Progress and Promises of Leukemia Therapy Webcast December 14, 2010 Olga Frankfurt, M.D. Christy Moore. Introduction

Transcription

1 Progress and Promises of Leukemia Therapy Webcast December 14, 2010 Olga Frankfurt, M.D. Christy Moore Please remember the opinions expressed on Patient Power are not necessarily the views of Northwestern Memorial Hospital, its medical staff or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. That s how you ll get care that s most appropriate for you. Introduction Leukemia is a cancer of the blood, and diagnosis and treatment can be challenging. Fortunately, research is advancing, and progress is helping us treat leukemias better. Coming up you'll hear from a hematologist-oncologist from Northwestern Memorial Hospital and the Lurie Cancer Center as she discusses the latest in leukemia and why patients should be hopeful. It's all next on Patient Power. Hello and welcome to Patient Power sponsored by Northwestern Memorial Hospital. I'm Andrew Schorr. Our topic today is the latest in the diagnosis and treatment of leukemia. It's a very personal topic for me because, happily, I am a 14-year chronic lymphocytic leukemia, or CLL, survivor and doing well. And hopefully I'm a symbol for people of how modern science can make that happen. I'm very grateful. I was in a clinical trial, and we'll discuss that today with a leading expert from Northwestern Memorial Hospital. We're just doing this program soon after the annual meeting of the American Society of Hematology. That's where thousands of doctors and researchers from around the world come together to discuss leukemia and other blood-related conditions. So let's meet our lead expert, and that is Dr. Olga Frankfurt. She is on the staff at Northwestern Memorial. She's a specialist in leukemias and transplant. She's also an assistant professor of medicine at Northwestern's Feinberg School of Medicine. Dr. Frankfurt, I know you attended the American Society of Hematology, or ASH, meeting. When you think about what was discussed related to leukemia, both chronic and acute, is it a positive story these days? Hi, Andrew. Absolutely, the meeting had tremendous amount of information. There is a significant amount of research all over the world aimed at understanding and treatment of leukemia. We have a lot of new information on the molecular characteristics of various leukemias and novel agents, more importantly for patients, novel agents that are active. The difficulty is that it takes a long time from the laboratory to clinical practice, so we'll have to do clinical trials to see which of those promising new agents will become real medicines, but the meeting itself was full of information on leukemia.

2 Wow. And we've seen from the previous meetings that medicines have developed, and we'll talk about some of these leukemias, for mine, chronic lymphocytic leukemia, or CML, chronic myelogenous leukemia, certainly more medicines than ever before. Absolutely. And those are kind of medicines that we'd love for patients to have. They're oral agents. They are very well tolerated. They have very reasonable side effect profiles, but those medications are chronic at the moment meaning that while you are taking them the disease is under control. The goal would be to of course improve on that and be able to cure those disorders. That's the big C word, not cancer but cure, absolutely. That's right. Christy s Story Well, let's hear one person's story first, and you play a role in that, but I want to introduce our audience to Christy Moore who joins us from Rockford, Illinois, northwest of Chicago. Christy is in sales there, and she's really a newlywed. But, what, a couple of months before your wedding your shoulder was bothering you and you went to the emergency room and brought your mother, I guess, and your sister along. Is that right, Christy? You were actually looking at wedding invitations and they joined you at the ER to see what was going on with your shoulder pain? Yes. Hi, Andrew. That's exactly what happened. It was almost three years ago. It was two months before my wedding, and for about a week I had this weird stomach cramping slash shoulder pain, and it would come and go, so I wasn't really sure what was going on. And at one point the shoulder pain just became so unbearable that I thought, you know what, this isn't right. I need to go get this checked out. At the time I was living in downtown Chicago, luckily, close to Northwestern, so I went to the emergency room there and told them that I thought I had torn my shoulder, so Right, because you had been working out to get in shape to be beautiful in your wedding dress, right? Of course. Doesn't everyone do that? 2

3 Right. Right. So they did an x-ray, and it didn't show anything, right? Right. So they did a blood test, which was smart thinking, and tell us about when the doctors came in with the results of the blood test. Yes. So actually two doctors came in, and that's when I thought it was definitely strange, and they looked at me and my mom and my sister and they said, we have information to share, is it okay to share this in present company. And I sat up, and I thought, well, of course. And that's when they said your blood counts came back, and your white blood cells are equivalent to that of a leukemia patient. And when they said that I thought, well, okay, well, what do I have? And that's when they said you have leukemia. And did you know what leukemia was? No. Immediately, the first two thoughts that went through my mind were what is leukemia? And is there a cure for it? Right. And of course when I was diagnosed with leukemia it wasn't clear to me that it was in fact a cancer of the blood. Right. And I had no idea. Well, of course then they start paging the specialists, and the specialist who came out of the rain, who had been on her way home, for you was Dr. Olga Frankfurt, our guest. Yes. And she came in. We're going to hear her side of the story in a second, but she comes in, and of course the question was what was going on, what type of leukemia, how advanced, what was going on. What did she do? What happened? 3

4 Well, right, because the emergency room, they still wanted to do other testing, and she came in, she was the guardian angel that came in from the storm, and immediately she was extremely decisive. She had a very good sense knowing exactly what I was going through just by feeling my spleen, which had been causing the pain because it was so enlarged. It was pressing on my diaphragm that was connected to a nerve that ran up to my shoulder, and she knew exactly what was going on. Wow. And then you were admitted to the hospital. Correct. All right. Dr. Frankfurt. Diagnosis and Evaluation Oh, I remember this, and thank you for the guardian angel thing. That's very sweet. But I remember getting a phone call from the ER, and they told me that they had a woman with acute leukemia, and the story was that she has a shoulder pain and they think it's a blood clot because she has difficulty taking a deep breath. Well, I took a quick look at the blood count and it was pretty obvious. I mean, there's no guarantees in leukemia, but it was pretty obvious that it's not acute myeloid leukemia but it's likely chronic myeloid leukemia and it's probably in a very advanced stage, so it effectively behaved like an acute leukemia, but it has different mechanism of action and therapy would be different. So when I came to see Christy in the ER and examined her, and it's exactly what it was. She had a big spleen and it causes referred pain to the shoulder, so her shoulder was hurting because of her spleen. Right. Let me see if I understand. So someone has like a high, super high white count, and I think normal is, what, 5- to 10,000. Depending on the lab, something like that, yes. Right. And yours was what, Christy, 200 and something? It was 165,000. 4

5 That's right. So your spleen is cleaning the blood and is it that these white cells get sort of stuck there and then it begins to get enlarged? That's probably some of the mechanism how that happens, but in chronic myeloid leukemia the spleen does grow to a very large and uncomfortable, normally the spleen is the size of the fist and it sits under your rib cage so in a normal situation you cannot feel the spleen at all, and in Christy's case I could easily feel it below the rib. So you decided you wanted her admitted to the hospital. Oh, there was no question. Right. Here's the woman, two months before her wedding. She has this chronic myelogenous or myeloid leukemia and then the question is, well, how advanced is it? You had a sense that it was advanced, but what happens to the blood? What other players come together at Northwestern to understand what is an individual patient's situation? That's right. So the clinical suspicion or clinical guess is what I brought into the game, but of course you have to prove and you have to confirm what exactly, what kind of disease it is. And as modern medicine advances that becomes more and more important every year because novel information, novel genetic markers come that determine the response to therapy and overall outcome. So a lot of tests need to be done to determine what exactly, exactly this patient has. So we usually, we evaluate the blood and that gives us a quick assessment, and then we have to perform a bone marrow biopsy because bone marrow is where most of the cells are made and that gives you a very good understanding of what's happening. Some additional molecular study will have to be done. In chronic myeloid leukemia there's specific chromosome abnormality that you look for, and all of those tests had to be done. All right. So the team that helps you with all that, you're a hematologist-oncologist, but for instance I would think pathologists looking under microscopes and other tests they do 5

6 You are absolutely right, Andrew. You are absolutely right. We have a world-class hematology-pathology group. They are expert. They are some of the best in the country, and without them my work would have been impossible. So they help you understand exactly what you're dealing with in Christy's case or anybody, and, as you said, increasingly now you're sort of doing genetic profiling of someone's leukemia because there are different approaches for different subtypes of a disease. Is that correct? You are absolutely correct. Okay. So what we found out with Christy was she was in an advanced stage. I think you call it blast crisis. You're right. It's CML blast crisis. Which is not good, and none of it's good, but of course that is really advanced. So you were in the hospital for a while there, Christy, several days, right? Two weeks. Treatment Approaches Two weeks. Okay. And you started taking one of these newer medicines that you were referring as we talked about the big convention, Dr. Frankfurt. In her case it was a drug that commercially is known as Sprycel. There are three approved medicines we should mention now. Gleevec, Tasigna is a second generation, as is Sprycel. That's correct. And maybe others coming. So the idea was could that knock back the leukemia and manage it chronically at least for a little while. Was that the approach, Dr. Frankfurt? 6

7 That's right. So the standard approach to patients like that before those drugs was just a big chemotherapy, aggressive strong chemotherapy. And in CML blast phase even the big chemotherapy does not work very well, and dasatinib just came about. The reason I knew the drug well was because we've been involved in clinical trials early on using the drugs. I had used it a lot, I felt very comfortable, I knew exactly how it was going to behave. And at the time when we gave Christy Sprycel by itself that was not a standard of care. It is a standard of care now, but back then it wasn't experimental because the drugs had been used in humans and we knew the outcomes, but in this specific setting most people at the time would have recommended using chemotherapy in combination with this drug. But I knew that the wedding was coming and I knew no bride would like to be bald, and I also knew that this drug is very, very active. I mean, obviously if I thought that chemo was absolutely essential to save her life I wouldn't care about her looks at her wedding, but because I knew that this drug would be very active we just started on the single agent, dasatinib, or Sprycel. Right. I want to make a point to our listeners. Whether you're concerned about CML or CLL or any of the different leukemias, there is an art to hematology-oncology, and a lot of it starts with experience at academic medical centers certainly like Northwestern Memorial. That's where trials typically happen. That's where subspecialists like Dr. Frankfurt get experience with these medicines often years before they are approved by the FDA, and they also understand how they can work with other medicines that are either already on the market or others that are in research. And so that's what goes through your mind with an individual's situation, right, Dr. Frankfurt? That's right. What's your experience and as you understand different drugs how can they work and when? Now let's talk about the when. So you had the wedding, Christy, how did you feel? Did it knock back your white count, and did you feel good at your wedding? I was as good as new and actually through almost the whole experience of this I felt amazing. That drug is a miracle without a doubt. I had a wonderful wedding, wonderful honeymoon. I was totally in remission. Right. And for many people, you mentioned, Dr. Frankfurt, that their leukemia is managed chronically, but here's a woman that ideally, if we could, we'd want a cure, correct? 7

8 Absolutely. Because when it presents in such an aggressive form and this extends through today as well, that had not changed yet, the transplant is the only curative regimen available for patients with this advanced phase of chronic myeloid leukemia. Now, it's changing a little bit. Now that maybe in the future we will be able to avoid it, but back then and still right now transplant is the only way to cure this condition. Let's help people understand. We talk about transplant, there are two types. One is where you knock back the cancer and someone gets their own cells back that had been cleaned up. And the other one is to get as best we can a matched donor. Now, in either case you're going to get some chemotherapy. In a younger person their fertility is an issue. Christy was a newlywed with the hope of a family, right, Christy? Yes, of course. Absolutely. For sure. Okay. How many kids are you hoping to have someday? We'll shoot for two, and we'll be very blessed. I'll even take one. And knowing that some of these chemotherapy drugs are harmful to fertility Northwestern has what's called an oncofertility program, and we've done another program on that, another discussion. So that came into play. That's another sort of specialty that came into play as well before you could move forward with the idea of a transplant for Christy, right, Doctor? Well, actually a lot more had to happen prior to either chemotherapy or transplantation. There are multiple tests that need to be done to make sure the patient is fit to undergo that. I mean, in somebody as young as Christy chances are the heart is good and the lungs are good and there's no teeth abscesses anywhere, but all of that has to be checked prior to starting chemotherapy. Right. And is there a match as well, checking the registries. When I met Christy, when I knew what she had, it was not even a question whether she needs to have a stem cell transplant or not, so testing on her, I don't know if they were sent from the emergency room, but definitely within the first few days of her being in the hospital, because I knew that was inevitable and the 8

9 sooner we all identified the donor the better we are going to be. I mean, we tested the sibling first and then we moved very rapidly to try to identify an unrelated donor. And your sister was not a match, Christy? No, she wasn't. All right. So you actually did have eggs harvested, and you have frozen embryos put away right now for when you and your husband are ready to go for it, right? Correct. But then there was a match found, right? I understand a man you don't know but a man somewhere in the US was found to be virtually a perfect match, Christy? Yes. There was actually only one person we found that was a 10 out of 10 match for me. And I don't know the science of it, but having that 10 out of 10 I really think made such a huge difference. And if I could just make a plug for that, and if people can go to marrow.org and register I think that is so important to get that word out, because people don't realize how hard it is. It's much harder than just finding someone that has the same blood type. That's right. Right. And in your case you had a heritage where I believe there was some Native American heritage in there. Correct. Mixed in with probably European heritage as well. Yes. 9

10 So who matched up that way? And it makes a difference. And I know in the African-American population and some others it's harder, so we should all consider being typed so that we can help another. In your case you had the transplant how many months later after the wedding? December 28th, so two months. Two months after the wedding now you're going through a transplant, and you were in the hospital several weeks over Christmas and all that. Did you tell me you were shaving your head over Christmas? Yes, my dad shaved my head on Christmas day because I wanted to be in control of the hair, so we just shaved it. And so it's not easy, a transplant is not easy. One fellow who I once interviewed about a transplant said, look, it's no walk in the park, but it gives you the chance of a cure. How has it worked out, Christy? Oh, my gosh, wonderfully. I am living a happy, healthy life just with much more appreciation for the important things of life of friends and family, so I wouldn't change anything. And it appears that, I'd like to use the C word, cure, but certainly there's no evidence of disease. Is that correct? Yes. Absolutely yes, no evidence of the disease. We are checking molecular studies on a regular basis, and since the transplant there is no evidence of the disease coming back on the most sophisticated levels that we could check. Christy, we're going to hear more from you, but how do you feel about how this worked out? I mean, you were diagnosed with something you had never heard of, and it was super serious, and as you approached what would have been the happiest time of your life, with a wedding. When you look back on this and the care you got starting with going to the ER and Dr. Frankfurt swooping in and the whole team you've heard about, how do you feel about it? 10

11 Well, and we looked at a lot of different places from Seattle to Texas to New York. We flew out and analyzed all of our options, and without a doubt, from the doctors, Dr. Frankfurt to the facility itself, overwhelmingly Northwestern was our choice. And I'm not just saying that because this is for Northwestern, but I absolutely would never, ever change anything about the treatment, the care, from beginning to end. I am so thankful for Northwestern. I actually get choked up even thinking about it. Well, we're going to hear more from you along the way, but, Dr. Frankfurt, I think for you at Northwestern or wherever a leukemia specialist might be, just knowing someone's story with a positive outcome this is what it's about, isn't it? It absolutely is, sir. It is absolutely is. And the majority of our patients, that's their experience. I mean, I want to touch on something Christy's mentioned. In addition to when somebody comes in the emergency room or clinic and the diagnosis of leukemia is given, it is just the most overwhelming, scary, stressful time for the patients and their family, and so many things need to happen, and things need to happen fast. I mean, suddenly the patient needs to understand what leukemia is, become an expert in leukemia, make a choice or at least listen to the choices that are available for the treatment, undergo multiple testings, undergo the fertility evaluation and decide whether they want to consider preserving the possibility of having children in the future. So many things happening at once that it's very crucial to have a really good team. And nursing staff in hematology-oncology, I can never say enough how wonderful they are. I've actually had a family member who was in the oncology floor and I was a patient for a change instead of a physician, and it is unbelievable experience to have nurses like ours -- professional, understanding the disease and caring for patients. They were amazing. Well, ladies, we're going to continue our discussion after we take a brief break, but I think it's a wonderful beginning. Christy, we're going to hear more from you along the way and then learn about progress in specific leukemias and also about clinical trials. Because when we talk about some of these newer medicines if patients hadn't been in clinical trials we wouldn't have those medicines. We'll understand what's available at Northwestern Memorial. So stay with us as we continue our discussion on leukemia with Dr. Olga Frankfurt and also with a very grateful patient, Christy Moore. Stay with us. 11

12 Types of Leukemia Welcome back to Patient Power as we're discussing the latest in leukemia and how it all comes together. An example certainly at Northwestern Memorial where they have a multidisciplinary team, and as Dr. Olga Frankfurt was saying just a moment ago, very experienced, skilled nurses and increasingly happier stories as we heard about with Christy Moore, newlywed, who just before her wedding was diagnosed with CML and how she then had one of the newer drugs that worked well but then a transplant which worked even better and no sign of the disease now. So that is the story we'd like to have for so many more people. Dr. Frankfurt, let's talk about this world of leukemia. So as we have said all along, leukemia is a cancer of the blood, and there are different types, and now you're identifying even more subtypes. So we also mentioned about the bone marrow. So the bone marrow is sort of the blood factory. Do I have that right? That's exactly right, yep. And so for whatever reason something goes haywire there and you're making, depending on the type of leukemia, defective cells. I always think of it like a copier machine that's kind of turning out pages with a streak down the side or something, but because the bone marrow is a limited space it can crowd out the other cells that you need for a healthy immune system, right? I like this analogy. Maybe I'll use it with my medical students in the future. But you're absolutely right. For whatever reason one cell becomes abnormal, and it cannot function the way normal white cells, it cannot mature like normal white cells do. It cannot fight infection. It s a very abnormal, immature, dysfunctional cell which only can reproduce, and it makes many more abnormal, dysfunctional, very unattractive looking cells and that they prevent normal cells from developing because they have this proliferative survival advantage. And given an opportunity they will replace the entire marrow, and frequently when we do a bone marrow biopsy on patients with acute leukemia or even chronic leukemia the only thing we see is identical looking, ugly, leukemia cells. Now, you mentioned about a bone marrow biopsy, and I've had a few and I know typically leukemia patients will. That's where you're taking a biopsy, a sample from where the blood is made, in the bone marrow, typically I know in the hip, and then that goes to the pathologist and you're trying to see what percentage are these kind of cells gone haywire versus the healthy cells and also looking at what kind of defective cell are you looking at. 12

13 That's absolutely right. I'm relatively young in my career, but even the number of years that I've been here every year there's new information becomes available. There are things that we are doing now that we were not doing two years ago and the things that determine the outcome and at this point even therapy. An example is acute myeloid leukemia with what we call a FLT-3 mutation. It's a mutation that we know is indicative of a very aggressive disease. Those people we typically attempt to take them to transplant right away as soon as they achieve remission. But right now there are novel drugs that attempt to inhibit this mutation, and they have been having a very promising, very promising results. And it's the second generation of those drugs. First generation did not work well at all, but the improved versions seem to be attacking the leukemia cells with this FLT-3 mutation very, very actively. Let's help people understand that. So you're looking at the cells from the bone marrow biopsy, and you're looking at which subtype. So what we used to describe as somebody with AML, as you used the example, AML was AML was AML, but now you're seeing, well, this is an aggressive subtype, this one isn't. This one responds to these medicines we have now, this one doesn't. This one someone will have to have a transplant, this one we might be able to use this new drug or a combination. Do I have it right? I could not say that better myself. And this information is literally multiplying every year, so we have to be very careful. We need to understand it better, but yes, you're right. There are molecular genetic characteristics that tell us a lot about the disease. All right. A note, sort of a Patient Power note for our listeners. In this field of leukemia, and I'm around a lot and I've been living with it for many years, it is moving very fast. And I have to tell you, and it's no put down to doctors wherever they are or cancer specialists, because imagine all the cancers sort of a doctor in a smaller city or smaller town may have to keep up with. But what Dr. Frankfurt gets to do is participate and stay up on the latest research for these leukemias that we're discussing, and it's moving very fast. And so certainly wherever you may be listening, whether in Chicago land or at a distance, you want to consult with a specialist like Dr. Frankfurt because you want to get the benefit of the most experience and the latest knowledge. And also the availability of trials that we'll talk about a little later. But the main point here, Dr. Frankfurt, is we're looking at kind of a range of diseases within these sort of categories of AML, CML, ALL, CLL, right? And then it's an individualized approach you take. 13

14 Absolutely. And that's the goal. I mean, that is the goal, and this will change in the next number of years. We will be refining things further and further, and that's why it makes it so important to have people to participate in clinical trials because the only way things will get to become a standard of care, the only way things will become FDA approved is if we actually can prove that our theories are indeed reality. You're absolutely right. I mean, I don't take care of breast cancer. I do not take care of colon cancers. The only thing I do is leukemia, so I try to know every little detail about the disease. And I understand, Christy, in your case this discussion of transplant, not only did you go other places but Dr. Frankfurt was consulting with her peers elsewhere as well. There was a discussion going on, a team, if you will, to see what was right for you. Yeah. No, I definitely remember that, and with Dr. Mehta. That I think is one of the great things at Northwestern is they can reach out and they have a great network. Right. And I think that's so important today. Well, let's talk a little bit about some of the specific leukemias, Doctor. Let's finish up on CML, since that's Christy's diagnosis, chronic myeloid or some people call it myelogenous leukemia. So she's doing great after transplant. There are many people now who take a pill every day. First there was imatinib or Gleevec, which was just a huge breakthrough, and then we now have more powerful medicines that are increasingly being used. You mentioned one of them, dasatinib, or Sprycel. There's Tasigna which if I get it right, nilotinib, I think Nilotinib. is right. And then at this last meeting, the American Society of Hematology, there's even discussion of later-stage drugs that maybe could even help a broader range of people with even more types of mutation. The jury is still out, but it seems like it's moving very fast. The landscape of treatment for CML is changing really fast. You're right. I mean, imatinib was truly a revolutionary drug. The thing about CML is that there is one main driving mechanism that we can identify while in other leukemias a lot more pathways are involved and a lot more things are abnormal, so it's very difficult to use a very targeted approach. But in CML you can. There are no novel drugs so some of the patients, when they are on the medications for a long 14

15 time they develop resistance to the medication. Cancer is always smarter than we are. It's always a step ahead of us, so we have to keep up. So there are medications that are available on clinical trials intended for patients who progressed despite being on the Gleevec or Tasigna and dasatinib drugs. And we're going to have that clinical trial open very soon. It's open in a number of cancer centers throughout the United States. Right. So people are on a journey, and, as you say, can you develop medicines to stay ahead of the cancer? Well, that's a good question, and we're trying to do that. Right. But many people now, let's face it, who a few years ago would not survive are able to take a pill and live well. Right now we have a different problem because most people have no side effect, they're doing very well, and a lot of people don't want to take their medication. You've got to remind them to take their medicine. They are doing so well and you have to draw a picture of how things were before the Gleevec and what was life expectancy is and what would inevitably happen. It inevitably would progress. There was no spontaneous remission. There was no disease going away. It will like a train it will progress, and the question is when. So we just have to remind people of that all the time. Right. You know, that's just an amazing story in medicine, where people would progress, and they would typically not survive, and now you can take a pill, feel so good you forget you have the chronic leukemia, and you start cutting back on your medicine, and you don't want the horse out of the barn for sure, so we have to remind people. Let's go on to the leukemia, really the most common adult leukemia, the one I was diagnosed with at age 45, and I know typically people are diagnosed in their 70s, chronic lymphocytic leukemia, CLL. And there too you have a variety of subtypes. There are some people where it never really goes anywhere, and there are other people where it can be quite aggressive. So again it's understanding the individual case, right, Dr. Frankfurt? 15

16 Absolutely. Absolutely. Again, we do various molecular analysis, chromosomal analysis that again statistically predict how a disease is going to behave. Now, nothing is hundred percent, and the most important thing is follow the patient and see what their disease is doing because granted we don't understand everything about the disease, but you statistically speaking with can predict who will behave how and what kind of therapeutic interventions would be needed. It can get very complicated. I've learned enough to be dangerous, if you will. They talk about, what is it, p53 mutations? That's right. And all these different things that they look at when you're diagnosed to say do you have what their experience has shown will be a more aggressive form. So, Doctor, let's talk about indolent or less aggressive form of CLL. Whether somebody is older or whether somebody is younger, it seems like you have a lot of options now to help them do well. Very true, and I'll probably use the word "overwhelming." When you go to the meetings like ASH, just the one I came from, there are so many new molecules, there are so many new things that are being explored in this condition that we will have a hard time figuring out how to sequence things. Because CLL is a chronic disease, meaning that without a bone marrow transplant we cannot cure the patient, which means, and I tell my patients look at it like you look at high blood pressure. You can't cure it, but for as long as you are on medication you should be okay. So you're giving a treatment, you're hoping for a very long remission, but you know that you have not cured the patient. You know that it will come back and at some point they will need something else. I know that you were in Dr. Keating's clinical trial, which I assume was fludarabine-based chemotherapy? Yes, what they call FCR. FCR, right. And I was one of the early patients. I'll do my plug for clinical trials. I had to put my trust in the team and the research, and I was early on in it, and I am very gratified that the treatment that I received 10 years ago in a clinical trial was 16

17 approved this year, 2010, and is now really sort of the gold standard worldwide, although it's a heavy-duty therapy and I know there's research going on and can there be sort of gentler therapies, if you will, that will help other people. Oh, but that's actually our approach here at Northwestern. Because we know it's a chronic condition, we are trying to use milder biological agents, maybe trying to avoid chemotherapy. But obviously we would like to achieve the level of remission as you can with chemotherapy so people can have many years of normal life not thinking about the disease and not thinking about getting treatment. But we are trying to use biological agents like Campath, rituxan, ofatumumab that just got approved frontline in chronic lymphocytic leukemia. Doctor, you know, I was younger with CLL, but most people are older, maybe in their 70s, but they deserve quality care too. It's not just you're older and you have a chronic condition, and you know, you just go about your business. You take it seriously in an older patient as well. They deserve options. Absolutely. I think my oldest patient with chronic lymphocytic leukemia, I believe he was in his mid 90s, and his disease was so dramatic he had significant swelling in his legs. He could not stand up. So when he came to my office he said, I cannot make a martini sitting down, so you have to, to fix my leukemia so I can make a good martini. So I actually had to give him, he had very aggressive disease, so he had very small doses of chemotherapy, disease melted away, and he was able to make his martinis. Okay. Well, that's the communication you have with your doctor, hopefully a specialist like Dr. Frankfurt, for your individual situation. Now, we talked about CLL and we talked about CML, the C meaning chronic. What about acute leukemias? There's ALL and often that could be in children but it can be in adults I know over 50 as well. And then there's AML that's often in more senior people. Where are we with those? So acute myeloid leukemia is much more common in adults. Again our understanding of the disease probably ahead of our ability to treat it, unfortunately, although outcomes in especially younger patients are much better nowadays than 10 years ago, 20 years ago. But we're still far from being perfect, and that's why it's so essential to be able to put patients on clinical trial with new promising drugs so they will become a standard of care. And in ALL? 17

18 That disease is difficult. Most of the information we draw from the pediatric population because there is no such thing as a pediatric private oncology, so all of the kids are going to the big academic centers to be treated for acute lymphoblastic leukemia, and most of them are enrolled in clinical trials. So most of our information we gain from the pediatric population because they are much better than adults to undergo clinical trials. So, yes, there are new drugs for acute lymphoblastic leukemia. There are new medications. There is improved understanding of the disease itself. So, yes, there is progress. Not as amazing as I would like, but there is definitely progress. Transplant I had a friend who was in her early 50s who had a transplant actually for ALL, and it came on really fast. Fortunately she had a twin sister who was a perfect match for her and she's doing really well. She's actually on one of the boards of the Leukemia and Lymphoma Society. Let's talk about transplant for a minute. Years ago when it was developed, you know, not everybody, maybe most people didn't survive the treatment. It was heavy-duty. Now we've come a long way. Where are we now with transplant? And I'll take you through the different types, Dr. Frankfurt, but just generally transplant as an option. Are we perfecting it? Absolutely. There's no question about it. You know, a number of years ago, age of 50 or age of 45 was probably a cutoff point for undergoing the transplant. Right now we can take people who are in good physical health in their 70s to undergo what we call a mini stem cell transplant. So I can elaborate on that. So when you do an allogeneic stem cell transplant, a stem cell transplant from somebody else, the reason it works is, one, you are able to administer some meaningful amount of chemotherapy that will hopefully wipe out whatever residual disease you've got. But also those donor cells, not only can they go into your bone marrow and repopulate and make normal blood and normal immune system, they also have ability of recognizing cancer cells if they're left in there and kill them. And it's called graft-versus-leukemia effect. So in older patients who for example achieve the remission, you're able to give them very small amount of chemotherapy just to prevent the rejection of the donor cells and then infuse those donor cells and allow them to finish the work of killing whatever it is you're looking at that is left. And our supportive care has improved dramatically, antibiotics, you know. Mitigation to help people go through the transplant if complications occur has much improved as well. 18

19 Wow. And I want to help people understand that. So when you develop cancer the thinking is your immune system didn't identify these first very few defective cells that kind of were stealthy and they got by the immune system, they fooled it, and then they multiply. So when you have this donor immune system, if you will, these hopefully are smarter, and what Dr. Frankfurt was describing is they can go do the job that unfortunately your immune system didn't do the first time. You're being given a stronger immune system from the donor. Did I get it right? I suppose you can say that, yes. That's the job that's not done by the chemotherapy and the job that is not done by your immune system. Yeah, that's fair enough. Now, one of the areas that's been really exciting because there's not a match for everybody is could there be very immature stem cells or progenitor cells that are found in the umbilical cord of a new baby where they haven't really gotten in all these subtypes, if you will, that could be harvested and made available for an adult who otherwise wouldn't have a match? And I know you've been involved in that. Where are we with getting these donor cells from an umbilical cord to help an adult? You are absolutely right. So there are various sources of the stem cells. Early on they would just come from the brother or sister, and now they can come from the unrelated donor. They can even come from the parent. Those are more experimental, but that happens, and of course the cord stem cell. So the umbilical cord that connects mother and a baby that usually is thrown away once baby is born, there are a fair number of those very immature stem cells that are able to do the job like over regular stem cells. So I believe it's about 20,000 cord stem cell transplants have been done since its inception. I actually met the man, at the time he was a little boy, who was the first one to undergo a cord stem cell transplant. His parents had another baby and they traveled to Paris, France, where the first cord stem cell transplant occurred. For adults you need two because very few cells are in there, but that is a good alternative. There are certain disadvantages about it that we are working on, on improving, but that's definitely a very viable source. If you think, you don't have to inconvenience the donor, although it's not terrible, but still an inconvenience to be evaluated, to have a blood draw, so if you can get it from the cords that would be much easier. Also the timing is an issue because it takes a long time to identify the donor, to collect the donor. You have to accommodate that person's schedule. With the cord, they're right there. They're sitting there frozen, ready to be used, so that's an important issue. 19

20 Because the cells are a little bit more immature than the regular stem cells that you get from a grown person it might take a longer time for the counts to recover, and that may translate into an increased risk of infections and some other problems, so it has not became the first choice but it's definitely making its way as more and more doctors become comfortable using those. Dr. Frankfurt, we've talked so much about things working out where people can live their lives, whether it's the chronic management of a leukemia or maybe be cured but at least do better. We have to point out that it doesn't always work out that way. Unfortunately, you are very much correct. Bone marrow transplant, for example is the most aggressive therapy we've got available, and in many cases the only curative options available, but sometimes the disease comes back even after patient undergo allogeneic, somebody else's stem cell transplant. There could be complications like infectious complications in what we call a graft-versus-host disease when the donor cells get a little confused and they attack not only the leukemia that is present in the bone marrow but some of the normal cells of the body, and we have medications to stop it but in a number of cases it could be lethal. So we have to be very careful who we select for the bone marrow transplantation. There are many other factors that can predict what the outcome would be, but there are certain things that we cannot control. So it's still a risky procedure. Not everybody does as wonderfully as Christy does, but very many people do. So we try to improve and do better and better so more people will go back to their normal life after the transplant. All right. We have so much more to discuss and we will. When we continue our program we're going to talk a little more about clinical trials because, as we said, I received treatment in a clinical trial 10 years before a drug combination was approved. And imagine medicine, Sprycel or dasatinib, that Christy received that was so meaningful for her, if people hadn't been in clinical trials it would not have been available. And there are a lot of clinical trials at Northwestern, and we'll hear more about that. So stay with us as we continue our discussion about leukemia on Patient Power. We'll be right back. Clinical Trials Welcome back to our discussion about leukemia with Dr. Olga Frankfurt, a specialist in leukemia at Northwestern Memorial. And we're also going to hear more from a woman who, I'm betting, she'll say that Dr. Frankfurt and the team saved her life, and that's Christy Moore. We'll be back with Christy in a minute. 20

21 Dr. Frankfurt, I mentioned clinical trials, and I was in one, a phase II clinical trial. So if I get it right about a phase II, so phase I is trying to understand in humans is the drug safe, right? That's right. Phase I are the safety assessment. Okay. And phase II is what is the effective dose? That's right. Efficacy assessment, right. And then phase III is then testing it with a bigger group of people after you think you sort of have it figured out but you want to always look at the safety and the effectiveness. So for me, I benefitted from the drug combination that's widely used, FCR they call it, the acronym for the three drugs used in CLL, and I received that 10 years before. That's a long interval, but the point is whether it's in any of these areas you have a number of clinical trials that you're doing at Northwestern. So when somebody comes in and they're newly diagnosed is that part of the discussion? We have this approved therapy and we have that one and sometimes we do transplant and let's take a look at your individual situation, and then you see, well, are there trials that should be part of the discussion? So the way I always tell my patients is that the only reason I would have a clinical trial open, either write one myself or open trials written by one of my colleagues or even by drug companies sometimes, if I believe that this drug or this clinical trial will answer a very, very important question. And another criteria for me to open a clinical trial at Northwestern, whether I would be comfortable to enroll myself or my family member on this clinical trial. And if the clinical trial passes those two criteria then I open it, and then I offer this to my patients. I always explain to the patient how we do clinical trials. So let's say the idea of some medication comes up and we try it in the lab and we try it in the animal and we decide that this does make sense. It looks promising. It looks interesting. We're going to try. So phase I clinical trial, the medication is typically to offer to the patient who failed everything that is available, and if it has any activity in those kinds of patients then this drug will move on to phase II clinical trial. And only if the drug has been showing promising activity in phase II clinical trials, only then it would move into phase III clinical trials. And in phase III clinical trials the patients never get placebo. Patient will get what standard of care is and as a second arm would be a combination of what the standard is with this new drug. So I always explain to the patient that the worst-case scenario, even if they don't get the drug they will get what the standard of care is today. 21

22 One of the things I liked about being in a clinical trial too besides the prospect of getting tomorrow's medicine today, if you will, is I got a lot of attention. I mean, I spoke regularly to the research nurse, the clinical coordinator, and I felt like I was getting the best of the best. Not that people who aren't in trial don't get very quality care, but I liked all the attention. You know, when I went to an exam there were maybe more people in white coats in the room, but I felt special, if you will, and I felt like I was helping other as well. Well, I think leukemia doctors in general are pretty obsessive and pretty much hands-on in the care of their patients because there are so many things that could go wrong, and when they go wrong they go wrong fast so you really have no time to, you know, get a phone call tomorrow. It all needs to be figured out immediately when the patient has some kind of complaint. But you're probably right. On the clinical trials there is this extra step because we're studying a new drug. We need to make sure that we not only help people but we don't hurt them because there are a lot of clinical trials and not all the drugs make it all the way through, meaning some of them are not beneficial. So we always have to think of that, and we always have to make sure that we do not hurt the patient. Closing Comments All right. Let's go over some points we've been making along the way, and that is, first of all, and I really believe this so strongly, ladies and gentlemen, that if you're diagnosed with a leukemia today I believe you should at the very least have a consultation with a specialist like Dr. Frankfurt because it's a fast-moving field. Second of all, you want to make sure that the diagnostics, if you will, that come into play like we talked about, the expert pathologists who are looking at bone marrow biopsies or studying your blood or even from the physical exam where you saw Dr. Frankfurt knew by poking Christy's spleen she had a really clear picture of what was going on, and that's the wisdom that can come into play. You want that brought to bear for you. So I urge you, wherever you may be listening, to have a consultation with a specialist in leukemia and also, like we just talked about, where they're also doing clinical trials so that can be discussed to see if, if you feel comfortable and your doctor does, does that line up with your personal situation. Dr. Frankfurt, I want to give the last word to Christy, but before we do, just to sum up, you are a younger doctor, but even in your time practicing you've seen tremendous changes, haven't you, and where do you think it's going to go during your career? 22

23 Well, I think we will be able to cure many more forms of leukemia and subtypes of leukemia as we do now. I don't know if we'll be able get them all in my lifetime, but we already cure a number of subtypes of leukemia, and I think that number will increase. And if I may add to the second opinion portion that you mentioned, we do this in academic medicine. We do it all the time. There are difficult cases that do not fit the textbook behavior, and very frequently I ask my colleagues at the University of Chicago either through the pathologist to review the bone marrow or my colleagues at the University of Chicago to clinicians to look at the patient. So, you know, I feel very comfortable doing it, and many, many people do. I very much encourage people especially when the cases are difficult to seek a second opinion just to be evaluated. And you do second opinions as well. Absolutely. Absolutely. We frequently get people from pretty much anywhere in the country come for a second opinion, absolutely. All right. Well, I want to wish you all the best in your career so that we can do this interview in a few years and we're going to tick off these different leukemias and you're going to say most people are cured, most people are cured, and then you're going to tell me how you're going to retire and play golf somewhere or go on a long sailing trip. But now there's a lot of work to do, but I want to thank you for all you do, Dr. Frankfurt. It is my pleasure. The reason I do it is because we have the most amazing, really, most amazing patients. Oh, well, let's go back to one of them. Christy, so you've been married three years now. You've been listening to this discussion. We've retold your story. We're going to hear about those kids hopefully in just a few years. What do you want to say to Dr. Frankfurt as a representative and maybe your lead on the team that is really giving you a new lease on life? What do you want to say publicly? Well, to Dr. Frankfurt and the whole team at Northwestern, when you're diagnosed with cancer your life is completely turned upside down, and all you want is to know that you're in the best care possible, that you're getting the best and the most advanced treatment that's available. And across the world we looked, and at Northwestern, from the ER doctors knowing to do more tests on me, to take a 23