US 52 Was Under Water

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

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

IgG versus M-Spike:

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

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

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

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

Carfilzomib:

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

Velcade:

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

Some current test results:

Test		Jun 29		Jul 29		Aug 24		Sep 23		Remarks
M-spike g/dL		1.0		1.1		1.1		1.2		Best tumor measure?
IgG mg/dL		1120		1160		1100		1070		Best tumor measure?
L FLC mg/dL		1.74		1.86		2.79		2.58		L Free light chains
Calcium mg/dL		9.9		9.9		10.1		10.0		Below 10.2 is OK
Creat mg/dL		1.2		1.0		1.3		0.9		Kidney, OK
HGB g/dL		14.5		14.0		15.7		15.8		Hemoglobin, OK
RBC M/uL		4.30		4.16		4.39		4.43		Red cells, OK
WBC K/uL		3.4		2.8		4.4		4.2		White cells, OK
ANC K/uL		1.09		0.93		1.41		1.60		Neutrophils, low

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		Somewhat technical. Best with a wide browser window.
My Supplement Regimen		With links to where I buy them.

Innovative Treatment for Relapsed and Newly-Diagnosed Myeloma

Friday night I attended a satellite session hosted by Celgene, the makers of Revlimid and other drugs. Dr David H Vesole, of Hackensack University Medical Center, focused on the newest treatments for myeloma. He said that the two most important tools are Revlimid and Velcade (and he might as well have included dexamethasone (DEX) because it is almost always combined with Revlimid and Velcade).

The new kid on the block is all three, termed VRD. In one study it produced a response in 100% of patients, and a very good partial response (VGPR) or better in 75%. That's pretty amazing. Unfortunately, though, 15% of patients experienced severe neuropathy. Other studies suggest that low-dose DEX may work as well, and with once-weekly Velcade instead of twice-weekly, neuropathy may be reduced to a much smaller number of patients. Continued maintenance with Revlimid improves the result.

Potential newer kids on the block:

• Carfilzomib: This is a "proteazome inhibitor" (interferes with the cell's ability to dispose of waste) like Velcade. Carfilzomib seemed to be on a fast track, but is back in phase I trials to zero in on the maximum tolerable dosage. At lower dosages it appears as effective as Velcade but with only 1% of patients experiencing severe neuropathy. At the higher dosages it may be even more effective, but neuropathy may be increased. I spoke to one person in the sales booth who thought it was still a year and a half away from FDA approval.
• Pomalidomide: I have been on a Phase II study of pomalidomide for 30 cycles. It's an immunomodulatory drug (IMiD) with the capacity to suppress parts of the immune system, particularly myeloma cells, which are wayward plasma cells. Dr Lacy from Mayo Clinic will be presenting a talk which shows a 49% objective response rate even among patients for whom Revlimid and Velcade (both) are no longer effective. I don't know when this drug will be approved - it seems to be on a slow track, and I wonder (lacking specific knowledge) if Celgene has sufficient incentive to hurry this better drug to market as long as Revlimid is making them so much money.

Unanswered questions according to Dr Vesole:

• Should patients be pushed toward a complete response (CR) when a good response is already obtained? Studies do suggest that they do better.
• Is a four-drug combination better than three? The jury is still out, and one study says that they are only equal.
• What do we do when a patient on a three-drug combination relapses?

Actual sign on a Montana interstate:

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.

Even Better News, Probably

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

Results:

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

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

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

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

Related links:

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

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

Here are a few specific test results:

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

Doctor:

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

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

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

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

The end. For now.



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

Good News 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!