Dr. SH advised me to keep off the Internet...it's a very depressing place for this, filled with old research, backward-looking forecasts for life expectancies, etc. He recommended only www.cancer.org, so I started there.
But soon, I couldn't help myself because this website just didn't have enough answers. By both nature and professional training, I am used to diagramming options and bottoming out all possible solutions, pros and cons. So I had to learn more.
I also spoke with a few friends. One of them, RH, mentioned that his father, DH, had received an allogeneic transplant about six years ago and that it was not that big a deal and DH was now cured. This was obviously a very tantalizing concept, so I explored it further.
These transplants began back in the 1980s. The first test group experienced a 47% (FORTY SEVEN!!!!) one-year treatment-related mortality rate. That means basically half the people in the study (and there were a few hundred over a ten year period) died from the treatment. In the 1990s, this number improved to about 33%. Still pretty high. Now, the number might be lower and some centers such as Stanford claim to have managed it down further. I wanted to explore just a little bit more.
Another interesting thing I learned is that the reason Dr. BB is in Arkansas is that Sam Walton (billionare founder of WalMart) died from Multiple Myeloma and he donated a lot of money to the University of Arkansas to build a Myeloma center. They hired Dr. BB away from MD Anderson in Houston, which is one of the leading cancer centers in the country, to head it up.
Another friend told me about an organization called Pinnacle Care. Pinnacle Care is a high-end medical concierge and they do everything from scheduling doctor appointments, ensuring records are being sent from point A to point B, doing research on clinical trials and any questions I might have (they have a staff of 12 properly credentialed researchers), accompanying me on doctor's visits to take notes, pre-registering me for appointments and using their network of doctors to get into see physicians that are very, very difficult to schedule. I scheduled a meeting with one of their representatives and discussed hiring them with Jill. They have several levels of membership, ranging from a few thousand a year to get a super-duper physical and a bunch of advice on how to live more healthily to intensive levels of service for someone in my condition. Such levels of service are extremely expensive, so it wasn't an easy choice...but I didn't want to be on my deathbad wondering if I'd done all I could so I mulled it over.
At this stage, there seemed to be a number of schools of thought:
No transplant -- Dr. JB
One autologous transplant -- Dr. SH (and per him, Mayo and City of Hope)
Multiple autologous transplants -- Dr. BB
Allogeneic transplants -- my friend's dad's doctor (Dr. RC) and possibly Stanford
Lots more to research, and lots of decisions to be made.
Jill and I met with EF, a delightful woman from Pinnacle Care who would be my case manager there. I felt very good about the meeting -- she's a very caring person and an RN, which would come in handy. Still, I wasn't certain yet about Pinnacle Care because of the expense, and the fact that the plan I needed was for a six month installment. I felt that I would need some up-front work to determine what treatment was needed, and then nothing more until such time as treatment was to begin. So I decided to wait and see until after I met with Dr. SF at City of Hope.
Thursday, December 18, 2008
Dr. SH Explains My Diagnosis and Treatment Options
On Friday, November 14th I went with Jill to Dr. SH's office. We sat down and Dr. SH gave us a very thorough briefing on the disease, and on the courses of treatment. [I will be embedding the audio here for those that are interested in listening to the conversation...it's lengthy]
As this disease has no cure, there is no consensus on precisely what kind of treatment to give. The overview I provide below comes primarily from Dr. SH and also from some additional research I did. I'm trying to reveal, again, only what I learned at the time.
First, let's talk about staging. There are two systems of staging. One is called the Durie-Salmon system and this has been around for thirty years or so. Interestingly, Brian Durie is one of the doctors I will be speaking with at some point along the line. At any rate, the other system is (I believe) the International Staging System. Both systems have three stages. As I mentioned in a previous post, there is also a "stage 0" of sorts called indolent or smoldering myeloma. This is a low-risk state where people can remain for years (10 years is not unheard of) before progressing to stage 1.
In Stage 1, there is typically no breakdown of bones (no lesions can be seen on the X-ray), no anemia, moderate levels of elevated protein, and low levels of Beta 2 Microglobulin). Almost all doctors agree that stage 1 patients are not treated.
In Stage 3, lesions are observed on the bones, some patients may be anemic, there is calcium in the urine from the bone breakdown and renal function may be impaired, etc. Nasty stuff. All doctors agree that stage 3 patients need treatment immediately.
In between is Stage 2, which is marked very simply by being neither Stage 1 nor Stage 3. Dr. SH told me I was Stage 1. The only symptoms I exhibit are the protein spike (4g/DL) and the bone marrow involvement.
Dr. SH had sent my marrow for extensive chromosome analysis, which can help determine how aggressive the cancer is -- how fast it is moving from stage to stage. If it's fast moving and aggressive, he might recommend treatment immediately even though I am stage 1.
The goal of Myeloma treatment, since it is not presently considered curable, is to achieve remission and keep someone in remission for as long as possible. Generally speaking, the cancer will always return since medicine does not provide the means, currently, to terminate the root cause (the cancer "stem cell" that started the whole thing). There are a number of drugs that are used to bring the cancer into remission, and they have been growing in number and in the proliferation of combinations.
Myeloma used to be treated with chemotherapy alone (Melphalan is a particular type of chemotherapy). These agents weren't very effective at getting the cancer into remission, but they were all we had. During this period, the life expectancy of Myeloma patients was around seven months from diasgnosis. Yippee.
At some point, a class of steroids (not the kinds that build muscle, unfortunately) began to be used. Among these are prednisone and dexamethasone (the latter being about 4-5X the potency of the first). These suppress the immune system and reduce production of the bad plasma cells. It also weakens them somewhat, allowing the chemo to kill more of them.
In the early 1980s, stem cell transplants began to be used, and that extended life expectancies to about 3 to 5 years. Not great, but better than seven months. But I'll get into transplants more in a little bit.
In 2003 or thereabouts, the FDA approved Thalidomide, of all things, for Myeloma treatment. It is believed that Thalidomine works by restricting the growth of blood vessels that are conduits for Myeloma activity. The combination of Thalidomine and a steroid helped to increase life expectancy by another half-year. Baby steps, I suppose.
Around 2005, a very exciting (for those of us with Myeloma, anyhow) new drug called bortezomib (better known by the name Velcade) was approved for use in Myeloma. Velcade is a type of drug known as a protease inhibitor. Essentially, all cells have a mechanism through which they know when it is time to die. This mechanism doesn't work in cancer cells -- they stay alive forever and form tumors. Velcade essentially works to screw up the mechanism that tells them to stay alive. It's been very effective in getting patients into either complete remission (more on this in a moment) or very good partial remission. And it's been even more effective when used in combination with Thalidomide and/or a steroid.
Lastly, a cousin drug of Thalidomide, called Lenalidomid or known by its marketed name Revlimid, has been used.
Different doctors believe in using different combinations of these drugs. Dr. SH suggested he would start me, once treatment became necessary, on Velcade, Thalidomide and Dexamethasone. The latter two are taken orally on a daily basis, and the Velcade is administered in the Doctor's office through injection once a week. Dr. SH noted that his preference would be Thalidomide since Revlimid had not been demonstrated to be superior, and he noted that the MAYO Clinic uses this same protocol, as does City of Hope, which is a prestigious cancer center east of Los Angeles.
Drug resistance is also an issue. If these drugs are used to get the cancer into remission, when the cancer comes back, it may be resistant to some or all of the drugs, depending on how long it takes the cancer to return. If the cancer comes back in six months, it could be a very resistant strain. So we need to balance the need to be effective with the fact that we have only so many drugs in the arsenal, and want to make sure that we have big guns to throw at this thing later on.
These combinations have between 70%-90% effectiveness at getting very good response, or complete remission. Remission, definitionally, is the inability of the doctor to find any disease. Gone from the blood, bone marrow, the whole shebang. Very good partial remission or very good response are terms which refer to what you might guess: a state not which doesn't have complete remission but in which the disease is minimized.
Once I have responded to the treatment, and in the words of Dr. SH at the time "there is no reason to believe you won't" (note: this has subsequently been more or less borne in out some chromosomal analysis, which I'll get into later) the next step in Dr. SH's recommended treatment plan is a stem cell transplant.
Blood stem cells normally reside in the bone marrow and they instruct the marrow to product white blood cells, red blood cells and plasma cells (in normal amounts). The cancerous plasma cells in my marrow now are screwing this up. The disease will get rid of most of them, but some will not be effected by treatment and were I to go off the medicines, the cancer would almost certainly return and would probably do so quickly. Some doctors advocate staying on the drugs only. But most doctors advocate stem cell transplantation as a means of prolonging remission, or at least getting off the drugs (which have some bad side effects, particularly dexamethasone, which at this point Dr. SH downplayed but which I've subsequently learned is a nasty drug).
So...stem cell transplants. There are two kinds: autologous, which uses my own stem cells, and allogeneic (allo-gen-AY-ic), which uses stem cells from a donor. We'll talk about autologous first.
In an autologous transplant, I'll take the drugs mentioned above to bring my cancer into remission or get as close to it as possible. This process will take 4-6 months (several "cycles" of treatment that are essentially three weeks on and one week off to give my body a break from the dexamethasone). Once I have achieved the best response I can (hopefully complete remission), I will then be given a series of injections to "mobilize" the stem cells. That means moving them out of the bone marrow and into the bloodstream. These injections, I have subsequently learned, have flu-like aftereffects but nothing too serious.
Then, for somewhere between one and four days, I'll sit in a chair with a needle in each arm while blood is drawn from one side, circulated through a machine that separates the stem cells from the rest of the blood, and put back into the other arm. Much like a dialysis process. It's not supposed to be painful, although it is supposed to be rather dull since it takes four hours and one can't do much except sit there. I'll have to pick out some good movies to watch.
After they've harvested stem cells, I'll be given a few days to rest up from this procedure. Then the fun begins.
I'll go into the hospital, and will have a central IV line surgically placed near my major arteries and secured beneath my collar bone. This will serve for all blood tests and infusions going forward. Then, for two days, I'll be given what is called a "megadose" of chemotherapy. It will be Melphalan, the same chemo drug that they used to use way back when before all the other novel therapies came out, but the dosage will literally be 100 times what they would normally prescribe. This will be the first part of treatment that will have the traditional chemo side-effects, although they are evidently able to control the nausea now. But I will have mucositis (mouth sores and sore throat are the biggest side effects) and diarrhea and while they can do something to help control these, they are pretty much unavoidable. This is also when I will lose all my head, body and facial hair.
The chemo will kill 99.999% of the remaining Myeloma cells (remember, they can't get all of them, which is why this isn't curable yet). But the chemo will also kill my bone marrow and destroy all my white blood cells, red blood cells, and plasma cells. I will have no immune system, which means I'll get fevers and infections and I will have to have a lot of antibiotics being pumped in through the central line. I will have no red blood cells so I will be anemic and will need blood transfusions. This is why the transplant is necessary.
After the two days of chemo, they will give me a day of rest, and then on day four, they will take the stem cells they harvested, and put them back into me through the central IV line. These stem cells will settle in my bone marrow (this process is called engraftment) and after they've settled, my bone marrow will begin to produce the blood cells again. This takes about 2-3 weeks, after which I'll be discharged, assuming there are no complications.
Sounds fun, doesn't it?
The best part is this doesn't cure the cancer. But it will keep it away. Some people, and we'll get into a few of their stories, keep it away 10 years or even longer. Other people have it return in six months. The median is again about 3-4 years. We'll have to see.
The other type of transplant is an allogeneic transplant. This is similar, except that the blood stem cells are harvested from a matching donor. I'll get into how they determine a match in a future post (remember, I'm sticking to the order in which I learned all this). The advantage to an allogeneic transplant is that I would have an entirely new immune system, which would recognize the cancer as something that should be killed off (something which my own deficient immune system doesn't do well) and it would then be killed off. This is called Graft Versus Host Effect, or Graft Versus Host Disease. The Graft (the new stem cells and the bone marrow they engraft to) attacks the Host (the cancer in my bloodstream). This means that it is potentially curative. However, GVHD can cause major problems. It might reject the rest of my body and try to destroy my organs, etc. For this reason, there have been historically very high mortality rates associated with allogeneic transplants. We'll get into that, too, in a future post. But suffice to say, the mortality rates are still high enough where Dr. SH advises against them at this point.
Now, Dr. SH advised that there were many viewpoints on treatment, and biases throughout the country. Dr. JB, a prominent guy in Los Angeles, advises against any stem cell transplants (we'll call these SCTs in the future to save me time typing) because he doesn't believe they extend life, and Dr. SH agrees, but he believes there is value in being off drugs in-between transplants.
On the other end of the spectrum is Dr. BB, a very prominent guy in Arkansas and something of an iconoclast in the field. He believes in two or sometimes even three transplants in a row, followed by very aggressive post-transplant therapy (which I didn't realize at the time but which involves remaining on Velcade and RevDex for a year or more!!).
This of course prompted me to ask: if Dr. JB says transplants don't extend life, and if Dr. SH agrees, why on earth would Dr. BB suggest two or three? The answer: Dr. BB does believe they do...but nobody else can replicate his data, and there have been accusations of selection bias. There are boisterous arguments, as these things go, at hematological conferences, I am told.
Nonetheless, Dr. SH advised that I see Dr. BB, and someone at the Mayo Clinic, and indicated he would send me for a second opinion to Dr. SF at the City of Hope. I left overwhelmed, honestly, but I felt very good about Dr. SH.
As this disease has no cure, there is no consensus on precisely what kind of treatment to give. The overview I provide below comes primarily from Dr. SH and also from some additional research I did. I'm trying to reveal, again, only what I learned at the time.
First, let's talk about staging. There are two systems of staging. One is called the Durie-Salmon system and this has been around for thirty years or so. Interestingly, Brian Durie is one of the doctors I will be speaking with at some point along the line. At any rate, the other system is (I believe) the International Staging System. Both systems have three stages. As I mentioned in a previous post, there is also a "stage 0" of sorts called indolent or smoldering myeloma. This is a low-risk state where people can remain for years (10 years is not unheard of) before progressing to stage 1.
In Stage 1, there is typically no breakdown of bones (no lesions can be seen on the X-ray), no anemia, moderate levels of elevated protein, and low levels of Beta 2 Microglobulin). Almost all doctors agree that stage 1 patients are not treated.
In Stage 3, lesions are observed on the bones, some patients may be anemic, there is calcium in the urine from the bone breakdown and renal function may be impaired, etc. Nasty stuff. All doctors agree that stage 3 patients need treatment immediately.
In between is Stage 2, which is marked very simply by being neither Stage 1 nor Stage 3. Dr. SH told me I was Stage 1. The only symptoms I exhibit are the protein spike (4g/DL) and the bone marrow involvement.
Dr. SH had sent my marrow for extensive chromosome analysis, which can help determine how aggressive the cancer is -- how fast it is moving from stage to stage. If it's fast moving and aggressive, he might recommend treatment immediately even though I am stage 1.
The goal of Myeloma treatment, since it is not presently considered curable, is to achieve remission and keep someone in remission for as long as possible. Generally speaking, the cancer will always return since medicine does not provide the means, currently, to terminate the root cause (the cancer "stem cell" that started the whole thing). There are a number of drugs that are used to bring the cancer into remission, and they have been growing in number and in the proliferation of combinations.
Myeloma used to be treated with chemotherapy alone (Melphalan is a particular type of chemotherapy). These agents weren't very effective at getting the cancer into remission, but they were all we had. During this period, the life expectancy of Myeloma patients was around seven months from diasgnosis. Yippee.
At some point, a class of steroids (not the kinds that build muscle, unfortunately) began to be used. Among these are prednisone and dexamethasone (the latter being about 4-5X the potency of the first). These suppress the immune system and reduce production of the bad plasma cells. It also weakens them somewhat, allowing the chemo to kill more of them.
In the early 1980s, stem cell transplants began to be used, and that extended life expectancies to about 3 to 5 years. Not great, but better than seven months. But I'll get into transplants more in a little bit.
In 2003 or thereabouts, the FDA approved Thalidomide, of all things, for Myeloma treatment. It is believed that Thalidomine works by restricting the growth of blood vessels that are conduits for Myeloma activity. The combination of Thalidomine and a steroid helped to increase life expectancy by another half-year. Baby steps, I suppose.
Around 2005, a very exciting (for those of us with Myeloma, anyhow) new drug called bortezomib (better known by the name Velcade) was approved for use in Myeloma. Velcade is a type of drug known as a protease inhibitor. Essentially, all cells have a mechanism through which they know when it is time to die. This mechanism doesn't work in cancer cells -- they stay alive forever and form tumors. Velcade essentially works to screw up the mechanism that tells them to stay alive. It's been very effective in getting patients into either complete remission (more on this in a moment) or very good partial remission. And it's been even more effective when used in combination with Thalidomide and/or a steroid.
Lastly, a cousin drug of Thalidomide, called Lenalidomid or known by its marketed name Revlimid, has been used.
Different doctors believe in using different combinations of these drugs. Dr. SH suggested he would start me, once treatment became necessary, on Velcade, Thalidomide and Dexamethasone. The latter two are taken orally on a daily basis, and the Velcade is administered in the Doctor's office through injection once a week. Dr. SH noted that his preference would be Thalidomide since Revlimid had not been demonstrated to be superior, and he noted that the MAYO Clinic uses this same protocol, as does City of Hope, which is a prestigious cancer center east of Los Angeles.
Drug resistance is also an issue. If these drugs are used to get the cancer into remission, when the cancer comes back, it may be resistant to some or all of the drugs, depending on how long it takes the cancer to return. If the cancer comes back in six months, it could be a very resistant strain. So we need to balance the need to be effective with the fact that we have only so many drugs in the arsenal, and want to make sure that we have big guns to throw at this thing later on.
These combinations have between 70%-90% effectiveness at getting very good response, or complete remission. Remission, definitionally, is the inability of the doctor to find any disease. Gone from the blood, bone marrow, the whole shebang. Very good partial remission or very good response are terms which refer to what you might guess: a state not which doesn't have complete remission but in which the disease is minimized.
Once I have responded to the treatment, and in the words of Dr. SH at the time "there is no reason to believe you won't" (note: this has subsequently been more or less borne in out some chromosomal analysis, which I'll get into later) the next step in Dr. SH's recommended treatment plan is a stem cell transplant.
Blood stem cells normally reside in the bone marrow and they instruct the marrow to product white blood cells, red blood cells and plasma cells (in normal amounts). The cancerous plasma cells in my marrow now are screwing this up. The disease will get rid of most of them, but some will not be effected by treatment and were I to go off the medicines, the cancer would almost certainly return and would probably do so quickly. Some doctors advocate staying on the drugs only. But most doctors advocate stem cell transplantation as a means of prolonging remission, or at least getting off the drugs (which have some bad side effects, particularly dexamethasone, which at this point Dr. SH downplayed but which I've subsequently learned is a nasty drug).
So...stem cell transplants. There are two kinds: autologous, which uses my own stem cells, and allogeneic (allo-gen-AY-ic), which uses stem cells from a donor. We'll talk about autologous first.
In an autologous transplant, I'll take the drugs mentioned above to bring my cancer into remission or get as close to it as possible. This process will take 4-6 months (several "cycles" of treatment that are essentially three weeks on and one week off to give my body a break from the dexamethasone). Once I have achieved the best response I can (hopefully complete remission), I will then be given a series of injections to "mobilize" the stem cells. That means moving them out of the bone marrow and into the bloodstream. These injections, I have subsequently learned, have flu-like aftereffects but nothing too serious.
Then, for somewhere between one and four days, I'll sit in a chair with a needle in each arm while blood is drawn from one side, circulated through a machine that separates the stem cells from the rest of the blood, and put back into the other arm. Much like a dialysis process. It's not supposed to be painful, although it is supposed to be rather dull since it takes four hours and one can't do much except sit there. I'll have to pick out some good movies to watch.
After they've harvested stem cells, I'll be given a few days to rest up from this procedure. Then the fun begins.
I'll go into the hospital, and will have a central IV line surgically placed near my major arteries and secured beneath my collar bone. This will serve for all blood tests and infusions going forward. Then, for two days, I'll be given what is called a "megadose" of chemotherapy. It will be Melphalan, the same chemo drug that they used to use way back when before all the other novel therapies came out, but the dosage will literally be 100 times what they would normally prescribe. This will be the first part of treatment that will have the traditional chemo side-effects, although they are evidently able to control the nausea now. But I will have mucositis (mouth sores and sore throat are the biggest side effects) and diarrhea and while they can do something to help control these, they are pretty much unavoidable. This is also when I will lose all my head, body and facial hair.
The chemo will kill 99.999% of the remaining Myeloma cells (remember, they can't get all of them, which is why this isn't curable yet). But the chemo will also kill my bone marrow and destroy all my white blood cells, red blood cells, and plasma cells. I will have no immune system, which means I'll get fevers and infections and I will have to have a lot of antibiotics being pumped in through the central line. I will have no red blood cells so I will be anemic and will need blood transfusions. This is why the transplant is necessary.
After the two days of chemo, they will give me a day of rest, and then on day four, they will take the stem cells they harvested, and put them back into me through the central IV line. These stem cells will settle in my bone marrow (this process is called engraftment) and after they've settled, my bone marrow will begin to produce the blood cells again. This takes about 2-3 weeks, after which I'll be discharged, assuming there are no complications.
Sounds fun, doesn't it?
The best part is this doesn't cure the cancer. But it will keep it away. Some people, and we'll get into a few of their stories, keep it away 10 years or even longer. Other people have it return in six months. The median is again about 3-4 years. We'll have to see.
The other type of transplant is an allogeneic transplant. This is similar, except that the blood stem cells are harvested from a matching donor. I'll get into how they determine a match in a future post (remember, I'm sticking to the order in which I learned all this). The advantage to an allogeneic transplant is that I would have an entirely new immune system, which would recognize the cancer as something that should be killed off (something which my own deficient immune system doesn't do well) and it would then be killed off. This is called Graft Versus Host Effect, or Graft Versus Host Disease. The Graft (the new stem cells and the bone marrow they engraft to) attacks the Host (the cancer in my bloodstream). This means that it is potentially curative. However, GVHD can cause major problems. It might reject the rest of my body and try to destroy my organs, etc. For this reason, there have been historically very high mortality rates associated with allogeneic transplants. We'll get into that, too, in a future post. But suffice to say, the mortality rates are still high enough where Dr. SH advises against them at this point.
Now, Dr. SH advised that there were many viewpoints on treatment, and biases throughout the country. Dr. JB, a prominent guy in Los Angeles, advises against any stem cell transplants (we'll call these SCTs in the future to save me time typing) because he doesn't believe they extend life, and Dr. SH agrees, but he believes there is value in being off drugs in-between transplants.
On the other end of the spectrum is Dr. BB, a very prominent guy in Arkansas and something of an iconoclast in the field. He believes in two or sometimes even three transplants in a row, followed by very aggressive post-transplant therapy (which I didn't realize at the time but which involves remaining on Velcade and RevDex for a year or more!!).
This of course prompted me to ask: if Dr. JB says transplants don't extend life, and if Dr. SH agrees, why on earth would Dr. BB suggest two or three? The answer: Dr. BB does believe they do...but nobody else can replicate his data, and there have been accusations of selection bias. There are boisterous arguments, as these things go, at hematological conferences, I am told.
Nonetheless, Dr. SH advised that I see Dr. BB, and someone at the Mayo Clinic, and indicated he would send me for a second opinion to Dr. SF at the City of Hope. I left overwhelmed, honestly, but I felt very good about Dr. SH.
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