We know that the immune system is not functioning properly in multiple myeloma.
We do stem cell transplants for that reason to attempt to give the immune system a fresh boost having killed off many of the abormal cells.
What I am having difficulty with is why do we use immunosuppressive agents that suppress the immune system further?
Isn't that like killing off your own troops? Particularly, since we know that disease progression is independent of the percent of abnormal plasma cells. So, if an individual has high numbers of functioning plasma cells why are we immunosuppressing them?
Is the rationale that we want to bring in big guns (drugs) and not have troops in the trenches?
It just seems it would be better to have big guns and troops in the trenches.
All of which leads to the question why do we see additive impact of a protesome inhibitor with an immunosuppressant like dex?
Just wondering.
I know some of you multiple myeloma patients may have figured this out already. Please feel free to give your feedback. I welcome the discussion.
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Re: Why use immunosuppressive therapy to treat myeloma?
Suzierose,
An Auto Transplant is just a High Dose of Chemotherapy, usually Melphalan at 200 mg/mg2, and then the patients own Stem Cells are given back. The same malfunctioning immune system regrows, but with less Myeloma cells. The only reason the Stem Cells are taken out and given back to the patient is that it would take the patient much longer to recover if this was not done. The reason it is done is to get as much Chemo as possible into the patient to kill a lot of Myeloma Cells - a 50% reduction in multiple myeloma cells is usually consider a good outcome. Liquefied mustard gas (Melphalan) does not "refresh" a patients immune system and it will not help the troops identify the bad guy (the Myeloma). It is just an effective/efficient way to kill a lot of Myeloma cells.
The reason Doctors will use Dex with Revlimid and/or Velcade in Maintenace after an Auto is because your Immune System still will not identify the Myeloma as a threat/ foreign. I do not think most Doctors discuss this with their patients because current multiple myeloma therapy cannot address this problem unless an Allo transplant is done. thalidomide/Revlimid may temporarily aid in helping the Immune system in destroying the Myeloma, but sadly the Myeloma usually can overcome them and the patient relapses.
After doing an Allo the Immune system may aid the patient in the battle against the Myeloma. Allo patients take Immunosuppressive drugs after an Allo to prevent GVHD. In my case I was fortunate to come out of the Allo in sCR , so I have been able taper off my drugs in the planned manner. If I still had Myeloma Cells, the first thing that would have been done is to take away the Immunosuppressive drugs - not give me Chemo. That is because we are hoping that the Donor Immune systems will function properly and destroy the multiple myeloma cells. If that did not work, we would than likely try Revlimid since that is an immunomodulating agent without Dex, since the Dex would suppress the Donor Immune system.
I hope that helps explain it.
Mark
An Auto Transplant is just a High Dose of Chemotherapy, usually Melphalan at 200 mg/mg2, and then the patients own Stem Cells are given back. The same malfunctioning immune system regrows, but with less Myeloma cells. The only reason the Stem Cells are taken out and given back to the patient is that it would take the patient much longer to recover if this was not done. The reason it is done is to get as much Chemo as possible into the patient to kill a lot of Myeloma Cells - a 50% reduction in multiple myeloma cells is usually consider a good outcome. Liquefied mustard gas (Melphalan) does not "refresh" a patients immune system and it will not help the troops identify the bad guy (the Myeloma). It is just an effective/efficient way to kill a lot of Myeloma cells.
The reason Doctors will use Dex with Revlimid and/or Velcade in Maintenace after an Auto is because your Immune System still will not identify the Myeloma as a threat/ foreign. I do not think most Doctors discuss this with their patients because current multiple myeloma therapy cannot address this problem unless an Allo transplant is done. thalidomide/Revlimid may temporarily aid in helping the Immune system in destroying the Myeloma, but sadly the Myeloma usually can overcome them and the patient relapses.
After doing an Allo the Immune system may aid the patient in the battle against the Myeloma. Allo patients take Immunosuppressive drugs after an Allo to prevent GVHD. In my case I was fortunate to come out of the Allo in sCR , so I have been able taper off my drugs in the planned manner. If I still had Myeloma Cells, the first thing that would have been done is to take away the Immunosuppressive drugs - not give me Chemo. That is because we are hoping that the Donor Immune systems will function properly and destroy the multiple myeloma cells. If that did not work, we would than likely try Revlimid since that is an immunomodulating agent without Dex, since the Dex would suppress the Donor Immune system.
I hope that helps explain it.
Mark
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Mark
Re: Why use immunosuppressive therapy to treat myeloma?
HI Mark!
I understand the reasons for HSCT. I do not understand why we immunosuppress a cancer patient whether they recieve a HSCT or not.
I see why allo is better than auto in terms of a different source of stem cells to replace the dysfunctional abnormal immune system.
Having said that, I do not understand why if over 80% of the plasma cells are normal they are being immunosuppressed.
The immunosuppressive does not kill the 20% abnormal cells but it does prevent the 80% normal plasma cells from fighting against the cancer.
Why is that done?
I also am unclear as to why there is an additive effect of dexamethasone and a protesome inhibitor .
I understand the reasons for HSCT. I do not understand why we immunosuppress a cancer patient whether they recieve a HSCT or not.
I see why allo is better than auto in terms of a different source of stem cells to replace the dysfunctional abnormal immune system.
Having said that, I do not understand why if over 80% of the plasma cells are normal they are being immunosuppressed.
The immunosuppressive does not kill the 20% abnormal cells but it does prevent the 80% normal plasma cells from fighting against the cancer.
Why is that done?
I also am unclear as to why there is an additive effect of dexamethasone and a protesome inhibitor .
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suzierose - Name: suzierose
- When were you/they diagnosed?: 2 sept 2011
Re: Why use immunosuppressive therapy to treat myeloma?
Dear Suzierose,
I think Mark has summarized things quite nicely. At the end of the day, we do not suppress the immune system intentionally (except in the case of an allogeneic stem cell transplant when we are attempting to prevent graft vs. host disease). For patients with myeloma, the immune system has not prevented the disease from declaring itself. As such, we treat it with drugs that are directly toxic to the cancerous myeloma cells themselves. That includes dexamethasone. High doses of steroids can induce myeloma cells to die off. Since Velcade (bortezomib) and dexamethasone both have anti-myeloma effects, when you add them together, you often will see a better treatment effect on the myeloma (unless a particular patient has disease resistant to steroids or proteasome inhibitors).
Unfortunately, most of the therapies we use for myeloma have immunosuppressive side effects. However, the benefits that these drugs have in controlling the myeloma outweigh the immunosuppressive side effects in most instances. The exception to this may be the use of high dose dexamethasone with Revlimid (lenalidomide). Revlimid works in part by bolstering the immune system to target the myeloma more effectively (I must stress though that this is just one of the many properties it has). There are data to suggest that higher doses of steroids blunt this effect. Between these data and the fact that high-dose steroids in combination with Revlimid has more side effects, we typically will use lower dose steroids with Revlimid.
The myeloma community has heard your frustration though! There is a strong push in myeloma and other cancers to develop more targeted therapies that will maintain efficacy but reduce the collateral damage to the immune system (and other systems of the body). Additionally, there is considerable interest in developing ways of bolstering/augmenting an immune response as a way of combatting cancer. So, hopefully in the not too distant future we will be able to battle myeloma effectively without sacrificing any troops!
Pete V.
I think Mark has summarized things quite nicely. At the end of the day, we do not suppress the immune system intentionally (except in the case of an allogeneic stem cell transplant when we are attempting to prevent graft vs. host disease). For patients with myeloma, the immune system has not prevented the disease from declaring itself. As such, we treat it with drugs that are directly toxic to the cancerous myeloma cells themselves. That includes dexamethasone. High doses of steroids can induce myeloma cells to die off. Since Velcade (bortezomib) and dexamethasone both have anti-myeloma effects, when you add them together, you often will see a better treatment effect on the myeloma (unless a particular patient has disease resistant to steroids or proteasome inhibitors).
Unfortunately, most of the therapies we use for myeloma have immunosuppressive side effects. However, the benefits that these drugs have in controlling the myeloma outweigh the immunosuppressive side effects in most instances. The exception to this may be the use of high dose dexamethasone with Revlimid (lenalidomide). Revlimid works in part by bolstering the immune system to target the myeloma more effectively (I must stress though that this is just one of the many properties it has). There are data to suggest that higher doses of steroids blunt this effect. Between these data and the fact that high-dose steroids in combination with Revlimid has more side effects, we typically will use lower dose steroids with Revlimid.
The myeloma community has heard your frustration though! There is a strong push in myeloma and other cancers to develop more targeted therapies that will maintain efficacy but reduce the collateral damage to the immune system (and other systems of the body). Additionally, there is considerable interest in developing ways of bolstering/augmenting an immune response as a way of combatting cancer. So, hopefully in the not too distant future we will be able to battle myeloma effectively without sacrificing any troops!
Pete V.
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Dr. Peter Voorhees - Name: Peter Voorhees, M.D.
Beacon Medical Advisor
4 posts
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