MD Anderson Cancer Center
Lisa Garvin: Welcome to Cancer Newsline, a podcast series from the University of Texas, M. D. Anderson Cancer Center. Cancer Newsline helps you stay current with the news on cancer research, diagnosis, treatment, and prevention providing the latest information on reducing your family's cancer risk. I'm your host, Lisa Garvin. Today, our guest is Dr. Sheeba Thomas. She is an Assistant Professor of Lymphoma and Myeloma here at M. D. Anderson and our subject today is multiple myeloma. Dr. Thomas, multiple myeloma is somewhat like leukemia in that it's a cancer of the blood? It's not a solid tumor.
Dr. Thomas: Correct. It's a cancer of a particular type of white blood cell called a plasma cell. There is a white blood cell called a lymphocyte that is normally used to fight viruses and when it is in its most mature state, we call it a plasma cell. Plasma cells in normal circumstances are useful as memory cells, they remember infections you've been exposed to before so that when those come back again you already have a mechanism by which to remember them and fight them off more easily than you did the first time.
Lisa Garvin: So with multiple myeloma, I guess, the cells are released, and cells of course blood cells are produced in the bone marrow, and then they move to the blood stream as they mature, but I guess in... what happens with myeloma patients?
Dr. Thomas: Normally, we don't see myeloma cells in the blood stream unless the disease has become quite aggressive, but certainly because this is a cancer of a type of white blood cell, certainly this manifests as sort of a system wide process usually. In some cases, we see what's called solitary plasmacytomas, which is a, a single collection of, you could say, multiple myeloma cells, abnormal plasma cells that are isolated to one part of the body in which case we treat the disease differently than when this is a system wide process, which we call multiple myeloma.
Lisa Garvin: Let's talk about the risk factors for multiple myeloma. It seems to be a disease of older mainly African-American men.
Dr. Thomas: Yes, the median age of diagnosis is roughly 67 years. As you mentioned, it affects more men than women, more African-Americans than Caucasians, approximately 21,000 cases will be diagnosed in the United States this year 2012, about 10,000 people will unfortunately die of this disease this year.
Lisa Garvin: And you said multiple myeloma kind of covers a spectrum from maybe less aggressive to more aggressive. Kindly talk us through the spectrum of multiple myeloma.
Dr. Thomas: Sure, one end of that spectrum are people who have, what we call, a precancerous condition called a Monoclonal Gammopathy of Undetermined Significance. So these are people who have some of these abnormal plasma cells in their system, those abnormal cells produce an abnormal protein that we call an, a paraprotein or an M-protein or an M-spike, those are all terms you might hear, but that, it stays at quite a low level. 1% of people who have this MGUS, this monoclonal gammopathy each year will go, may go on to develop multiple myeloma or other blood cell disorders, others will live with this, but die of something unrelated to this. The other end of that spectrum are people who we say have symptomatic multiple myeloma. These are people who have this abnormal blood cell, this abnormal plasma cell that produces an abnormal protein and it is being produced in sufficient quantities that its actually causing them problems, be it bone lesions, where they are or lytic lesions we say of bone, which are sort of holes in the bones that are at risk for fracture. They may have anemia. They may have high calcium levels in their blood, which may make them feel fatigued. It can cause abdominal pain, constipation, confusion, nausea. We can see problems related to kidney failure and frequent infections. And then there's sort of a middle ground, people who we say have asymptomatic multiple myeloma, so these are people who indeed have multiple myeloma, meet the criteria for multiple myeloma, but they don't have what we call end organ damage. They're not having significant problems because of the anemia.
Lisa Garvin: Obviously, you have to classify these correctly at diagnosis for the best treatment outcomes.
Dr. Thomas: Absolutely, so these... the current standard of care is to follow patients who are in the asymptomatic phase of myeloma as well as in, as well as who have MGUS, this precancerous condition, on a program of observation. Certainly, we follow people who have asymptomatic multiple myeloma on a more close program of observation than those who have MGUS, the precancerous condition, but in both cases, they, these are not, we have not found that treating people before they develop symptomatic myeloma impacts the, what we call, the natural history of the disease. It doesn't affect how long people live with multiple myeloma.
Lisa Garvin: Now the symptoms that you gave, and this is typical of a lot of cancer symptoms, things like nausea, fatigue, these just could be chalked up to, you know, being tired or whatever, how do multiple myeloma cases tend to present or be diagnosed by doctors?
Dr. Thomas: The people who present with asymptomatic disease are often diagnosed because they go to their doctor for their routine physical and they might, they're found to be slightly anemic or they have an elevated protein level in their blood on routine blood work. Those who present with symptomatic myeloma they're often diagnosed because they have bone pain or more profound anemia that leads to fatigue, and then some people present because of frequent infections.
Lisa Garvin: How often, well, I guess, you can't really stage myeloma, you just have kind of the spectrum, I mean in typical cancers you have stage one, stage two, stage three... Do you do that with myeloma?
Dr. Thomas: We do. The most commonly used staging system at this time is called the International Staging System for Multiple Myeloma. This is based on two blood tests - one is called the serum beta-2 microglobulin, the other is called the serum albumin. And based on the levels of these factors, we stage, the, there is a three, three-tiered staging system, so stage one, two, and three.
Lisa Garvin: And when, when treatment becomes necessary, typically, it's high dose chemotherapy with a stem cell transplant to follow?
Dr. Thomas: There are phases to therapy. So for any patient who requires therapy for their multiple myeloma, they would start with what we call the induction phase of therapy. The purpose of the induction phase is to control symptoms quickly, to reverse end organ damage, meaning to reverse kidney failure or high calcium levels, to improve blood counts. The goal is to use that induction phase to control the disease rapidly and in patients who are candidates for autologous stem cell transplant meaning that they're up and about, that they, they're, they don't have a lot of other medical problems that complicate their condition. Those are people who we would follow after induction therapy with a stem cell transplant.
Lisa Garvin: And autologous meaning that you're harvesting their stem cells as opposed to getting them from a donor?
Dr. Thomas: Absolutely, so the standard of care is certainly to use an autologous stem cell transplant. We don't generally do allogeneic stem cell transplants meaning donor transplants upfront and certainly not off unless it's on a clinical trial.
Lisa Garvin: So what happens, so I, and where, is there high dose chemo before the stem cell transplant to kill the cells? Can you kind of explain that process going from the chemo to kill the cells and then reimplanting the new stem cells.
Dr. Thomas: Sure, so the process, so after the induction phase of systemic therapy for multiple myeloma, we are, so we're using the induction phase rather to control the disease and then the stem cell transplant we use as sort of what we say consolidation so to try and drive the level of disease down further. Some people think of it like a, a multiple myeloma like a glacier, there's what you can see above the waterline and then there's the rest of that glacier below the waterline, so if we use induction phase to try and drive, melt that glacier down as close to the waterline as we can, we use the stem cell transplant or that consolidation high dose chemotherapy to drive it hopefully to the waterline or even below the water line so that it takes longer for the disease to come back and cause a problem. The process of the stem cell transplant is to first collect the stem cells, so the to collect the stem cells patients are given an injection called Neupogen or filgrastim that helps to bring the stem cells out of the bone marrow into the blood stream. A catheter and a large IV is then, is inserted into the vein that sits under the collar bone, it's called the subclavian vein and then the blood counts are watched each day in the stem cell transplant center until they get, until the stem cells get to a good number in the, in the blood stream, once that number is hit, that the catheter that has been inserted is hooked to apheresis, a machine called apheresis machine and that machine will filter out and hold aside the stem cells and the rest of the patient's blood is returned to them. Once those stem cells have been held aside and frozen, the patient is then a few days later either admitted to the hospital or this actually, can actually be done as an outpatient. They are given, they can be given high dose chemotherapy, usually with a drug called melphalan and then shortly after that the patient's stem cells are reinfused and the whole purpose of the re, stem cell collection and the reinfusion is that that high dose chemotherapy not only kills the myeloma cells, but it kills the normal blood cells, and so you could the, a patient, a person's body could not withstand the intensity of the chemotherapy unless they, that backup of stem cells is infused back to repopulate the body with normal blood cells.
Lisa Garvin: And do the patients have to go into a protective environment because they're obviously, you know, their immunity is down, do they have to, like with leukemia patients they go into a protected environment for a short time. Is that true?
Dr. Thomas: So with autologous stem cell transplant it's, it's a little bit different, we're actually, they're actually trying to do more of these stem cell transplants outpatient because we figure that the infections that people get outside of the hospital are actually less, can sometimes be less severe or they are less resistant bugs, less resistant bacteria than those that we see in the hospital. So when a patient, a person is relatively healthy and has a good family support system, they are then, the stem cell transplant teams here are trying to do these stem cell transplants outpatient. When people have other complicating factors, maybe their kidneys don't work so well or their heart needs to be watched a little more closely, then they are kept in the hospital.
Lisa Garvin: Dr. Thomas, are there any new exciting treatments or innovations on the horizon for multiple myeloma?
Dr. Thomas: Absolutely. So just by way of background, you know, until... for many years, the from actually, Dr. Alexanian, who is one of our most senior colleagues here, he pioneered the use of melphalan and prednisone, that was in the 1960's and until approximately the 1980's that was the only real therapy for myeloma. Starting in the 1980's, we started using other chemotherapy drugs vincristine, doxorubicin, and dexamethasone in combination and then stem cell transplants came in around that later in the 1980's as well, but really starting in the 1990's that ushered in the era of novel agents. Many people are familiar with the drug thalidomide because it used to be given to pregnant women in the 1950's and unfortunately caused pretty severe birth defects, it was of course taken off the market, but later found to be effective for multiple myeloma and brought back into, brought back on the scene because of its effectiveness in multiple myeloma and some other disorders. There are new, thalidomide on its own, when combined with or thalidomide when combined with dexamethasone produces response rates of about 65 to 72% when given to previously untreated patients, the next generation, we could say, is called lenalidomide. Lenalidomide when combined with dexamethasone provides response rates of 85 to 90% in previously untreated patients. There is now a drug in trials called pomalidomide also in this family and that is now being studied, under study in the relapse setting. We haven't yet tried it in the frontline setting, but that is certainly a drug that people that we are, we are watching and certainly in people who have relapsed it is people are responding to it even if they have failed Revlimid, prior Revlimid and prior thalidomide, so that's an exciting drug. Another drug to watch is the drug called carfilzomib. So around, also in the 1990's, there was a, there was a drug developed called bortezomib or Velcade that's a very effective drug for multiple myeloma. It also, when combined with dexamethasone, provides response rates of about 85 to 90% in previously untreated patients, but one of the side effects of bortezomib is that it can cause neuropathy, numbness and tingling, particularly in the hands and feet. Carfilzomib is related to bortezomib, one of the nice things about carfilzomib is that it doesn't cause neuropathy and particularly in our, in patients with multiple myeloma as people are living longer, quality of life is something that we're thinking more and more about, and so carfilzomib may provide a nice option for patients and that's another drug that we are quite excited about.
Lisa Garvin: In closing, do you have words of encouragement for people who have been diagnosed with multiple myeloma?
Dr. Thomas: Absolutely. Two thoughts come to mind. One is we used to say that the median survival with this disease was 3 to 5 years, but that was in the era before drugs like thalidomide, lenalidomide, bortezomib have come out and now we have yet another generation of these and many other drugs coming, which are extending the options... or improving the options for patients, and therefore, we think translating now into an improvement in overall survival. The other point I would say is that in a recent analysis of patients that was done by Dr. Alexanian actually, he went back and looked at a patient treated in the 1980's and 1990's and saw that there's a small fraction of patients who he might, we might actually say are being cured. It's only about 3% of patients, but this is the disease that we never really talked about cure before, and so, but there are some patients that have who achieved a remission, a complete remission, and now more than 11, 12, 15 years later they're actually maintaining that remission. So we think that they might actually be cured, and so that's another exciting thought.
Lisa Garvin: And that is good news for people with multiple myeloma. Thank you Dr. Thomas for being with us today! If you have questions about anything you've heard today on Cancer Newsline, contact Ask M. D. Anderson at 1877-MDA-6789 or online at www.mdanderson.org/ask. Thank you for listening to this episode of Cancer Newsline. Tune in for the next podcast in our series.
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