«New York Forum Part 1 September 20, 2014 Page 1 of 30 Speakers: Virginia Klimek, MD Boglarka Gyurkocza, MD Simon Yeung, PharmD, MBA, Lac Jayshree ...»
Benzene is one that’s famous for causing this type of bone marrow problem. It’s possible, although this is still something we’re studying, it’s possible that people are maybe born with an increased tendency to develop this disease. We also know that people who’ve had chemotherapy or radiation therapy for another cancer are more likely to develop MDS as a result to the exposure and the damage to the bone marrow from that chemotherapy or radiation. So, you’re trying to cure one disease and you end up maybe causing or contributing to another and this type of MDS and leukemia that’s caused by prior chemotherapy for another cancer, we call it therapy related MDS and leukemia and we have a strong interest in studying this here and what we found is that on average, it takes about five years for people from like when they get their first chemotherapy to develop MDS. So, 62 months in this study and 60 months in our study here and the diseases that we see it most commonly in are people who are previously treated for lymphoma, breast cancer and gynecologic malignancies and prostate cancer.
We can describe MDS by using these classification systems and these systems are beautifully described in the books that you receive today. So, I’m not going to really go into detail about this, but you’ve probably heard about the FAB and the WHO classification system. Again, the books that you receive today describe them and go into a lot more detail and I’ll let you take a look at that later because it’s not something we have time to go into today, but even outside of those classification schemes, there are other types of MDS or at least MDS that presents with other sort of profiles that don’t quite fit into those categories. One of them is MDS with myelofibrosis. There may be people in the room who have been told they have something called overlap syndrome which means they have MDS, but they also have some features of another condition called myeloproliferative disorders. The therapy related MDS I referred to and sometimes people develop MDS that looks a lot like something called aplastic anemia which is another type of bone marrow failure syndrome.
The International Prognostic Scoring System is a way for us to look at the bone marrow and the blood counts of people who have MDS and it gives us an idea of how they’re going to do with their disease and the likelihood that they might develop this complication called leukemia. This is also described very nicely in the books that you got today and you can sit down with your doctor and talk with them about what your IPSS score is and what that means to you.
We’re developing even better scoring systems to try to predict how people will do with their disease based on cytogenetics. This is a very busy complicated slide, but just to get across the
point that we’re finding that chromosome changes, genetic changes, are extremely important in this disease. They tell us a lot about how this disease will respond to chemotherapy. It tells us a lot about the likelihood of somebody developing leukemia and so just be on the lookout for increased use for this revised IPSS which will really take into account much more so these chromosomes and genetic changes.
Okay. So, you’ve gone to your doctor, you’ve had these tests and MDS is confirmed. So, what’s next? So again, I’m going to talk generally because everybody is different. So, whether or not… what you need to do after you’re diagnosed with MDS really depends on what’s going on with your disease, what are your blood counts? What does your bone marrow look like? Sometimes there’s no treatment needed. We just need to monitor you and there’s people that I’ve diagnosed with MDS and I haven’t given them any treatment for years. I’m just monitoring them. Other people we make a diagnosis of MDS and I have them in treatment within a week or two depending on, again, their blood and their bone marrow counts at the time.
Whether somebody is receiving therapy or not, once you’re diagnosed with MDS, you’re going to always have to be on a sort of a monitoring plan. The doctor is going to have to monitor you blood counts because even if things seem to be stable, your counts stay the same, they don’t go down lower at least initially they have to be monitored because eventually they will change and so you need to be monitored regularly to pick up on those changes.
Some general things to consider about treatment. Just like any medication that you might take for heart disease, kidney disease, lung problems, anything, you and the doctor have to have a discussion about what is treatment going to do for me and what are the side effects going to be?
Are the side effects going to be worse than the treatment? That’s not what we want. We want there to be more benefit than risk to the treatment. So, the types of things that we think about and we talk about when we’re thinking about starting treatment for this disease is is it possible that maybe I can be cured and if so I would be willing as a patient to accept a lot of side effects if I could be cured. Some people want to feel like well, I’m going to try treatment because I want to know that I tried everything I could do. Of course, everybody wants to feel better because people with this disease especially because of the anemia, you don’t feel well and even if you can’t be cured, well, maybe if I can at least keep the disease where it is without getting worse maybe I can feel better and with better disease control. The flip side, the downside, of course, is side effects. Side effect, side effects, side effects, Travel, the time you have to spend in the hospital going to the doctor’s office. Anybody who’s been down the road knows what I’m talking about especially when I tell my patients they have to come into the City from New Jersey like three times a week. Nobody wants to do that.
I’m going to go through some of these treatment options that we have, but not in a lot of detail, but I want to kind of touch on all of them.
So, supportive care for MDS means that we support you. We try to treat symptoms and the way we provide support in MDS is by giving transfusions to treat anemia. If the white blood cell count is low and you’re running into trouble with infections, we use antibiotics to treat infections and sometimes we use antibiotics to prevent infections as well and in addition, we use injections of medicines I call growth factors. These are medicines that can make the bone marrow just work harder to make white blood cells or red blood cells and some of you may recognize some of these names – GCSF, Epogen alpha or Darbepoetin. Those are these medicines that we use to increase the white count and the red blood cell count. We also have two drugs that are FDA approved for MDS that are called hypomethylating agents. The names for them are 5Azacytidine which you probably know… most of you know as Vidaza and Decitabine which you may know as Dacogen. Those are two hypomethylating agents. That’s the type of drug that these are. Lenalidomide which is called Revlimid is a medicine that’s FDA approved for MDS primarily for treating anemia. Every once in a while when people have the MDS that looks like aplastic anemia, we recommend immunosuppression, but we don’t use that very often. In my practice and maybe there are doctors that you work with we talk a lot about receiving treatment in clinical trials if there’s a clinical trial that’s appropriate for you. The reason for that is because we’re always trying to find new treatments recognizing that we don’t have a lot of treatments for this disease and some of these newer treatments may be a good choice for you and so in clinical trials, we’re studying new drugs, we’re looking at drugs like Vidaza and Decitabine in combination with other drugs. So, there’s a lot of different types of clinical trials that are out there. Sometimes when the MDS gets worse and it develops into more of a leukemia-like picture, we actually will go on and use leukemia therapy for this disease. The MDS is still there, but now you also have leukemia on top of that. So, sometimes people actually need to receive leukemia therapy. Last but not least is something called allogeneic stem cell transplant also known as bone marrow transplant or just stem cell transplant. Stem cell transplant is not for everybody because it is very risky and a lot of people just are not strong enough to receive that type of intense treatment. It is one treatment out of all of these treatments that if you can undergo this procedure safely and with some luck, it has the potential to cure people with this disease, but the bottom line is that most people with MDS either don’t have a stem cell donor or they have other medical problems or because of their age, they’re just not going to be strong enough to do that type of intense treatment. However, we’re going to have a speaker following me that will go into different types of transplants and I think she may tell us a little bit about how we’re trying to change that situation that I just described so that we can now maybe transplant more people than we used to be able to.
So just to go back and cover a couple important principles about treatment. Supportive care is the transfusions, the antibiotics and some of those injections, those growth factors I talked about.
Those are the cornerstone of treatment for MDS whether you’re on chemotherapy, having a transplant, no matter what other treatment you’re receiving, supportive care, monitoring, transfusions, antibiotics, that’s a… you’re always going to be receiving those or being monitored to see if you need to receive those. A common question I have is once somebody has to start
chemotherapy, they say, “Well, will I still get supportive care?” Of course. So, that’s going to always be there and sometimes that may be the only treatment that people need.
These are the growth factors I talked a little bit about. The (inaudible 30:00) the white blood cell count and the red blood cell counts and then this is a summary slide I put together just sort of give you an idea of how we choose treatments for a particular person and this is really how we think about it. So if somebody has a low neutrophil count or a low white blood cell count, you can see this column on the left? If somebody has neutropenia or low white blood cell count, the treatment for that person could include antibiotics, some of those growth factors I talked about, those drugs that I mentioned, those hypomethylating drugs, the Vidaza, the Decitabine and then also consideration can be given to going into a clinical trial if there’s one that’s appropriate. For anemia, transfusions are always an option. The Epoietin and the Darbepoetin, those are those injections I mentioned that can help make the bone marrow work harder. The Lenalidomide or Revlimid is another drug that can be used for anemia as I mentioned a few moments ago. Again, these hypomethylating agents can be used as well as clinical trials. For thrombocytopenia that means low platelet count. Remember those are the cells that you need that you to make blood clots and to prevent bleeding. We’re kind of limited with how we can treat that and this problem and so the mainstay for this is transfusions and if somebody is starting to need transfusions, we don’t like to have to continue transfusions. After people start receiving platelet transfusions, we start thinking about starting them on chemotherapy, these hypomethylating agents, because over time you can be resistant to transfusions for platelets. So, we have a shorter list of treatments to treat low platelet count and then stem cell transplant which is the bone marrow transplant can be used in some cases and I know this sounds like kind of a complicated situation, a complicated algorithm to go through and it really is. Again, everybody’s different, but I just wanted to just give you an idea of how we use some of the information from your bone marrow and your blood counts to decide on a treatment for somebody. So if somebody has anemia and they have this chromosome 5 abnormality, I may be more likely to suggest that they go on Lenalidomide. If they have something called a low EPO level, I may be more likely to give them injections to stimulate their bone marrow to make more red blood cells. If somebody has a bone marrow that looks a little bit more like aplastic anemia, this hypocellular marrow, I may be more likely to prescribe therapy that’s usually given for aplastic anemia and if somebody has a lot of chromosome abnormalities, those genetic abnormalities I was talking about, that’s somebody that even if they don’t need treatment right away, I’m going to be watching them more closely because we worry that those genetic changes are going to make the disease change more quickly.
So, another general principle for deciding on treatment for somebody who has MDS comes down to this question of transplant. So when somebody comes in the door to see me or an MDS doctor, one of the first things we have to think about is is that person… do we think that person might be a transplant candidate and if so how soon do we think we need to do that treatment because that changes how we sequence the treatments. It changes how aggressively we pursue testing to see if somebody has a donor, for example. So if somebody comes in the door and I think that they’re healthy and they’re young enough and that they need a transplant, we start that whole workup MDSF2014-NYC-1 New York Forum Part 1 September 20, 2014 Page 9 of 30 very early and I’ll let my colleague talk about that some more, but if I don’t think that somebody is going to be a transplant candidate or if somebody has walked in the door and they said, “I’ve read about this. I’ve learned about this. It’s not for me. It’s not something I want to pursue,” then we focus on nontransplant treatments like the supportive care, the injections I talked about, the chemotherapy when it’s needed and, again, I’ll just emphasize another general principle that for MDS therapy it is not one size fits all. Everybody is a little bit different and those differences including what treatment is used and the timing for that treatment when you start the treatment.