Valcyte: does it work because of its antiviral or immunomodulatory properties (or both)?

[Hip]

I'm just trying to show people on this forum that they are so quick to criticize and say there is no evidence when I say a general statement that Valcyte is carcinogenic, but when someone says ME/CFS is carcinogenic in the same general way of course there is no criticism.

I am glad you brought this up, because you often hear people say on this forum that ME/CFS patients have a higher risk of getting cancer. And I have to admit that although I did not myself think that this was likely to be true, I have never actually thought to pull anyone up on their statements, and ask them "what's the evidence for that?"

But I will do next time! And point them to the study you quoted.

 

[heapsreal]

I am glad you brought this up, because you often hear people say on this forum that ME/CFS patients have a higher risk of getting cancer. And I have to admit that although I did not myself think that this was likely to be true, I have never actually thought to pull anyone up on their statements, and ask them "what's the evidence for that?"

But I will do next time! And point them to the study you quoted.

Dr Peterson who noticed high rates of rare cancers in his cfs patients. Possibly because of low nk function which besides killing viral infected cells they also kill cancer cells. I dont know if there are studies on this but physiologically it makes sense with low nk function and other immune dysfunctions could increase the risks of cancer?

Im sure u will find studies showing increased cancer rates from ebv/cmv/hhv6, valcyte has shown in animals to increase cancer rates with long term use, how long is long term i dont know?? most cfs patients go on valcyte from 6-18months in general to help lower their infectious load, which in itself increases cancer risks. Its a pick your poison but i think the risk of using valcyte for 12 months and being monitored by your dr is low.

I just dont agree with bagging out a treatment that could greatly help someone, if one is concerned of the dangers then lay out the risks and the benefits not just say it causes cancer. the majority of people here know the risks and side effects of valcyte and already know its a drug to be cautious of.

 

[leokitten]

Dr Peterson who noticed high rates of rare cancers in his cfs patients. Possibly because of low nk function which besides killing viral infected cells they also kill cancer cells. I dont know if there are studies on this but physiologically it makes sense with low nk function and other immune dysfunctions could increase the risks of cancer?

Im sure u will find studies showing increased cancer rates from ebv/cmv/hhv6, valcyte has shown in animals to increase cancer rates with long term use, how long is long term i dont know?? most cfs patients go on valcyte from 6-18months in general to help lower their infectious load, which in itself increases cancer risks. Its a pick your poison but i think the risk of using valcyte for 12 months and being monitored by your dr is low.

I just dont agree with bagging out a treatment that could greatly help someone, if one is concerned of the dangers then lay out the risks and the benefits not just say it causes cancer. the majority of people here know the risks and side effects of valcyte and already know its a drug to be cautious of.

Who's "bagging out" a treatment? Surely not me, if you think so then you haven't read this thread and it's purpose.

Again, I TAKE VALCYTE, so I am certainly not the one poo pooing the idea of taking it, you have to read all the context of what was said. This entire conversation is about if Valcyte effectiveness in ME/CFS is predominantly because it suppresses/modulates the immune system, then it's a somewhat dirty drug to achieve this because it does so by being generally toxic to white blood cells. A targeted therapy would be much more desirable.

Also Valcyte isn't a cure it isn't just about taking it 12-18 months and then you're done for life. That's the problem, for most of us it's effects only last so long and after a break then you have to go on it again, over and over in cycles for the rest of your life. All I said is that I would prefer not to do this if we could get a targeted therapy in the near future because Valcyte is toxic. I did my first course of Valcyte for over 14 months and then took a break, now I have to start again on another course because it had some benefits but they aren't permanent.

 

[halcyon]

I'm just trying to show people on this forum that they are so quick to criticize and say there is no evidence when I say a general statement that Valcyte is carcinogenic, but when someone says in such a general way that ME/CFS is carcinogenic of course there is no criticism.

People are going to be very defensive of their one and only treatment option, and they don't want others to be scared off from trying the one thing that might make them better. But I think you understand this well.

I didn't mean to make alarmist general statements, I truly thought it was an accepted fact, based on Dr. Peterson's (thanks @heapsreal, I couldn't remember which other doctor had reported increased incidence) and Dr. Richardson's clinical experience. My doctor even mentioned it to me as well. I thought there was more than just that one published study but I was wrong. I will say that the published study leaves a lot to be desired based on the way it was performed. This topic deserves some real serious study.

 

[heapsreal]

People are going to be very defensive of their one and only treatment option, and they don't want others to be scared off from trying the one thing that might make them better. But I think you understand this well.

I didn't mean to make alarmist general statements, I truly thought it was an accepted fact, based on Dr. Peterson's (thanks @heapsreal, I couldn't remember which other doctor had reported increased incidence) and Dr. Richardson's clinical experience. My doctor even mentioned it to me as well. I thought there was more than just that one published study but I was wrong. I will say that the published study leaves a lot to be desired based on the way it was performed. This topic deserves some real serious study.

The problem with any cfs study is what criteria and many who than got some other illness than lost the cfs diagnosis and said to have say leukemia etc

@leokitten I understand valcyte will probably used off and on. Using it like that will surely reduce cancer risks from valcyte?? Rather than long term or as i took it you meaning continuously ?

did you use any other antiviral in between valcyte courses??

 

[leokitten]

@leokitten I understand valcyte will probably used off and on. Using it like that will surely reduce cancer risks from valcyte?? Rather than long term or as i took it you meaning continuously ?

did you use any other antiviral in between valcyte courses??

I would think in terms of cumulative dosage when assessing cancer risk.

I take huge doses of Famvir all the time, during Valcyte courses and during breaks. As I mentioned before Famvir is also a nucleoside analog but has almost zero toxicity and cancer risk because it is almost completely preferential to herpesvirus DNA vs our own DNA.

 

[Hip]

Dr Peterson who noticed high rates of rare cancers in his cfs patients.

I did not know that. It says here that:

Dr. Peterson got Dr. Mikovits, a cancer researcher, interested when he mentioned at a conference in Spain that he had nine patients with Non-Hodgkins Lymphoma (NHL). NHL strikes about 2 out of every 10,000 people in the US (0.02%) but a full 5% of Dr. Peterson’s Nevada cohort had developed it. Even more striking was the type of specific of type of lymphoma he was finding

Mantle Cell Lymphoma is a form of non-Hodgkins Lymphoma (NHL) that is almost vanishingly rare. If my back of the envelope statistics are correct MCL strikes about 1 out of every 100,000 people …but thirty percent of Dr. Peterson’s ME/CFS cancer patients had it.

So this is the same non-Hodgkins lymphoma that is mentioned in the study @leokitten quoted earlier.

However, an increase in the incidence of one rare cancer is not the same thing as finding an overall increase in the rate of cancer in ME/CFS.

The study cited by leokitten said:

CFS was present in 0.5% of cancer cases overall and 0.5% of controls.

Correct me if I am wrong (I am a bit brain fogged today), but I think that implies there was no overall difference in cancer rate between elderly ME/CFS patients and controls.

 

[SOC]

I am glad you brought this up, because you often hear people say on this forum that ME/CFS patients have a higher risk of getting cancer. And I have to admit that although I did not myself think that this was likely to be true, I have never actually thought to pull anyone up on their statements, and ask them "what's the evidence for that?"

But I will do next time! And point them to the study you quoted.

My specialist has mentioned that the type of immune dysfunctions seen in ME/CFS leave people with those dysfunctions (for whatever reason) more prone to cancer. I don't understand the ins and outs, but my best understanding is that our cancer surveillance systems are impaired, so our bodies are less likely than those of a person without those immune dysfunctions to stop a mutation from progressing.

No, that's not a specific research study on cancer in ME/CFS patients, but it might be a reasonable logical argument. If people with low NK cells, or NK cell function, or low CD8+ (for whatever reason) have an increased risk of cancer, then it's logical that ME/CFS patients with those dysfunctions would have that increased risk.

Dr Peterson, who probably has treated ME/CFS patients longer than anyone and therefore has the best long-term picture, has been very clear that his ME/CFS patients have a noticeably higher incidence of NHL than the average population.

Given that no one has bothered to fund decent research on ME/CFS specifically, the best information we have to go with is information on related conditions (the same immune dysfunction) and the clinical knowledge of our highly experienced specialists.

Certainly, if the main benefit of Valcyte is it's function as an immune modulator, then a cleaner immune modulator would be preferred. The problem is we don't know for certain why Valcyte is working so well for some patients. We also don't know what, if any, currently available immune modulator would work as well without the risks associated with Valcyte.

I don't disagree that there is sufficient evidence that Valcyte may be a potential carcinogen in humans at some dosage (I haven't read enough to know if the risk is dosage-specific). Most of the objection I saw on this thread was to the statement that Valcyte used long term WILL cause cancer. I agree that that statement is unfounded. Now that it is changed to "it is somewhat toxic and carcinogenic", I can agree with it and I suspect most of the people who disagreed with the original statement would agree as well.

Bottom line: There is nowhere near enough research on ME/CFS to make very many definitive statements. We don't know which is riskier for us -- the slight theoretical (there is no retrospective study of long-term use of Valcyte at normal doses in humans) increased risk of cancer from Valcyte, or the slight theoretical (there are no definitive studies of increased cancer risk of untreated ME/CFS) risk of cancer from untreated ME/CFS. There's risk either way. We should all get to make our own decisions about what risks we are willing to take.

 

[redaxe]

When I saw Dr Lerner recently for the first time it didn't seem to take him long to realise that I fitted in with the profile of his regular patients. I remember him saying to me reassuringly "don't worry we know what this is".
When I saw him a second time (after he had all his test results) he diagnosis was persistent HHV6 and recommended Valcyte. But his report also said that after the Valcyte that HHV6 can be held in inactivity with Valtrex.
After further questioning from me I remember him saying to me that "this is where the science is at".

But it seems from this thread that not everyone agrees that persistent EBV, HHV6 and CMV infections are behind this disease.
One key thing is to reconcile the Valcyte antiviral theory with the Rituximab approach. If Rituximab is killing viral infected or viral damaged B cells isn't that a logical overlap with Valcyte's antiviral activity?

EBV is used in medical research to infect and immortalize B cells which can be cell cultured for research purposes - I used to work in labs that did this stuff. Obviously this is what these viruses can do in patients as well. Doesn't HV6 and CMV also invade B cells and essentially surivive and replicate in these cells either directly or through monoclonal cell division (mitosis) where 1 viral infected cell gives rise to 2 viral daughter cells?

I find another interesting observation is that Multiple Sclerosis the major risk factor is EBV. If you haven't ever had EBV infection apparently it is impossible to get MS but if you've had a bad case of EBV (i.e. infectious mono or glandular fever) apparently the risk is much greater. So it seems that MS has a similar controversy as CFIDS. - Does EBV infect and immortalize B cells or does it damage them and disappear leaving damaged immune cells which attack the myelin sheath?

 

[IreneF]

When I saw Dr Lerner recently for the first time it didn't seem to take him long to realise that I fitted in with the profile of his regular patients. I remember him saying to me reassuringly "don't worry we know what this is".
When I saw him a second time (after he had all his test results) he diagnosis was persistent HHV6 and recommended Valcyte. But his report also said that after the Valcyte that HHV6 can be held in inactivity with Valtrex.
After further questioning from me I remember him saying to me that "this is where the science is at".

But it seems from this thread that not everyone agrees that persistent EBV, HHV6 and CMV infections are behind this disease.
One key thing is to reconcile the Valcyte antiviral theory with the Rituximab approach. If Rituximab is killing viral infected or viral damaged B cells isn't that a logical overlap with Valcyte's antiviral activity?

EBV is used in medical research to infect and immortalize B cells which can be cell cultured for research purposes - I used to work in labs that did this stuff. Obviously this is what these viruses can do in patients as well. Doesn't HV6 and CMV also invade B cells and essentially surivive and replicate in these cells either directly or through monoclonal cell division (mitosis) where 1 viral infected cell gives rise to 2 viral daughter cells?

I find another interesting observation is that Multiple Sclerosis the major risk factor is EBV. If you haven't ever had EBV infection apparently it is impossible to get MS but if you've had a bad case of EBV (i.e. infectious mono or glandular fever) apparently the risk is much greater. So it seems that MS has a similar controversy as CFIDS. - Does EBV infect and immortalize B cells or does it damage them and disappear leaving damaged immune cells which attack the myelin sheath?

Rituximab kills all B cells.

 

[leokitten]

I don't disagree that there is sufficient evidence that Valcyte may be a potential carcinogen in humans at some dosage (I haven't read enough to know if the risk is dosage-specific). Most of the objection I saw on this thread was to the statement that Valcyte used long term WILL cause cancer. I agree that that statement is unfounded.

@SOC to be fair I never in any post said "Valcyte will give you cancer". I said originally "Valcyte will give you cancer faster than ME/CFS alone would" in response to the statement "ME/CFS is carcinogenic, so pick your poison".

I'm not an English expert but I know my intention and also that when comparing two things like that it changes the sentence. Given the context and earlier posts there is a big difference because it is saying that "if one of the two give you cancer this one would be faster if you have to take it your whole life".

 

[redaxe]

Rituximab kills all B cells.

So how does this work with your long term immunity. If you kill off all your memory B cells over a short period of time won't that leave you exposed to catching every pathogen that you have been exposed to previously in your life. I mean there are 10s-100s of very nasty pathogens that we get routinely vaccinated for or have been exposed to early in life and we develop long lasting immunity against. So what happens if that defence is stripped away?

I would have thought that would have been fatal but apparently not. So we are now learning that adaptive immunity isn't as critical for survival as we once thought?

 

[SOC]

@SOC to be fair I never in any post said "Valcyte will give you cancer". I said originally "Valcyte will give you cancer faster than ME/CFS alone would" in response to the statement "ME/CFS is carcinogenic, so pick your poison".

I'm not an English expert but I know my intention and also that when comparing two things like that it changes the sentence. Given the context and earlier posts there is a big difference because it is saying that "if one of the two give you cancer this one would be faster if you have to take it your whole life".

That's not the way I remember reading it, but I only got to read it once before you changed it, so I guess I'll have to take your word for it. In any case, there is no definitive evidence which WILL give you cancer faster. That's sheer speculation, which is, I hope, what most of those disagreeing with you were saying. No one is saying it's absolutely untrue, just that it's not absolutely true.

I'm not at all convinced that anyone is disagreeing in content to any great extent in this thread. We're just caught up in some language issues. Perhaps we can continue an interesting and productive conversation if we all agree to avoid unsubstantiated definitive statements. Valcyte might give you cancer faster than ME/CFS alone would. ME/CFS appears to increase risk of some cancers. We have very, very little definitive evidence of much of anything in ME/CFS, so our conversations will likely proceed more smoothly if we keep that in mind and construct our statements accordingly.

 

[IreneF]

So how does this work with your long term immunity. If you kill off all your memory B cells over a short period of time won't that leave you exposed to catching every pathogen that you have been exposed to previously in your life. I mean there are 10s-100s of very nasty pathogens that we get routinely vaccinated for or have been exposed to early in life and we develop long lasting immunity against. So what happens if that defence is stripped away?

I would have thought that would have been fatal but apparently not. So we are now learning that adaptive immunity isn't as critical for survival as we once thought?

You are more susceptible to certain infections after receiving rituximab, mostly respiratory. I was told to practice good hygeine and avoid young children. I was housebound anyway, so it wasn't a problem. I took antibiotics when I saw the dentist. I wore a mask and sat by myself when I got a blood draw at Stanford.

The ritux kills only one stage in the life cycle of the B lymphocyte. The stem cells are in your bone marrow, and constantly regenerate more lymphocytes. (Apparently the life cycle of B cells is quite variable, some people regenerating them faster than others.) It is only one part of a complex system, so you are not completely stripped of the ability to fight off infection.

Because the rituximab doesn't kill off the stem cells and immature phases of B cells, you still still have immunity to diseases such as chicken pox, which you have been exposed to either by getting the infection or through a vaccine.

 

[redaxe]

Thankyou that explains things quite well - did the Rituximab help you permanently?

 

[heapsreal]

So how does this work with your long term immunity. If you kill off all your memory B cells over a short period of time won't that leave you exposed to catching every pathogen that you have been exposed to previously in your life. I mean there are 10s-100s of very nasty pathogens that we get routinely vaccinated for or have been exposed to early in life and we develop long lasting immunity against. So what happens if that defence is stripped away?

I would have thought that would have been fatal but apparently not. So we are now learning that adaptive immunity isn't as critical for survival as we once thought?

I think its a big concern when one has low nk function and cd8 function and has issues with infectious reactivation.

Further reports cant be too far away. Interesting to know their selection criteria?

 

[IreneF]

Thankyou that explains things quite well - did the Rituximab help you permanently?

No.

 

[IreneF]

I think its a big concern when on has low nk function and cd8 function and has issues with infectious reactivation.

Further reports cant be too far away. Interesting to know their selection criteria?

I have low NKC function and variable herpes titers. Don't know about CD8.

 

[OnlyInDreams]

Also Valcyte isn't a cure it isn't just about taking it 12-18 months and then you're done for life. That's the problem, for most of us it's effects only last so long and after a break then you have to go on it again, over and over in cycles for the rest of your life. All I said is that I would prefer not to do this if we could get a targeted therapy in the near future because Valcyte is toxic. I did my first course of Valcyte for over 14 months and then took a break, now I have to start again on another course because it had some benefits but they aren't permanent.

My issue with this comment is the part where you said Valcyte will have to be taken in cycles "for the rest of your life". There is a worthy alternative to Valcyte, it just isn't available yet. Brincidofovir has been given "Fast track" designation and is currently enrolling folks for the Phase 3 SUPPRESS trial. Assuming everything goes as planned with the trials, I read that Brincy will become commercially available in either Q4 2016 or Q1 2017. This drug has the expectation of being 65x more potent than Valcyte AND completely non-toxic, no cancer risk what-so-ever. It will effectively replace Valcyte as a treatment method for CMV and HHV6 (as wells and dozens of other viral infections). So your near future targeted therapy has been identified and is being vetted as we speak.

My plan is to stay on Valcyte until Brincy is released. I think that the cancer risk of taking Valcyte until late 2016 / early 2017 is low. And then I will stay on Brincy for the rest of my life, no breaks.

If you haven't heard of Brincidofovir, you can visit the drug maker's website:

www.chimerix.com

 

[Hip]

This drug has the expectation of being 65x more potent than Valcyte AND completely non-toxic, no cancer risk what-so-ever. It will effectively replace Valcyte as a treatment method for CMV and HHV6 (as wells and dozens of other viral infections).

Good to know that brincidofovir is being fast tracked.

Brincidofovir (CMX001) may be a great drug when it arrives. Brincidofovir is the prodrug of cidofovir (Vistide), which Dr Peterson uses for some of his ME/CFS patients.

Brincidofovir seems to have number of advantages over cidofovir:

Chimerix’s key innovation was attaching cidofovir to pieces of lipids, a type of fat. The lipids enable the drug to be absorbed by the gut, and they also may boost uptake of the antiviral drug into cells infected by viruses. As a result, brincidofovir can be given as an oral pill or liquid suspension, while cidofovir must be intravenously administered. Equally important, the addition of the lipids enables brincidofovir to avoid cidofovir’s toxic effects on the kidneys.

Source: here.

I wonder how much brincidofovir will cost though. Will it be priced beyond the reach of many ME/CFS patients?

Also, will brincidofovir work as well as Valcyte for treating ME/CFS?

If Valcyte's anti-inflammatory effects (it's a potent microglial inhibitor) and its immunomodulatory effects are part of why Valcyte helps ME/CFS, and if brincidofovir does not possess these mechanism of action, then brincidofovir may not replace Valcyte.