[Multibilly]

Re: Fenofibrate (Tricor) and multiple myeloma

by Multibilly on Mon Apr 21, 2014 8:34 pm

Thanks Cheryl,

Yeah, I know that FLCs have a much shorter life than IGs, but I never heard that they were a more sensitive indicator about what is going on with one's overall IGs?

I was at first thinking that maybe it was a Light Chain Escape phenomenon that I'm seeing (but I wouldn't expect my IgG to be dropping at the same time)?

Then again, I also have a relatively strange situation where my serum FLCs don't make it past my kidneys into my urine, so maybe that is part of the mystery....I would have more serum FLCs since my kidneys are rejecting the serum FLCs?? But if that were the case, I would simply expect my serum FLC levels just to be artificially higher, not increasing over time?

In any case, I suspect others have seen this phenomenon where an involved IG goes one way and the companion involved FLC goes the other way?

Or, maybe I'm just over-analyzing some relatively small numbers

[Cheryl G]

Re: Fenofibrate (Tricor) and multiple myeloma

by Cheryl G on Mon Apr 21, 2014 9:11 pm

I should have clarified what I said about free light chains being a more sensitive marker, Multibilly. I meant in regard to the particular involved immunoglobulin -- not all immunoglobulins.

Because your lamba IgG light chains have a lot lower half life than the overall IgG molecule, supposedly you'll see changes in the light chain measures before you see changes in the IgG levels.

Here's a paragraph from the Binding Site website about FLC testing that explains the whole thing:

One particularly interesting aspect of serum FLCs is their short half-life in the blood (κ 2-4 hours, λ 3-6 hours) (Chapter 12.4). This is approximately 100-200 times shorter than the 21-day half-life of IgG molecules. Hence, responses to treatment are seen in “real time”. This is apparent from the good correlation between bone marrow assessment of disease status and FLC concentrations but poor correlation with IgG concentrations [9]Thus, FLC concentrations allow more rapid assessment of the effects of chemotherapy than do monoclonal IgG or IgA concentrations. The impact of this phenomenon is likely to be considerable: for instance, the resistance of patients to particular drugs or drug combinations can be observed quickly and alternative treatments considered. In addition, the short half-lives of FLCs often allow assessment of complete tumour responses after one or two cycles of chemotherapy and before stem cell transplantation.[16] Thus, IgG with its 21-day half life is a slow marker of treatment responses whereas FLC analysis allows more accurate assessments.

http://www.wikilite.com/wiki/index.php/Overview_-_The_clinical_importance_of_serum_free_light_chain_analysis

The more I think about it, the more I realize that there's an assumption behind some of these explanations in that paragraph that isn't made explicit. It's that the free light chains are thrown off near the beginning of an IgG molecule's life cycle. Is that true?

If, instead, light chains are thrown off at a constant rate through the IgG molecule's life cycle, then I don't see why the light chain levels should be a more sensitive measure of what's happening with the overall IgG level.

[Multibilly]

Re: Fenofibrate (Tricor) and multiple myeloma

by Multibilly on Mon Apr 21, 2014 11:00 pm

Thanks for the explanation Cheryl. This is good stuff to understand, especially for those undergoing treatment.

[Obayan]

Re: Fenofibrate (Tricor) and multiple myeloma

by Obayan on Tue Apr 22, 2014 12:52 am

I have had hypothyroidism for 20 years. It has led to high cholesterol that can't be controlled even with medication, and heart disease. I have been on cholesterol medication for many years. I was just diagnosed with multiple myeloma less than a year ago.

[Igor]

Re: Fenofibrate (Tricor) and multiple myeloma

by Igor on Tue Apr 22, 2014 1:40 pm

Thank you for posting this update, Multibilly. Let's hope that it works -- at least I think that it works for you. Do you track your LDH levels? It can be an additional marker of disease metabolic activity. Some spikes in FLC can be related to infections (like colds for example).

I am on the border between MGUS and smoldering, my levels of HDL and LDL are normal, and I am on the lowest possible dose of simvastatin [Zocor]. If your HDL and LDL levels are still not controlled by fenofibrate, may be you need to just increase the dose or add another statin?

[Multibilly]

Re: Fenofibrate (Tricor) and multiple myeloma

by Multibilly on Tue Apr 22, 2014 8:36 pm

Igor: Let me be clear that I don't think you can say that fenofibrate is working for me based on these results and my history....yet.

I only had my LDH measured once about 18 months ago when I went to a major transplant center when I was checking out various specialists (they ran just about every possible test, including my C-Reactive protein level, LDH, etc....as if I was going through a screening for an SCT). My LDH was normal at that time.

I'll keep this suggestion in my hip pocket, depending on where my numbers go next. Thanks.

[Multibilly]

Re: Fenofibrate (Tricor) and multiple myeloma

by Multibilly on Fri Jul 11, 2014 1:43 pm

I got my latest lab results today as I continue my fenofibrate experiment. I'm including my key graphs in this post. My doc and I can’t really say that we are seeing an impact from it by looking at my latest data. My key markers seem to all be within the normal standard deviation (normal fluctuation range) before I started the fenofibrate.

I did add 10 mg of Lipitor back into my regiment and my cholesterol numbers pretty much got back to where they were before I switched from 40mg Lipitor to 160mg of fenofibrate. With this combo of drugs, my HDL actually got above 40 mg/dL for the first time in my life, so that’s encouraging..

So, I will likely just keep on the fenofibrate for another 3 months to see where things go, barring any issues that may come up when I discuss all this with my GP.

As an aside, my hemoglobin (graph also included) has slowly been trending down, which gives us a little concern. But given my other markers are decent, my doc can’t really say that the SMM is causing this just yet. I’m going to try tweaking my diet and supplements to boost my iron, vitamin B12, vitamin B6 and folic acid intake to see if I can reverse the trend that way.

I will also see what my GP has to say about all this. More in ~ 3 months.

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[Igor]

Re: Fenofibrate (Tricor) and multiple myeloma

by Igor on Thu Jul 17, 2014 3:10 pm

Thank you very much for sharing your lab results.

[Twi.28]

Re: Fenofibrate (Tricor) and multiple myeloma

by Twi.28 on Thu Jul 24, 2014 5:23 pm

Hi everyone.

Late to this conversation. For what it's worth, my mom (IgG kappa multiple myeloma) for the four years after diagnosis had all kinds of random elevations/decreases in her entire lipid profile. My mom had never had high cholesterol and had an excellent profile of the lipoproteins. Until multiple myeloma.

Her diet was still the same, but after multiple myeloma, it all changed. In all my researching, I learned multiple myeloma gives some falsely elevated / decreased lipid profile values. For what it's worth, here are some websites I came across. It doesn't seem to be common knowledge amongst GPs or even multiple myeloma specialists? My mom refused statins and their potential multitude of side effects.

A lot of this is pretty technical stuff. I would be curious to know people here think about GPs or internal med docs prescribing statins to multiple myeloma patients who previously had normal lipid profiles and who have not changed diets, eat healthy, have no history of familial hypercholesterolemia, etc..

"Artifactual measurement of low serum HDL-cholesterol due to paraproteinemia", van Gorselen et al, Clin Res Cardiol. Sep 2010; 99(9): 599–602.

"Falsely low LDL-cholesterol concentrations and artifactual undetectable HDL-cholesterol measured by direct methods in a patient with monoclonal paraprotein,"Tsai et al., Clinica Chimica Acta, 09/2005; 358(1-2):192-5

"Multiple Myeloma Patients Have a Specific Serum Metabolomic Profile That Changes after Achieving Complete Remission," Pineda-Lucena et al., Clin Cancer Res September 1, 2013 19; 4770

"Factitious Biochemical Measurements Resulting From Hematologic Conditions," Dalal et al., American Journal of Clinical Pathology, 2009, 131, 195-204.

[Multibilly]

Re: Fenofibrate (Tricor) and multiple myeloma

by Multibilly on Fri Sep 12, 2014 1:35 pm

Thought I would give an update on my fenofibrate experiment.

I got my latest lab results today. In my doc's words, this was the first time that all my markers improved across the board (usually a couple go up and one or two go the other way).

To remind you, I started taking 160mg fenofibrate back in March, 2014 (right after where my IgG peaks at 3320 mg/dL on the graph).

My IgG actually moved out of my standard deviation range this time around, but just barely. For those of you that care about such things, the vertical bars with the end caps on my graphs represent the standard deviation range for this data. To remind you, the doctor doing the fenofibrate clinical trial expected that my IgG would be the marker for which I would first notice improvement, if it should have an effect on my smoldering myeloma.

So, while one still can't draw any conclusions from just one patient sample and this short of a sample period, my hematologist is starting to think that there "might" be something to the fenofibrate ... but that's about as far as he would understandably go with his comment.

The bottom line is that my cholesterol numbers continue to be at my lifetime best with the combo of fenofibrate and Lipitor, I have no side effects from the fenofibrate, and fenofibrate is quite cheap. So, given that my numbers have been slowly improving, I will continue to use fenofibrate and hope that my numbers continue to improve or hold steady.

Again, I want to emphasize that one really can't draw any meaningful conclusions from this data. This could all just be due to a normal trend that I might have seen without taking the fenofibrate and my supplements. After all, markers do tend to bounce around quite a bit with SMM patients. But, I am happy to get this news going into the weekend

By the way, note that fenofibrate was also used in this study:

NJ Robison et al, "A phase II trial of a multi-agent oral antiangiogenic (metronomic) regimen in children with recurrent or progressive cancer," Pediatric Blood & Cancer, Volume 61, Issue 4, pages 636–642, April 2014 (full text available for no charge)

" ... We subsequently demonstrated that the PPAR-alpha agonist fenofibrate has anti­an­gi­o­genic anti-tumor activity, and that the antiangiogenic effects of PPAR modulation are syner­gis­tic with COX2 inhibition and metronomic cytotoxic therapy in a preclinical model [*]. Given the synergistic activity of fenofibrate without added toxicity in vivo, and in view of the poor prog­nosis and limited options in children with pro­gressive disease, it was proposed that fenofibrate be added to the 4-drug regimen for the successor study."

* D Panigrahy, "PPARα agonist fenofibrate suppresses tumor growth through direct and indirect angiogenesis inhibition," Proceedings of the National Academy of Science of the USA, January 22, 2008, 105(3):985-90 (full ext available for no charge)

Now whether the above information could potentially be applied in any way to multiple myeloma is well beyond my pay grade But I find it interesting that folks are experimenting with this drug with other cancers.

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