalidomide at night, with the ashwagandha, rather than in the morning. That may make a difference, maybe not.

Peripheral Neuropathy:

Some months ago, after 15 cycles of pomalidomide, I noticed some numbness in the soles of my feet and a little tingling in my thumbs. No pain. I immediately did some research and started a new treatment for it, and the neuropathy stabilized. It hasn't changed much now in several months. I do not know whether my treatment is helping to stabilize it, because I haven't stopped the treatment to find out, but for what it's worth, here it is:

Daily dosage:

A good daily vitamin
A good multi-B vitamin
Vitamin B6	100		mg
Vitamin B12 sublingual	1000		mcg
Vitamin E	200		mg
Alpha Lipoic Acid	1200		mg
L-Carnitine	1000		mg
Bromelain	1000		mg
Flax Seed Oil	2000		mg
Curcumin	500		mg

Where it's necessary to take more than one capsule or tablet, I divide the dosage in two, taking half with breakfast and half with dinner.

I also believe in keeping the "peripherals" warm, because healing works far better when tissue is at body temperature. I wear wool socks most of the time, even in bed, and cotton gloves in bed. In addition, we eat very well (nothing that doesn't contribute to health), and get good exercise.

Things that are recommended (somewhere) but which I do not yet do:

• Topical emollient creams, with cocoa butter and spearmint, menthol, or even capsaicin, to stimulate nerves.
• Evening primrose oil supplement.
• "Magnesium Oil."
• L-Glutamine, up to 30 grams daily. I have it on hand, just don't find it convenient to take it.
• Pickle juice can work for cramps, maybe for neuropathy? One friend swears by it.
• Acupuncture.
• Transcutaneous electrical nerve stimulation (TENS). May have a temporary benefit.
• I don't smoke, but if I did I should stop! Duh.
• Biofeedback.
• Infrared heat.
• There are various gizmos and treatments advertised on the web. Buyer beware.

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."

Some current test results:

Test		Aug 20		Sep 17		Oct 15		Nov 12		Remarks
M-spike g/dL		0.8		0.9		0.9		0.9		Best tumor measure
IgG mg/dL		979		1070		1020		1100		Variation is normal
L FLC mg/dL		2.07		2.54		2.68		2.61		L Free light chains
Calcium mg/dL		9.7		10.0		10.3		9.8		Below 10.2 is best
Creat mg/dL		1.1		1.0		1.0		1.0		Kidney, lower is better
HGB g/dL		14.8		14.5		15.0		14.4		Hemoglobin, normal
RBC M/uL		4.13		4.01		4.21		4.00		Red cell count, low
WBC K/uL		3.9		3.7		4.2		3.9		White cells, normal

Discussion with Dr. L:

• She finished a recent marathon in a very nice time, despite having to wear a lot of clothing to keep warm.
• She thinks that my running inspires hers. As for me, I'm very proud of her.
• In answer to my question, yes, get a pneumonia shot.
• If ashwagandha didn't help in the first month, maybe in another month.
• There is a study of an oral form of Velcade.
• There is also a study of a drug currently in use for renal cancer.
• The pomalidomide trial is now open for people who have failed both Revlimid and Velcade.

American Society of Hematology (ASH):

Apparently it is unusual for a myelomiac to be able to run marathons. Thus far I have been lucky enough to avoid broken bones, and I've done eight marathons this year. The International Myeloma Foundation (IMF) has invited me to attend the annual ASH Conference, December 4-7, as an advocate for new treatments like pomalidomide. I will try to blog about it in real time, and will certainly report on it afterward.

Don finishing the OBX Marathon November 8

Ashwagandha

Mayo Clinic Visit Thursday, October 15, 2009, end of Cycle 21

Blood test results: M-Spike remained the same at 0.9 g/dL, IgG dropped slightly from 1070 to 1020 mg/dL, and Lambda light chains increased slightly from 2.54 to 2.68 mg/dL. These results don't really show a trend one way or another. "Stable" is the word.

Except: calcium is up from 9.9 to 10.3 mg/dL, above the reference range, and we don't know why. High calcium in the blood can indicate that bone damage is occurring. It went that high once before, though, and dropped right back down a month later. Hopefully next month's value will be back within range. I will skip my calcium supplements for a day or two before next month's tests, in case that makes a difference.

Of course I'm still concerned about the longer term, when the Phase II trial of pomalidomide with dexamethasone (DEX) eventually fails for me and a different, less-agreeable treatment will be required. Two months ago we reduced my DEX dosage from 8 to 4 mg once weekly - perhaps that was a mistake. Unfortunately, though, under the terms of the study, DEX can only be decreased and never increased, so if I want to continue taking pomalidomide I will continue taking 4 mg or less of DEX. Pomalidomide is good stuff - I DO want to continue on it for as long as possible.

Ashwagandha:

The study doesn't say much about supplements. Margaret has recently blogged about ashwagandha, also called "withania somnifera," a shrub from India and nearby countries. The root is widely used as a medication in that region, and in alternative medicine in other parts of the world. Margaret took ashwagandha herself, and saw her IgG drop 25% and M-Spike drop 10% over a period of several months. She has written several posts about ashwagandha, all worth reading. Because of her apparent success, I have begun taking ashwagandha in a modest dosage. I ordered the patented Sensoril brand, packaged in capsules by Jarrow. I take one 225-mg capsule daily, the amount suggested on the bottle, at bedtime because it also induces a restful sleep.

In addition, I have added 100 mg of ordinary vitamin B6 to my regimen as an additional treatment for the mild neuropathy that is induced by the pomalidomide, and doubled the supplements for thyroid. The entire daily supplement regimen is available from a link in the right-hand panel.

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 wiiide browser window. Very "technical."

Some recent test results:

Test		Jul 23		Aug 20		Sep 17		Oct 15		Remarks
M-spike g/dL		0.8		0.8		0.9		0.9		Best tumor measure
IgG mg/dL		1010		979		1070		1020		Variation is normal
L FLC mg/dL		1.95		2.07		2.54		2.68		L Free light chains
Calcium mg/dL		9.6		9.7		10.0		10.3		Below 10.2 is best
Creat mg/dL		1.0		1.1		1.0		1.0		Kidney, lower is better
HGB g/dL		14.0		14.8		14.5		15.0		Hemoglobin, normal
RBC M/uL		3.93		4.13		4.01		4.21		Red cell count, low
WBC K/uL		5.6		3.9		3.7		4.2		White cells, normal

Discussion with Dr. KDS:

Don:

• Peripheral neuropathy from the pomalidomide has not changed much in this cycle. Still some numbness in the bottoms of my feet and in my thumbs. There is also a little tingling but no pain. The "tickle" sensation in my feet, sensitivity to light touch, might actually have improved somewhat, but the sensitivity to pressure has definitely not improved.
• Many myelomiacs get shingles, because of compromised immune systems. I'd rather not, thank you. So I asked Dr. KDS about the shingles vaccine:
  • It is a live-virus vaccine, and not recommended for people who are immunocompromised; but
  • I don't get sick much - no empirical evidence that my immune system actually IS compromised, but
  • She pointed out that IgA, IgG, and IgM are important parts of the immune system, and in my case both IgA & IgM are at very low levels;
  • Further, if we subtract the monoclonal (worthless) M-Spike component of IgG from the total IgG, the remaining "good" IgG is also well below normal; so
  • I guess I really do have a compromised immune system. Not enough immunoglobulin goblins. **
  • Dr. KDS knows of a case where an immuno-compromised patient actually DID get shingles from the vaccine. Ouch.
  • I suggested using the killed-virus chicken-pox vaccine off-label as a shingles vaccine, but don't recall her response. It wasn't positive.

KDS on flu vaccines for myelomiacs, same advice as last month:

• Get the 2009 H1N1 vaccine as soon as it is available to me. I am not in one of the highest-priority groups.
• Get the seasonal flu vaccine when it is available to me.

Don's thoughts on flu vaccines for myelomiacs (Dr. KDS is not implicated in the following content :-)):

• Seasonal Vaccine:
  • So far, the CDC is not seeing much seasonal flu. In their latest report, almost all of the viruse samples submitted to them in the week Oct 4-10 were found to be 2009 H1N1.
  • Therefore, we need not rush to get the seasonal vaccine, because there isn't much risk of encountering the virus yet. However:
    • The seasonal flu is at least as deadly as 2009 H1N1;
    • Tens of thousands of people DIE from it every year in the USA alone; and
    • Those of us with compromised immune systems are especially at risk; so
    • We definitely should get it well before the seasonal flu peak arrives. The past three seasons saw minor peaks around Christmas with the major peak in February.
• 2009 H1N1 Vaccine:
  • Availability may be spotty because of the priority system, which is applied differently in different places.
  • Get it as soon as it is available, because the VIRUS IS AMONG US! Rampant in some schools.
  • In the meantime, we might be well advised to stay away from groups of people, especially young people.
  • Some doctors say that the vaccine might not do much good anyway, because compromised immune systems can't muster a proper response, but
  • To me that sounds like an excuse and not a reason. If it "might not" do much good then it also "might" do some good, and that's enough for me.
  • That same excuse could be used for skipping the seasonal flu vaccine, and no doctor suggests that.
  • I have not heard of any downside of the H1N1 vaccine, other than the rare problems that can occur with any flu vaccine. If you have heard otherwise, please comment.

We three have some airplane flights coming up, and have even talked about wearing medical masks in that wheezy, sneezy, huddled mass of humanity. We'll see!

** Halloween humor

---

Salad as dinner.

IMF Patient & Family Seminar

Friday, August 28, and Saturday, August 29:

The International Myeloma Foundation (IMF) Patient & Family Seminar was interesting and information-packed, to say the least. We heard doctors from all around the country discuss topics like Ask the Expert, Managing Side Effects, Frontline Therapy, Role of Transplant, Bone Disease, and Approaches to Relapse. I think that about 100 of us myelomiacs attended, many with their caregivers. I've been dealing with myeloma for six years now, so a lot of the information was not new, but here are a few things that I learned, or perhaps re-learned:

Transplants:

• It appears to make little difference in overall time of survival whether the transplant is done early or late, as long as stem cells are collected early before the bone marrow gets all beat up. A current Dana-Farber trial may clarify this further.
• More transplants are done for myeloma than for any other disease.
• The mortality rate for a single autologous transplant is less than 1%.
• Revlimid can decrease the yield of a later stem-cell collection.
• Medicare wil pay for one transplant up to age 76.

New Treatments & Tests:

• Three- and four-drug combinations can produce very good initial responses, but it's not yet clear what happens if and when the combo fails. Will the individual drugs have any impact then?
• Carfilzomib, the new proteazome inhibitor, is much less apt to cause neuropathy than is Velcade. Currently available only in trials.
• Denosumab is a new monoclonal antibody with the potential to help treat osteoporosis and repair bone damage. It may replace Aredia and Zometa in some cases. Currently available only in trials.
• Pomalidomide, the new thalidomide analogue, is succeeding in its Phase II trial and is now scheduled for a Phase III trial in 2010. Only available in trials.
• A new "power needle" for bone marrow biopsies has been approved by the FDA. When manufacturing problems are overcome and it becomes available, it will make biopsies quicker and less bothersome.

Bone:

• Myeloma causes bone damage in about 80% of patients, but not in the other 20%. This is unrelated to the aggressiveness of the myeloma. As it happened, a survey of attendees showed that 80% of us had bone disease.
• Aredia and Zometa can eventually saturate the bones with bisphosphonate, and the half-life is 10 years, so therapy should be cut way back.
• There is a risk of necrosis of the hip joint, and perhaps other joints, with prolonged dexamethasone use, especially with concurrent bisphosphonates. This is a serious problem if it occurs. The risk of occurrence is low, but I'm thinking I've maybe had about enough DEX.

Other Stuff:

• Mayo Clinic in Arizona still uses high-dose dexamethasone with Revlimid or Velcade for the first two cycles, to get a rapid response. Often a rapid response is important for patients who have recurring disease.
• Neuropathy from Velcade may be painful, whereas neuropathy from thalidomide or Revlimid is more likely to present as numbness.
• Velcade neuropathy is likely to improve if treatment stops, though, whereas neuropathy from thalidomide usually does not.
• Ibuprofen can defeat some of the anti-clotting benefit of aspirin. Oops.
• "Hemonc" is short for hematologist/oncologist. Maybe I'll try that at Mayo, see if it flies.
• Diet is important. Dr Durie's advice: (1) Don't eat anything that your grandmother wouldn't recognize, and (2) Shop around the edges of the supermarket.
• There seemed to be a growing consensus that myeloma can be caused by benzene and various pasticides, even herbicides.
• Two attendees reported that they were diagnosed with myeloma shortly after a significant weight loss. Dr Durie pointed out that toxins are stored in body fat, and may flood the body when fat is lost.

Anything that I should add?


Sunday's breakfast. There is oatmeal under there somewhere.

Pomalidomide Is Still Working

Mayo Clinic Visit Thursday, July 23, 2009, end of Cycle 18:

I started on the Mayo Clinic phase-II trial of pomalidomide, then called CC-4047, almost a year and a half ago. My M-spike, a measurement of proteins from the malignant cells, dropped from 2.7 down to 1.1 g/dL within four 28-day "cycles." Since then it has slid a little more, mostly hovering between 1.0 and 0.9. Today it was 0.8 g/dL. Whoopee! Down is always good. It has been down to 0.8 once before. Dr L put a little smiley face on the results printout, next to M-spike.

So is this a real downward change in the M-spike or just a variation in the test itself? M-spike is a notoriously variable test. Well, Immunoglobulin G (IgG) is exactly the same as it was 28 days ago, 1010 mg/dL. Since IgG and M-spike tend to track each other, perhaps the decrease in M-spike is false. On the other hand, Lambda light chains dropped 26% to 1.95 mg/dL, by far the lowest I've seen in six years of living with myeloma. This is another erratic test, but it appears to be valid because Kappa light chains are unchanged. Most of the Lambda light chains come from the malignant cells, so perhaps the decrease in M-spike is real.

Whatever. One can analyze these things way too much. Better to celebrate a little, because for sure M-spike didn't go UP, and then wait 28 days for the next result.

Peripheral neuropathy (PN) is still an issue. Mine is still mild, with some partially-dead spots and some tingling in the bottoms of my feet and one thumb. Happily, it seems to be stable, not getting worse any more. I'm putting together another post on neuropathy and hope to publish it 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. Add peripheral neuropathy to the list.

Here are a few of the latest test results:

Test		Apr 30		May 28		Jun 25		Jul 23		Remarks
M-spike g/dL		0.8		0.9		0.9		0.8		Best tumor measure
IgG mg/dL		1060		1030		1010		1010		Variation is normal
L FLC mg/dL		2.55		2.60		2.63		1.95		L Free light chains
Calcium mg/dL		9.6		10.0		9.6		9.7		Below 10.2 is best
Creat mg/dL		0.9		1.0		1.0		1.1		Kidney, lower is better
HGB g/dL		14.3		14.4		14.0		14.8		Hemoglobin, normal
RBC M/uL		4.01		4.06		3.93		4.13		Red cell count, low
WBC K/uL		3.6		4.0		5.6		3.9		White cells, normal

Doctor:

Sunshine and I also discussed with Dr L:

• I told her that because of the muscle wasting and other side effects I wanted to reduce the DEX dosage, currently 8 mg, but because the trial doesn't allow the DEX to be increased again I would refrain from proposing that. Her response led me to believe that the DEX, now at only 8 mg once per week, may not be doing that much good anyway, and we should revisit the issue in another month. I'm up for that.
• I mentioned that I had gained a few pounds since the beginning of the trial, but that because of the muscle wasting from DEX my body had changed shape, with a layer of fat on my belly and chest. I told her that I had gone back on Weight Watchers to get the weight under control, and re-started a resistance training program to try to reverse the muscle wasting. She approved.
• I mentioned that I had recently done a difficult run with a heart rate monitor, which reported an average rate of 126 and a maximum of 142 beats/min. These numbers are perhaps ten beats/min lower than they should be. I mentioned that I had looked back at similar records while I was on thalidomide, in 2004 and 2007, and seen similar reductions in exercise heart rates. She acknowledged this and said that it happens with Revlimid as well.
• She asked if I felt tired, noting that I had apparently said I was tired in a checkup last December. I said no, I wasn't any more tired than a 68-year-old should be, and certainly not chronically tired. I can just see the doctor's writeup: "patient denies feeling tired." :-)
• We discussed peripheral neuropathy. I've accommodated to it somewhat, as it seems to have reached a stable level, with some tingling and partial loss of feeling in my feet, not getting any worse. I mentioned that I am taking the full regimen of supplements and also keeping my feet warm, as I believe that warmth aids healing. She said that she also believes that stimulation helps, and suggested massage as well.
• For 17 cycles I took the pomalidomide at bedtime and, on DEX days, took the DEX with dinner. For this past cycle I took the pomalidomide before breakfast and the DEX with breakfast. I mentioned that I preferred taking the DEX in the evening, and she didn't think it would make much difference. Indeed, the change to morning meds didn't seem to make much difference in this past cycle, though it certainly didn't hurt either.
• She said a few things about pomalidomide that I won't report because they are not yet published, but I think these are OK and I hope I got them right:
  • 82% of trial patients got at least a 25% reduction in M-spike.
  • About the same percentage of patients have responded to pomalidomide as respond to Revlimid, but many of these have previously failed Revlimid.
  • Patients with high-risk genetics are experiencing encouraging responses.
  • One patient in particular did not respond for six months, and then the M-spike dropped very dramatically.
  • Other patients have reached a plateau, level for several cycles, followed by a gradual drop to still-lower numbers.
  • Her theory as I understood it: Pomalidomide first reduces the tumor burden directly by interfering with NF-kB and possibly by other mechanisms as well. Then the body's own immune system is able to continue the good work and improve on it.
  • She said that malignant cells pop up within each of our bodies all of the time, but our immune systems normally spot those and kill them.
  • Some patients reach a plateau, as I have, and then just stay there, as patients sometimes do on Revlimid. I hope that's me - she hopes so too.
• I showed Dr L a chart of blood glucose versus time of day (below), with DEX taken at breakfast. She remarked that it didn't seem too bad, meaning that the glucose never went too high, even at meals. I mentioned that we do try to minimize carbohydrates on DEX day, and she said that was a good idea.

Other Stuff:

As part of the study I get an electrocardiogram (ECG) every three cycles. This time the cardiologist reported "marked sinus bradycardia with sinus arrhythmia." Bradycardia is simply a low heart rate - mine was 38 this time, the lowest ever. No surprise, though, I'm a runner with an endurance athlete's heart, and with the added effect of the pomalidomide I always get a comment about bradycardia. I don't recall getting a comment about "sinus arrhythmia" before, but as far as I can tell that just means that the interval between beats is not perfectly regular. Dr L didn't bother to comment on it.

For the upcoming cycle I plan to take the pomalidomide in the morning, usually before breakfast, and the DEX Sunday evening with dinner.

Also, one of the people who post on the MMA List recently noted that alcohol is a neurotoxin, and said that his neuropathy improved when he stopped having his evening glass of wine. It's worth a try, so I may also find an appropriate window of days and stop enjoying my one evening beer for at least a week, just to see if there is any improvement. Sigh.


Chart of blood glucose versus time, after 8 mg DEX taken with breakfast. You can see the spikes caused by lunch and dinner. Glucose was normal by the next morning, so that effect of the DEX seems to clear within about 24 hours.

Stable Is Good

Mayo Clinic Visit Thursday, June 25, 2009, end of Cycle 17:

According to Mayo, CC-4047 is now officially called pomalidomide, which is the generic name, like lenalidomide is for Revlimid. There is no trademark name yet, like "Revlimid," though "Actimid" was used for a while and then apparently discarded because of its similarity to Actifed. Don't want to mix THOSE up. I'll probably use pomalidomide and CC-4047 interchangeably here - we'll see.

I just got the results for Cycle 17 of the Mayo Clinic phase-II study of pomalidomide with dexamethasone. Bottom line: No change from 28 days ago. Dr KDS pronounced it "stable." M-Spike is 0.9 g/dL, unchanged, and IgG is 1010, virtually unchanged from 1030 mg/dL. Other results are mostly the same as well, except white blood count and neutrophils are up 40% and 60%, respectively, probably because I'm battling a cold.

Peripheral neuropathy (PN) is still the issue. Turns out that pomalidomide can cause PN just as Revlimid can. Mine is still mild, with some partially-dead spots and some tingling in the bottoms of my feet and one thumb. It doesn't seem to be getting worse very fast, but it is the fly in the chicken soup. I'm putting together another post on neuropathy (as if I know anything about it) and hope to publish it 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. Add peripheral neuropathy to the list.

Here are a few of the latest test results:

Test		Apr 02		Apr 30		May 28		Jun 25		Remarks
M-spike g/dL		0.9		0.8		0.9		0.9		Best tumor measure
IgG mg/dL		1060		1060		1030		1010		Variation is normal
L FLC mg/dL		3.04		2.55		2.60		2.63		Free light chains
Calcium mg/dL		9.5		9.6		10.0		9.6		Below 10.2 is best
Creat mg/dL		1.0		0.9		1.0		1.0		Kidney, lower is better
HGB g/dL		14.7		14.3		14.4		14.0		Hemoglobin, normal
RBC M/uL		4.26		4.01		4.06		3.93		Red cell count, low
WBC K/uL		4.2		3.6		4.0		5.6		White cells, normal

Doctor:

Sunshine and I also discussed with Dr KDS:

• PN from pomalidomide is probably not like the mostly-permanent PN from thalidomide. There is not a lot of experience with it yet, actually, but when a patient goes to a 21-day-on and 7-day-off regimen it often gets better during the seven days. Further, it may reach a mild level, as mine has, and then not progress further. Or it may continue to get worse.
• It may or may not reverse fully when the patient goes off pomalidomide altogether.
• Mayo uses the following classification system for PN (if I heard this right):
  • Grade 1 = Mild tingling or numbness or abnormal nerve-function tests (me).
  • Grade 2 = Some interference with function, but not disabling. E.g. little or no feeling in some fingers.
  • Grade 3 = Some disability, e.g. difficulty driving or operating other equipment.
  • Grade 4 = Major disability, e.g. wheelchair required.
• For most patients on pomalidomide who get PN, it remains at Grade 1. But the study is young.
• Running doesn't seem to make a difference for me. I ran three marathons during the 28-day cycle, and the neuropathy did not get worse after any of them. It may have gotten slightly better, though not much.
• I believe that warmth is a key to healing, and mentioned that I keep my feet warm as much as possible, using wool socks much of the time, even in bed. She agreed, and said that other patients have stated that their PN gets worse when their feet are cold. This may not cause irreversible PN, but perhaps it has a cumulative effect. No clogs for me.
• I asked if neuropathy can ever extend to the male sex organs. She replied, with some definiteness, that it can. On further discussion, however, it seems the effect is loss of function, and may not be from neuropathy per se but from the myeloma and its treatments. Perhaps I'll ask Dr L the same question next session. It's important.
• I asked about the most likely course of the myeloma with pomalidomide treatment. She responded that the study is only a year and a half old, so there isn't a lot of information yet, but it has begun to fail for some patients, just as thalidomide and Revlimid usually fail eventually. I joined the study in its first three months, so I'm fortunate that it's still stable for me.
• If Revlimid is a model for pomalidomide, a few patients may remain stable on it for years. Oh, I hope I'm one of the few. We shall see.
• I'm scheduled for a very warm marathon in a few weeks, so I asked if the myeloma or its treatments put me at any more risk than any other 68-year old. She thought not, but couldn't resist advising me to be careful. Heck, if I'm careful, I won't do it. And I might not.

Other Stuff:

Going off grapefruit for a month didn't seem to change the M-Spike, and the PN got a little worse even without it, so I'm going back to enjoying a grapefruit every day.

I have the longest-lasting cold I've had in years, almost three weeks now. Maybe I was just due for a major cold, or maybe my immune system is impaired by the DEX and three successive marathons. It's getting better though. Perhaps the grapefruit will help.

My regimen will not change in the next cycle. If the PN gets significantly worse, I will call the doctor.



At least four chicks hid in this robin's nest about five feet off the ground. Mama was yelling at me as I took this photo, threatening me with close fly-bys. The next day all of the chicks left the nest - I saw one of them go. Mama took them farther into the woods, yelling all the while.

Neuropathy is the Issue

Mayo Clinic Visit Thursday, May 28, 2009, end of Cycle 16:

Peripheral Neuropathy:

I posted about the possible beginnings of peripheral neuropathy (PN) eleven days ago. In those days I have taken most of the supplements listed on my Supplement Regimen page. The symptoms have not disappeared, however, though they have changed a little, and I am still not certain (beyond a reasonable doubt) that the feelings in my thumbs and feet are in fact PN from the CC-4047 medication.

There is normal sensation, or I should say no sensation, from the affected areas unless they touch something. One thumb always feels fine now, and the other, which was injured and its nerves cut many years ago, does tingle when touched, though the thumb pad is still sensitive to touch in the normal way as well. The soles of both feet also feel tingly when I walk on them, the same sort of tingle that one may feel when a limb is waking up after being "asleep" for lack of blood. Like the thumb, though, the skin of the soles of the feet is still normally sensitive to touch, and in fact the soles of the feet are still ticklish. None of this affects my running yet, nor is it really even very annoying. Yet.

Bottom line: if this is PN, it isn't very bad yet. I discussed all of this with Dr KDS at Mayo today. She advised me to keep them posted if the PN advances at all, because there are things that they can do. She talked about a few prescription medications, such as Neurontin, for managing the symptoms of PN. She did not, however, hold out any hope of a drug that would reverse the PN itself. She also mentioned that one patient had obtained good results from a machine of some sort, and will get me more information on that. When she does, if it's real, I'll post whatever I can about it.

Test Results:

I'm still on the trial of CC-4047 with dexamethasone (DEX), now taking CC-4047 2 mg every day and DEX 8 mg every Sunday night. In the past 28-day cycle IgG has gone from 1060 to 1030 mg/dL, Lambda free light chains from 2.55 to 2.60 mg/dL, and M-Spike from 0.8 to 0.9. Basically, this is no observable change, because each change is well within the measurement error of its test. Everything else is good too - calcium is up but well within range, ALT and AST are down, LDH is actually below its reference range at 130 U/L, WBC and ANC were down a bit last month but are now back up, it's all cool.

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. Add peripheral neuropathy to the list.

Here are a few specific test results:

Test		Mar 04		Apr 02		Apr 30		May 28		Remarks
M-spike g/dL		0.9		0.9		0.8		0.9		Best tumor measure
IgG mg/dL		923		1060		1060		1030		Variation is normal
L FLC mg/dL		2.64		3.04		2.55		2.60		Free light chains
Calcium mg/dL		9.7		9.5		9.6		10.0		Below 10.2 is best
Creat mg/dL		1.0		1.0		0.9		1.0		Kidney, lower is better
HGB g/dL		13.7		14.7		14.3		14.4		Hemoglobin, normal
RBC M/uL		3.89		4.26		4.01		4.06		Red cell count, low
WBC K/uL		4.5		4.2		3.6		4.0		White cells, normal

Doctor:

Sunshine and I also discussed with Dr KDS:

• Mayo has seen some patients on CC-4047 develop peripheral neuropathy, as they might with thalidomide or Revlimid. There is not yet enough information to say how likely or how serious this side effect might be.
• Dr KDS is going to ask a dermatologist if there is anything to be done about thinning skin from the DEX.
• She confirmed that the DEX can cause wounds to heal more slowly. It seems to take a month now, instead of a week or two, for a little cut to heal.

Grapefruit:

Since about Christmas I've been eating a grapefruit every day. Grapefruit can increase the potency of some drugs by inhibiting a digestive process that would normally reduce the amount of drug that can go from the stomach into the blood. We have wondered if the grapefruit has played a part in the good M-Spike results in recent months by increasing the concentration of CC-4047 in my blood. Now, of course, we also wonder if it might not increase the severity of peripheral neuropathy symptoms if I'm getting more CC-4047 than expected. Therefore, for the next month, no grapefruit for me. Too bad - I've been looking forward to that daily refreshment.


Organic oatmeal, organic strawberries, organic grapes, mango, banana, organic walnuts, organic nonfat milk.

Peripheral Neuropathy Treatment

It's here, perhaps. Maybe. I hope not. In the past few days I have felt a tingling sensation in the very tips of both thumbs, becoming much stronger when I touch the skin there. Nothing in the fingers yet. But in bed last night I noticed a numbness in the sole of my left foot; not so much the toes as the ball of the foot and nothing in the right foot yet.

That's all so far. Not enough to affirmatively declare that peripheral neuropathy (PN) is upon me, but enough to be a little scared. PN can be very painful and, when body parts go numb, rather disabling as well. It usually begins in the sensory nervous system, but can even progress to the motor nerves, resulting in partial paralysis. It is to be avoided if possible, and in my opinion it should be accepted as a necessary consequence of treatment only if all other avenues of treatment have been exhausted.

In Myeloma patients PN can be caused by at least three different things:

• Myeloma-specific chemo drugs such as thalidomide. I'm not taking thalidomide any more, but am taking CC-4047, a thalidomide derivative.
• Dexamethasone (DEX), which I am taking, and which (I believe) can cause symptoms of diabetes, one of which is PN.
• The myeloma itself, especially if protein or light-chain counts are high. Mine are not, as of two weeks ago.

I have another Mayo appointment in two weeks, when this subject will get some genuine medical attention. Furthermore, by that time, I will have a better idea whether or not I really do have PN.

In the meantime I'm trying to learn about it, and do whatever I can to mitigate the problem. Happily for me, the leaders of the Minneapolis Myeloma Support Group handed out a sheet of information on PN treatment at yesterday's monthly meeting.

Dana-Farber Cancer Institute:

That sheet, it turns out, was a printout of a web page which was transcribed from a paper handout at Dana-Farber. A myeloma survivor (Beth I think) has posted that handout HERE on the website MMSupport.net, which also has lots of other good information about myeloma and treatment. To summarize the sheet:

• Multi-B vitamins with B1, B6, B12, folic acid, and the other B-vitamins. Dosages: B6 100-200 mg, folic acid 1-2 mg.
• Vitamin E 400 IU daily.
• Fish oils with the omega-3 acids EPA and DHA.
• Evening primrose oil capsules.
• Flax seed oil.
• Amino acids. No further description.
• Alpha-lipoic acid (ALA) 200 mg twice daily, within 2 hours of a meal.
• Acetyl L-carnitime 500 mg twice daily, within 2 hours of a meal.

The same page gives advice for cramping, and also has a list of prescription drugs. I get the impression from members of our support group that the best of those drugs come with their own list of significant side effects. On the Dana-Farber.org website itself there is another Q & A page listing non-prescription alternative & nutritional self-treatment for PN. Summary:

• Vitamin B6, 50-100 mg/day.
• L-glutamine, 15 grams twice daily. Find a brand with no fillers.
• Alpha-lipoic acid 300 mg twice daily for up to four weeks, then consult a dietitian or doctor.
• Acupuncture.

MD Anderson Cancer Center:

MD Anderson is currently running a trial of oral alpha-lipoic acid versus a placebo for chemotherapy patients. Further, there is a PDF document on the MDAnderson.org website in which Dr Oh discusses diabetic PN. He suggests vitamin E, vitamin B, and L-acetyl-carnitine (same as acetyl-L-carnitine).

Mayo Clinic:

I didn't find much on the Mayo Clinic web site except for one reference to the use of vitamin B-12 to prevent PN. However, I know that Mayo did a study with intravenous ALA which showed marked improvement for patients with diabetic neuropathy. I just can't find that study right now.

Naturopathic Community:

This is a large community and I haven't done much of a search yet, even though naturopathy may be the best bet for controlling symptoms of PN. The first website I came across suggests B-12, ALA, and L-glutamine, with additional supplements if poor circulation is suspected.

International Myeloma Foundation (IMF):

I found one good video presentation from last December's Myeloma Workshop in Washington DC. Dr Paul Richardson, from Dana-Farber Cancer Institute described research on the cellular mechanisms that appear to cause neuropathy, and gave a quick list of possible complimentary treatments:

• Multi-B vitamin, folic acid, and vitamin E.
• Alpha-lipoic acid, L-carnitine, and L-glutamine.
• Magnesium and potassium.
• A daily multivitamin.
• Topical emollient creams containing cocoa butter with spearmint or menthol. He explained that the injured nerves are in a very thin layer just under the skin and these creams might be able to stimulate them.

Margaret's Corner:

In a recent post, Margaret's Corner, an important source of information regarding myeloma treatments, states that curcumin can help alleviate and possibly reverse peripheral neuropathy from chemotherapy.

Georgia Cancer Treatment Center:

Sunshine found this newsletter which suggests:

• Bromelain 200-400 mg three times daily
• L-glutamine 10 grams three times daily, and
• Vitamin B-complex. It also points out that bromelain is abundant in pineapple, and that it also treats other maladies such as bruising, arthritis, bunions, bursitis, tendonitis, carpal tunnel syndrome, gout, and sinusitis.

A Regimen:

It turns out that I am already taking many of the supplements that are recommended above, though some in lower quantity than recommended. I will modify my supplement regimen so that it includes:

• A daily multivitamin.
• A good multi-B (e.g. B-100), with added B6 if necessary to get 50 to 100 mg/day but not more than 100 mg.
• Vitamin B-12 sublingual 1000 mcg daily.
• Alpha-lipoic acid 300 mg twice daily.
• Acetyl-L-carnitine 500 mg twice daily.
• Vitamin E 400 to 800 IU daily, but not more than 800.
• L-glutamine 15 to 30 grams per day. Wow.
• Curcumin 500 mg daily.
• Flax seed oil 1000 mg per day. Maybe fish oil too, but I need a reliable source.
• Bromelain, amount undetermined just now.

If that doesn't solve the problem, then I'll consider:

• A visit to my naturopath for her advice. Might do that soon anyway.
• Altering the chemo to reduce symptoms, such as three weeks on and one week off instead of the current four-weeks-on regimen. Mayo Clinic will have something to say about this of course - I'm in a trial.
• Acupuncture.
• Evening primrose oil.
• Magnesium and potassium, more than I now get in food and the multivitamin.
• Topical creams with cocoa butter and spearmint or menthol.

Your Turn:

This is a huge subject, barely touched in this blog post. If you have suggestions or information, please do comment. Sometimes the comments are much more helpful than the post itself. Thanks,

Don