myeloma news live from the international myeloma workshop...

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Myeloma News LIVE from the International Myeloma Workshop, Kos, Greece.

Webcast June 29, 2007

Brian G.M. Durie, M.D. Beth Faiman, R.N., M.S.N, C.N.P. Maddie Hunter

Please remember the opinions expressed on Patient Power are not necessarily the views of Millennium, our

partners, or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own

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Introduction Andrew: Hello and welcome to our special webcast bringing you the very, very latest information on multiple myeloma. I'm delighted to be here. I'm way over in the Pacific time zone in Seattle, but with great help from our friends at the International Myeloma Foundation, Susie Novis, and great financial support from Millennium Pharmaceuticals, we're able to take you way over to the other side of the world, to Kos, Greece, where for the last week there's been the 11th meeting of the International Myeloma Workshop. They meet every two years, and this year have brought together between 16- and 1700 people, world experts all talking, researchers, nurses, doctors, and some patients who are very involved and want to bring you the news too. So the goal of today's webcast, which is the first in our series of seven hour-long live webcasts, and there will always be a replay and a transcript that you can get on patientpower.info and often it will be linked from the IMF myeloma.org website so lots of ways to get to it. We will be answering your questions as we can, but today's goal in particular is to really get the perspective of a leading patient advocate, whom you'll meet in a second, a leading myeloma expert and a leading nurse practitioner who specializes in myeloma on what they thought is significant for you, the patient, the family member, the friend caring about multiple myeloma and in the thick of it. That's what we want to bring you today. A Patient Advocate’s Perspective Andrew: So let's go to Greece and get the headlines from our panel of experts. First I want to introduce you to Maddie Hunter. Maddie is normally in Metuchen, New Jersey, but she's been spending time now in the very hot weather of Kos, Greece, over a hundred degrees many days. But, Maddie, you've been living six years with multiple myeloma, you've sat through these sessions, and you’ve mingled with experts from around the world. Just the headline of your impression on the significance of this meeting for people living with myeloma.

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Ms. Hunter: Well, thank you so much, Andrew, for the opportunity to share this. The first thing that I wanted to say is that there are other 50 countries of all those folks you just identified here, and, you know, the biggest impact to me as I joined the meeting was just seeing the collaborative worldwide effort to get us closer to a cure. So some of the things that stuck out for me ,and I'm sure we'll get at lots more of these, but some of the first headlines, there are lots more options for the front-line patient, the newly diagnosed patient, lots of things that had been initially in the refractory and relapsed phase that are now moving forward. So there are lots more options for those that have been newly diagnosed. And I think one of the big news items is that there are now more steroid-free options being trialed and used that include some of the novel agents that we all have been hearing about, Velcade and Revlimid, with others that are new and are keeping us from having to completely rely on the steroids, which for patients brings with it a lot of side effects. I think some things that stuck out for me personally, there's a phenomenon I heard about called Bringing Them Back, which is some of the folks that have had many, many treatment protocols and has potentially had exposure to some of the drugs that we're now hearing about, Velcade is an example or Revlimid, we're finding that there's combinations of some of these drugs that for people who may have had some resistance to them early on in their journey with myeloma are now able to use them again with renewed response. So I think that is exciting. I happen to have some renal insufficiency so my ears really perked up around some of the research I heard that suggests that there are some combinations involving Velcade that actually can reverse the adverse impact to kidneys. So I think that's great. I think there's a product in the wings for bone support. Many of us take Aredia or Zometa as bisphosphonate support to our bones. There's something in the wings such as self-injectable compound and I think it's called, and Brian is going to help me with this, but AMG 162, which potentially is going to give even more freedom to those of us who are needing that. So those are some headlines. Andrew: So, Maddie, taken together as you depart from Greece, and I know you're going to be traveling around Europe and sort of digest all this and as you fly home, are you encouraged? Ms. Hunter: I never come away from these meetings without having incredible hope and encouragement. Not only do we have many more options but the whole world of genetics is pulling us closer to understanding how to personalize therapies. I think that there's just so much good news. And, frankly, the dedication and commitment

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of folks that I see who are collaborating across boundaries of countries and languages to really devote themselves, I mean, I have goose bumps. Highlights of Meeting from an Renowned Expert’s Perspective Andrew: Thank you. Now we're going to meet two of the health care providers who are part of that group who devote themselves to people living with myeloma. First let's meet Brian Durie. Many people know him. He's the chairman of the International Myeloma Foundation. He's a renowned myeloma specialist worldwide, but he practices at the Cedar Sinai Comprehensive Cancer Center in west Los Angeles. And also he is the co-chair of the myeloma subcommittee of the Southwestern Oncology Group. So that's a group that does clinical trials. So he's very much involved in not only treating people but also doing all sorts of clinical research and very active nationally and internationally. And, Brian, some headlines from you on the significance of this meeting and what it means to patients today. Dr. Durie: Well, thank you, Andrew. I really appreciate the opportunity to convey the thoughts and the feelings coming out of this meeting. This is a five-day meeting which has literally run from morning to night, 8:00 in the morning and some of the sessions running actually close to midnight with the opening session, so a really intense meeting over five days, with different formats for presentation. Satellite sessions, oral presentations, poster sessions. And perhaps what I found most interesting, an innovation of this meeting, debates, where two experts would debate a couple of the most important questions. Perhaps I can start with that. The two debates which occurred were, one, how important is it to undergo very aggressive therapy to try to achieve a complete response, and what will be the impact of that long term? And the other, which is the first time that this has really happened in about 20 years now, is it essential for all patients to have a stem cell transplant, one or perhaps two with the advent of the novel therapies? For the first time the results are so good with some of these novel combinations that many experts are thinking that perhaps a particular combination could be equal to or possibly better than stem cell transplant results. So this was unique and reflective of the impact of novel therapies. And so we heard in those different kinds of sessions, including several hundred posters, details focusing at the first level on the three novel drugs that we have had now since 1998. We have thalidomide, we have, obviously, Velcade, and most recently we have Revlimid. And so, as Maddie mentioned, the first question has become, How do we use these drugs optimally for the newly diagnosed patient? What is the impact of using them along with dexamethasone?

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Or, as Maddie mentioned, most interestingly, how about steroid-free up front, using something like Velcade Doxil or with the low-dose dexamethasone? This is an area of particular interest because of the results from an Eastern Oncology Group study presented and discussed in a variety of settings. The combination of Revlimid with dexamethasone one day a week versus dexamethasone four days, three pulses each month. So I think everyone was excited to see not only that the one-day-a-week dexamethasone was much less toxic as we certainly anticipated, with a much lower risk of DDT and other kinds of side effects, but actually was, if anything, better than the higher dose dexamethasone regimen. And the results were compared with the Velcade combinations, Velcade Doxil, where you actually don't take any dexamethasone at all, as well as Velcade dexamethasone maybe using intermediate doses. So the focal point for those discussions was how is this impacting the early survival for patients with myeloma. And for me this was amazing. Because I've actually been to each of these biennial meetings, the 11 of them stretching over 22 years, and so this was the first time that there was such an enthusiasm that we are actually having excellent survival right from the outset. Ten years ago using melphalan prednisone and some of the chemotherapy and even some of the early studies with transplant, unfortunately 20, 30 percent of patients had serious problems even within the first year. But now we heard 98 percent of patients living and in remission at the end of the first year. So a huge improvement where the immediate threat of the disease was not well, people talked about it's not a death sentence any more. 98 percent of patients are alive at the end of that first year. So really a transformation in the way that we're looking at this disease. And then after that do patients need to have a stem cell transplant? Really a very close debate on that. Very, very interesting discussions. And then with the advent of the very new therapies, the completely new therapies, new proteasome inhibitors, even drugs beyond Revlimid, the relapse patient has so many options which might ultimately move up front. So those were some of the high points for me. Andrew: Wow. I can just say wow. And while I live with a different cancer I know from my friends with myeloma, and we heard Maddie, and I know folks are hanging on every word. What you're really looking for are cues whether you should be encouraged, and, Dr. Durie, I really hear that from you. I can imagine you're starting to go to these international meetings when you were about 14 years old, Brian, because you're still a very young man. But thank you for your devotion to this. We're going to get more of the details as we continue.

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A Nurse Practitioner’s Perspective I want to go to Beth Faiman. Beth is a nurse practitioner at the Cleveland Clinic. Beth, you're devoted to oncology patients. You're devoted to myeloma patients. People call you. We talked about this steroid-free idea, but certainly many people have been on therapies that have included steroids, and so there are the side effects. You help people through it. You were listening carefully, I'm sure, as a nurse practitioner as to how can we help people get through therapy, lower side effects, raise quality of life. Was it encouraging to you what you heard? Ms. Faiman: Oh, absolutely, Andrew. And thank you again for having me. I just wanted to mention and echo the sentiments of Dr. Durie and both, Maddie. Most of what was shared with us, the thought leaders from all these different countries working together on a common cause. You know, the side effects of therapies are the biggest concern. Dr. Rajkumar had shared with us from the Mayo Clinic some information on a trial that decreased the dose of steroids in his regimen containing linalidomide. And this is a huge impact, because I think we're starting to see that steroids don't need to be in the regimen. We already know that Velcade is a very effective therapy as a single agent and can work even better with steroids, but I think identifying the best regimen with the least toxicities is very important. And in addition to that I know some thought leaders were sharing ideas of how to select therapies. Currently we take a patient's age, and we take their kidney function, and we take a few factors into consideration, but we're really not taking into account the side effects of the disease that have caused them maybe less of a good quality of life. So what we're trying to figure out now is how can we do functional scores? Take into consideration the patients in many different factors when we're trying to select a regimen and really tailor it towards them. I was really impressed at a few of the things I heard here such as the new agents targeting myeloma bone disease, such as what Maddie had mentioned earlier. Subcutaneous administration of Velcade, there's really, really early studies and that's going to be a huge impact on patients and their quality of life, not having to come to the clinic as often for a wonderful regimen. I think that there was just a lot of information shared, and I'm sure we're going to go into details in this call, but it was a very exciting meeting overall. New Research on Velcade & Bone Formation in Myeloma Patients Andrew: Well, if you're excited, we're excited. So that is good.

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But, Maddie, you're living with it. I just want to go back to you for a minute. You know, we mentioned about the effects of the disease and some of the treatments on your bones, and that is a worry long-term, especially when there was concern about some of the side effects of even medicines that might deal with that. And I'll ask Brian this too, I think there was some news about Velcade at least related to it being maybe positive for the bones. Is that right? Ms. Hunter: Well, actually that was something that was--I don't know if it was a brand new announcement, but I picked that up in the conversations that I heard in one of the presentations and validated it with Brian, because I wanted to make sure that I heard correctly and there was some sign that Velcade definitely helps with the bone formation, which, you know, in a sense makes it even more magical as a drug. Andrew: Did you want to comment on that, Brian? Dr. Durie: Right. Absolutely. This came up at a number of sessions, as you were implying, Maddie. This was something that we've become aware of over the last two or three years, but the information was kind of consolidated at this meeting. A couple of observations. Some time ago the group in Little Rock, Dr. Zangari, working with Dr. Barlow, he had noticed that in the Velcade treated patients there was an increase in the alkaline phosphatase, which is an enzyme that comes from the bone when the osteoblasts are active. So there was a unique observation here that the cells that promote bone healing were actually activated along with the use of Velcade. And this was subsequently confirmed by Dr. Gregory Mundy, who was at that time at the University of Texas in San Antonio where in laboratory studies he showed that directly Velcade does stimulate the osteoblasts which are responsible for bone healing. So there are now studies looking at that clinically. And it was a small report but there were little nuggets of information scattered through this meeting. And so there was a report documenting actual bone healing in the skull and spine of his patients receiving Velcade, and it was actually the first time that I had actually seen that documented with x-ray and CT scan findings. As most of you probably know, although we can shut down new bone destruction with the bisphosphonates that does not necessarily trigger the new bone healing. So this finding of new bone healing is very exciting. Research on Combining Novel Agents Andrew: Let me ask you a question as sort of an observer of this. So it sounds like there is now an active debate about where do the novel agents come in versus transplant.

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Dr. Durie: Right. Andrew: And that's healthy. And so that's an exciting thing. And I know there's a lot of research going on and, Maddie, you and I had talked about before the program about into the genetics, and we're trying to understand which sort of subtype at the genetic level do you have of multiple myeloma, which therapies or combination therapies are going to be right for you so we can have the most targeted therapy, the longest, healthiest life, high quality of life and hopefully a cure. So that's very important. But in the meantime right now we're developing new uses of these novel agents, I think, as the foundation of care. And what I heard you saying, Brian, is some of these agents that have been used for people who are relapsed are now moving forward, which is typical in cancer care as you have exciting new agents. And I even saw something out of this, too, where maybe there's even research into combining novel agents. Where do we stand? And maybe you could comment on the newest approved combination, too, which I guess would be Velcade Doxil. Dr. Durie: Right. So obviously that was the most recent approval indicating the added benefit in terms of response and very recently the impact on survival of combining Doxil with Velcade versus Velcade. So that's exciting both because it works and also because it's steroid-free. We also heard, though, about the combination of Velcade with new agents. A couple which are kind of at the top of the list, one is combining Velcade with the heat shock protein 90 agents, and there is in fact a randomized trial starting later this summer to look at Velcade with or without this heat shock protein inhibitor. And there are other combinations like that with both Velcade and Revlimid combining the kind of documented novel agents with the truly new and not fully tested novel agents. Andrew: And didn't I see somewhere the idea of combining Velcade and Revlimid? Dr. Durie: Yes. There's particular interest in that because you have basically there the two most powerful recently approved drugs actually, the two most powerful drugs for the treatment of myeloma. And this has been an interesting evolution where, yes, they are the most powerful, yes, they are the most highly active or synergistic in the lab. In other words, you get the most dramatic benefit with anything by combining those two particular drugs together. However, it is actually a little bit delicate to figure out the best way to combine them, because, for example, both

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drugs do cause reduction in blood counts, and so some dose adjustments are required. And there has been some question about, well, with Revlimid there is some risk, increased risk of deep vein thrombosis or blood clot problems, whereas with Velcade that's not an issue. And so if you bring the drugs together do you need to take aspirin or a blood thinner or is it safe to exclude that? Fortunately, Revlimid doesn’t really cause neuropathy so that's not an added risk of bringing the drugs together. So I'm actually personally excited because I'm looking towards a new Southwest Oncology Group trial where we will be comparing Revlimid plus low-dose dexamethasone, what I call Revlidex, with the combination of Velcade plus Revlidex. Detection. So we're really, really excited about the opportunity to see the impact of that combination which we think will be very, very effective. Future of a Cancer Care Acronym for Myeloma Treatment Andrew: Brian, one other question for you. So while many people go to a myeloma specialist such as you and such as Beth at the Cleveland Clinic not everybody does, and so the rest of the world and the community oncologists are kind of looking to you all for leadership, and a lot of it comes down to in cancer care kind of acronyms, you come to bring together as you do combinations. In lymphoma there's this acronym CHOP. And so I know you've spoken to me about could there be a new CHOP acronym or that sort of thing in myeloma? Where are we with that? What would be part of it? Dr. Durie: Well, that is a really exciting area. And when you're bringing drugs together, and there does get to be kind of a limit in terms of toxicity that you can accept when you bring two drugs, three drugs, and perhaps four drugs together. I think it's mostly accepted that probably it's tough to go beyond four, although occasionally we do. So we're looking at maybe three or four drug regimens. And the CHOP that you mentioned was obviously four drugs. So there is an idea to combine two older drugs which would include in this case a steroid, a low-dose steroid, so low-dose dexamethasone, with an alkylating agent, so of the old drugs, melphalan or cytoxin would be the most powerful that we have. Obviously, melphalan at a high dose is what we use for transplant. And then many years we've used the VAD regimen, which is based upon adriamycin. And so the new variation of adriamycin is Doxil, which is a long-acting form of adriamycin, so that would be a third drug. And then of course the fourth drug could be Velcade and so that you would have a combination of Velcade, Doxil, cytoxin and dexamethasone as a new kind of a CHOP regimen. And that's one example of a type of combination that really could be dramatically effective.

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Andrew: So one other question for you, Brian, and then I want to get to Beth and Maddie too. And that is it sounds like with these novel agents now, Velcade is a good example, becoming for more people the foundation of care and not just where these drugs have started, for previously treated people who have relapsed, but moving forward. Dr. Durie: Well, maybe I'll just make a brief comment about that. I think it's a matter of tailoring. Although we can't completely individualize the main thing I'm seeing, and I will be interested to hear Maddie's perspective, is the impact of age. And I think this is much more of an issue in Europe where this has been a basis for treatments decisions for some time. And so that for patients, and we kind of arbitrarily select 65, patients over the age of 65, we're looking more to less toxic regimens, simpler regimens. And so the standard of care for the older patient has become melphalan, prednisone plus thalidomide, and that combination is very effective. And we're now looking at new variations of that, perhaps melphalan, prednisone plus Revlimid, for example, or melphalan, prednisone plus Velcade. In the front line setting by contrast I think that this is a positioning where Velcade leading into stem cell does have a strong position. And in that setting the major concept is a Velcade regimen plus stem cell, how does that stack up versus perhaps an IMiD regimen, which may or may not involve a transplant. Andrew: The way I see it is - I'm a person who does weird analogies sometimes, but maybe it helps people. And that is I think you all have a lot more furniture in the room. You have a lot more notes on the piano. You know, you have a lot more things that you have in front of you, spread out, that have effectiveness. And you're trying to see how do you move them around and which tools are used for which person. We don't have that yet. I think from what I've read though, Brian, it sounds like related to Revlimid and Velcade, certainly, Velcade very broadly, that you do have that, though, that works for most people. Like, Maddie, you mentioned earlier about your concern about renal insufficiency in people with renal problems. So you have some good tools now that can work for most people, but obviously you want to target that even further. Dr. Durie: Right. So Velcade is good in patients who have renal compromise. And also, interestingly, because of the lack of risk of clotting, DDT problems, Velcade is a very good choice in the setting where there is a concern about that particular problem as well. So, as you say, a lot of good, good pieces of furniture that you can move around depending on the scenario.

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Andrew: And I know a lot of work going on to see what's right for who. Go ahead please. Options for Older Patients Ms. Hunter: Andrew, I wanted to just dovetail on what Brian was saying about options for the older patients. I was really struck with, I think it was Dr. Palumbo from Italy who was presenting on whether there's a place for high-dose therapy in folks that are, elderly is defined differently in different settings, but it sounds like the elderly is 65 or over. But the point that he made that I thought was so compelling is that there's a call for more trials on the difference between biological age and chronological age, that we have up to now been potentially limiting what's available to the elderly patients because of this notion of chronological age and what it implies and that it does not fit everybody. But there are cut-offs for trials that are very specific to age. And so I was very encouraged that Dr. Palumbo opened that door. And I don't know whether there are trials like that in the works, but I was encouraged to see that we're looking even more flexibly on how we define the options based on age. Dr. Durie: Absolutely. How to Discuss New Research With Your Doctor Andrew: Beth, I want you to give us a little coaching. So there you are, you're at one of the most prestigious clinics, the Cleveland Clinic, and people are going to listen to this program live or the replay, a whole series over the next several months, and they're going to hear from experts such as yourselves, and the news. And then they're going to say, Oh, I got to talk to my doctor. I've got to talk to my nurse about it. And, of course, we're still trying to learn what's right for each individual. How should somebody begin this discussion? I mean, you can't go in like a bull in a china shop and say, I heard Dr. Durie say X or I saw this press release and I've got to do this. I mean, how do you have this discussion about what's right for you? Ms. Faiman: Well, that's a great question, Andrew, and I get that asked all the time. First of all, I'd like to try to encourage the patients to try to have an open relationship with the doctor or the nurse that is treating you. You need to have trust, and that trust is easily damaged if they're not willing to listen for you. We have so many resources, patient support groups. We have the wonderful International Myeloma Foundation. There are so many resources, and it's not uncommon for somebody to come into my office and have a little printout of what they saw on the internet. So that's particularly helpful for me because as I stay up to date I think on most things that

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are in the works I'd like to see what the patients are reading. So if you have a question, and you wanted to print that out and take it to the office and take that into your provider or your nurse, and then you can have an open discussion. And most people will know what you're talking about. The other concerning issue is side effects of therapies. Dr. Durie was mentioning Velcade, for example, peripheral neuropathy. This is very easily treated, for example, by being, again, open and communicative with your nurse or your doctor that cares for you. Dose modifications will allow you to complete your therapy, for example. Also other problems such as side effects, risk of infection, you have to weigh the risk and the benefits, and we're really making strides to create this myeloma as a chronic disease. So, again, getting back to answering your question, Andrew, any kind of information you have and the International Myeloma Foundation is an excellent resource. They can help direct you and get the literature that you can take to the office. And for the most part a good, educated practitioner will listen to you and help answer your questions specifically. Andrew: Great answer. Thank you. We're going to take a short break, and we will be back. But I want to give the phone number for the International Myeloma Foundation hotline, if you don't already know it. 800-452-CURE. 800-452-2873 between 9:00 a.m. and 4:00 p.m. Pacific time, my time zone. 800-452-2873. We'll be right back and take your questions, and many have been sent in. And continue our discussion with patient advocate Maddie Hunter, Dr. Brian Durie, myeloma expert, and nurse practitioner Beth Faiman, calling us all the way from where the news was made in Greece. We'll be right back with more Patient Power. Remember now, you want to discuss your personal situation with your doctor or with your nurse to see what's right for you. And that's what we're trying to figure out as a worldwide group. Both our discussion today the 16- to 1700 people who braved the heat in Kos, Greece for a week to really show their devotion to all of us who are living with cancer. And, certainly, Brian has said previously to me, learning is going on in myeloma that may have impact on other diseases too. Transition in Focus from Front-Line to Sequential Therapies So, Brian, back to you. So other studies you'd want to mention? It seems like we're kind of in this time of thinking, Okay, we've got these established therapies and we know their effectiveness. You mentioned melphalan, there's been thalidomide, certainly dexamethasone. How do we build on that, or in transplant too, or at what point do we switch away from that. So we're kind of in a transitional time, aren't we, Brian?

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Dr. Durie: Absolutely. I think that the other broad concept that relates to that is we've really been focused on the front line therapy and then stem cell transplant as a way to go. But now the discussion was perhaps with these drugs which are so effective in controlling the disease, it is so much closer to being a chronic disease, that we can look at sequential therapy. So we can actually be anticipating a long survival, and we're sort of pacing our therapy choices to the disease. So we're anticipating that we can give a combination which will produce an excellent response which will last for a number of years, but then we also know that after that can use another cocktail that can again give a response and maintain the disease in a good clinical state for a further number of years. And so this concept of sequential therapy and making myeloma chronic on the way to hopefully accomplishing a cure I think is a major conceptual change. Advice For Maintaining a High Quality of Life After Treatment Andrew: Now, we got a question exactly about that. And, Beth, maybe you can help us. James from Grants Pass, Oregon writes, listening to all this, "What are questions I should be asking my oncologist or oncology nurse? I'm active. Should I continue to play tennis and golf?" So I take it James is trying to have that high quality of life. How can they have that discussion? Ms. Faiman: Well, that's an excellent question as well. I get that all the time, and the big thing is that people years ago only lived a shorter life span, and now people are living many, many years. And people will always say, "How long am I going to live? I say it's not very fair to answer that question but by continuing to be active in terms of exercise and I don't restrict people. There are many factors that you need to consider. Number one, though, do you have damage to your bones from the myeloma? Myeloma likes to affect the spine, and most people at diagnosis oftentimes will have bony involvement. So the first question I'd like to have him ask his provider or his doctor is what do you think, how strong are my bones? Make sure that they don't twist the spine in many cases. And a very good therapy that I recommend to my patients is water therapy. It has very little resistance on the bones. It can still help rebuild bones, but you're putting yourself at less risk of damage. So that's the one question in trying to maintain an active lifestyle. And tennis is oftentimes a low enough impact that we do not restrict people, especially if they don't have widespread bony disease. But exercise, and there will be a big study that's coming out of the University of Arkansas that's still kind of in the works, but looking at exercise in multiple myeloma and improving quality of life, because we all know we feel better when we

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are more active. So really that's the big thing here is do I have damage to my bones, what is the status of my bones, and am I putting myself as risk if I continue to play tennis, or golf. I have a lot of golfers too. Andrew: I think the image of, yes, it's terrible if you've had a diagnosis of a cancer but it can go--not only go about your life but just enjoy it with zest. Ms. Faiman: Absolutely. Andrew: Play a sport like that. And, again, you know, I want to say that 70 is the new 50, whatever. So these age things and I think you all, Maddie, were talking about it. What's really the biologic age of somebody and how active are they. That's changed tremendously. The Role of Pain & Follow-up Testing Dr. Durie, here's a question for you. It comes in from someone named Chung. And Chung, it looks like his wife is going through a lot of therapy, and while I know it's not fair to someone to say do this or do that--we can't practice medicine over the internet--here's the question. He writes, "After Velcade replaced Thal-Dex my wife hasn't felt any pain associated with myeloma. Does it mean that she's winning a battle against myeloma?" So is pain any kind of measurement of success against the disease? Dr. Durie: A very, very important sign. I think that pain is one of the main manifestations of myeloma. Patients experience pain as there is bone involvement. So this is very, very encouraging. Although I think that as physicians we want to double-check that you are indeed winning by checking the myeloma protein level. We like to make sure that the myeloma protein in the blood or myeloma protein in the urine is going down proportionately and that we are really making the kind of headway that we want to make. And so I would be encouraged but also encourage follow-up testing to make sure things are indeed moving in the way we want. Andrew: Now, you mentioned about measuring the protein. So people have bone marrow biopsies, and somebody wrote here they said, Well, there hasn't been measurable protein in their urine, so how else would that be measured? Dr. Durie: Right. Well, this is increasingly a concern or question, and I don't understand why, but we do see more patients where the protein levels are very low or there might

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actually be no protein in the blood or the urine even although there has been evidence of new myeloma. And so then we are forced to use some newer tests. And two things I'll mention. One is the use of the new blood test, the free light test. And this measures the amount of free light chains in the blood. And about 70 percent of patients who don't have any measurable myeloma protein in the blood or urine do have elevated levels of these free light chains in the blood. And so this is an additional test that can help us to monitor the disease in that setting. For the 30 percent of patients where this is still not showing anything we may need to do a follow-up bone marrow, which can obviously be helpful, but myeloma is a patchy disease so we need to do follow-up imaging which could be x-rays, MRI of the spine and pelvis or possibly even a whole body PET scan or CT PET scan and try to pick up whether there might be sites of disease.

How to be Educated About the Latest Thinking Related to Myeloma Andrew: Okay. Now, Maddie you hear this, and so I ask this question, how do you take up all this with the doctor. We hear Dr. Durie talk about new kind of tests. It's not on every street corner and not every oncologist knows about it. So how do you counsel people--and you run a support group--so that they can get the benefit of the newest, latest thinking related to myeloma, and that includes testing methods as well as treatment and side effect management? Ms. Hunter: You know, one of the ways that we support people within our particular support group, and I know this is true across many of the support groups, is that we have an education thread throughout all of our discussions. So we will make sure that the literature that the International Myeloma Foundation has available is on hand so that folks can understand and learn from reading. We have speakers that come in to educate our folks about what the options are to measure and to track their disease. And another thing which I think is really important is that patients practice with one another talking about how they're going to raise issues with their physicians. I think one of the things that I love about our support group is that we have a lot of peer mentoring that goes on where, you know, someone might be reluctant to ask about what tests are available to help track their disease or they don't understand something about their particular disease. And raising it first with a fellow patient in a safe kind of context and then rehearsing how they're going to raise that often makes a difference in someone really having the confidence to be able to go forward and have the conversation that Beth was saying is so important to have.

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Dr. Durie: Right. Perhaps I could just comment on that. Just to be clear, I think that you would agree with this, Maddie. We obviously very, very much want patients to continue to work closely with their doctors, and there's a blend between that where occasionally depending on the type of question there might be a need for an additional opinion. But the first starting point is to work closely with your doctor and work through perhaps some new testing or new treatment. And if it's absolutely necessary it may be really important to get that extra external opinion. Andrew: Right. And I'll just say in my own case I was in a clinical trial, and I had that team of the local community oncologist working with the subspecialist who I'd paid a visit to, and that actually led to me being in a clinical trial. And I was in the kind of guru doctor's clinical trial, but it was executed by my local oncologists, and they were all learning together and I was in the middle and it helped me. Dr. Durie: Yeah, that's ideal. If that works out and there's a good friendly interaction, that's really the way to go. Ms. Hunter: And I think, Brian, you certainly are stellar in how you offer second opinions. And I think that one of the things I find in some newly diagnosed people is the reluctance to ask their doctor to go for a second opinion for fear there will be some insult, some, you know, bad feelings generated, which might ultimately result in poor care for them. And this has just not been my experience with physicians. Although I'm sure there are examples of this. You know, I love to keep telling people that that is a standard practice and that physicians, certainly myeloma experts are very willing to provide that second opinion and work closely with local community doctors to ensure that the right care is given. Ms. Faiman: I just wanted to briefly add to Maddie's point. Working at the Cleveland Clinic, it's not easy to navigate the large hospital system, and we really do not mind. And, as a matter of fact, I think it will be better overall for the quality of life of patients if they can feel comfortable saying, Gosh, this is a wonderful therapy. Can I get this at home? And do you think this is in my best interest. And, absolutely, if there's one thing you take home from this call today find out if there's any way that your local doctor can work with the larger referring doctor. Dr. Durie: Absolutely.

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Clinical Trials & Older Patients Andrew: Yeah, that's something I wanted to bring up and not just from the perspective of the patient who may in myeloma--not always. Maddie, you're a younger patient, in your 50s and I was younger, in my 40s for leukemia. But often we have family members who are listening now and we got a question like this from Tom who is in Valparaiso, Indiana, and he's concerned about his father who is 78 years old. And what he really wants to know about is how can he find a clinical trial that might be right for his father. And then, Beth, I'd say the second part of it is, besides finding it, how can he help his father feel comfortable with a clinical trial and know that that could possibly give him tomorrow's medicine, tomorrow's combination today. You know, just make a one aside, because this is really for me. I have a friend Amy, her father was diagnosed with multiple myeloma, oh, I guess it was about six years ago or so. Velcade was in trials, and he just didn't want to face it, you know. And yet when he finally was open to the Velcade trial, and we know how Velcade worked out, could have been life-extending for minimum, you know, it was too late. And so how can we find the trials for our loved ones and how do we have the discussion with them to help them feel comfortable if it's appropriate for them? Beth? Ms. Faiman: Well, this is also very common of a question. I oftentimes will suggest to folks go to websites. We have a myeloma hot line which is a wonderful resource, and you can log onto it at 2 a.m. if you can't sleep. And in addition we have the myeloma website, the myeloma hot line. And we have a clinicaltrials.gov which will also direct you towards what clinical trials are available. The second thing is to become educated about the diagnosis. IMF has so many patient education materials available so that you can really educate yourselves towards the diagnosis. And this is probably not finally but my third point would be patient support groups, local chapters in which you can gain information. Maddie is the leader of her support group, and oftentimes she had mentioned about the patient mentoring and that is just a huge valuable resource. You don't have to be a patient to be mentored, you can be a family member. So in your community you can call up and say, Gosh, what are my centers of excellence, and you can be linked in many cases toward somebody there who can answer questions. I'm oftentimes getting questions called into our hot lines at Cleveland Clinic and I would suggest these same things so that you can feel comfortable.

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And how do you talk to Dad at the age of 75 who just wants to sit at his house and not necessarily face the diagnosis? Again, by being educated about it and sitting down with the family members. Ultimately, it's his decision, but we can give him the tools and do the leg work. And maybe that's what it is, he doesn't want to feel comfortable doing the leg work. But if you help him out by doing that background searching and pair him up with maybe another patient who's on similar therapies, then you can have a very successful outcome in many cases. Ms. Hunter: Andrew, can I add something? Andrew: Oh, sure, Maddie. Go ahead. Sure. Ms. Hunter: I wanted to say that I think that in the case of how do you encourage a parent or a loved one to be willing to join a trial, I think the important thing is to find out what it is that is getting in the way of them wanting to consider it. And sometimes it's a fear. There's this notion that if you're in a trial you're going to be a guinea pig, and that has a negative connotation in many people's minds. And when you become educated about what it really means to be in a trial and the stellar care and in some cases the extraordinary care that you get in being monitored and watched and cared for in trials takes care of that kind of concern. My father also had myeloma, and at the stage that he had myeloma he was not a candidate for the trials that were available to him, but he and I had a lot of conversations about whether in fact he'd be willing. And, he, you know, at a certain age was just in this mindset that it was not a safe process. And I think he got to the point where he would have been willing, but I think Beth's comment about support groups being useful, having Tom bring his father to a support group so his father can talk with others that are his age who may have had the experience may also be another possible way to help him. Andrew: Right. Great point. Brian, I just want to make one point. So you're at this international meeting and you hear data come out from studies. Well, somebody participated in those studies, and you're seeing some truly exciting results, you know, extended survival, better quality of life. Well, those people got the benefit of that by participating. Dr. Durie: Absolutely. Well, I think that one important aspect that I'd like to emphasize is that right now we are incredibly fortunate that we do have approved drugs on the market and available for patients. So, for example, we have Velcade and Revlimid

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which are both approved new drugs and so that for many patients these wonderful new drugs are available and can be prescribed by the physicians and can be in many cases the excellent first choice. I think that for a 78-year-old it could be that having one of those combinations could be an ideal way to go. Now, obviously, if that treatment is not working we do have excellent trials, and I agree with all the comments that have been made about that. But I think that right now we are extremely fortunate as compared to the past where excellent treatment can be available without necessarily being in a clinical trial. Andrew: That's a great point. That's a wonderful position that we're in now and that we're looking at a long term in chronic illness. And one thing I want to pick up on that you said was you're finding that there are drugs that can be--they sort of pooped out a little bit as an individual therapy, but you're able to have combinations now, and given synergistically they can be effective. Right, Brian? Dr. Durie: Absolutely. And it might be that would be a situation to consider a trial where one drug has become less effective, and that may be the situation to consider the trial and follow through on the comments and suggestions that you just heard. Post-Transplant: Recommended Drug Maintenance Therapies Andrew: Okay. Now, there are people listening who certainly had transplants. So are there certain drug maintenance therapies that you're recommending, Dr. Durie, based on what you've heard there, post transplant to help people be well for a long time? Dr. Durie: Well, this is, interestingly, another very, very hot topic for discussion because there have been trials. The most recent one up for discussion is the use of thalidomide as maintenance, and particularly the French but also the Italians have been looking at the use of thalidomide as a maintenance agent. And so there is evidence that taking thalidomide as a maintenance, low dose after a stem cell transplant can prolong both remission and survival. However, the interesting point which leads to the discussion is that this benefit is predominantly for patients who are actually not in a full remission. So actually the patients do have a little bit of myeloma left after the stem cell, and the patients who benefit are actually ending up taking the thalidomide as an additional treatment. So it's not so much a maintenance as--we're not sure what the right word would be, maybe consolidation--but certainly an extra treatment which pushes the disease down to a lower level and maybe achieves the complete response.

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Because the additional point beyond that is that there is this notion of a treatment-free interval where you could actually be off treatment. And so one very, very wonderful option and potential for myeloma patients is that they can get into a fantastic remission and maybe have a block of several years where actually they don't need to be on treatment. And perhaps Maddie, you would wish to comment on that. Ms. Hunter: Well, I'm sort of living proof of the possibility of there since I was one of the fortunate ones to have a complete remission coming out of my transplant. So I've been treatment free for many years. And the quality of my life is, you know, I've enjoyed wonderful opportunities as a result of that. Andrew: Yeah, that's the idea. Certainly, there are pills and different medicines somebody might have to take on a daily basis. I imagine there's an advantage if you can just go on with your life and feel the cancer is at bay and just go on. And Maddie, you've been experiencing that, correct? Ms. Hunter: Yeah. I'm so grateful and I feel very fortunate. You know, it sits with me, the notion is not an absent thought for me. I mean, myeloma is definitely a very present realty for me. It sits on my shoulder, and every ache, every extended cold, anything that's out of the ordinary makes me wonder is this my moment for relapse. But, yes, I've been very, very lucky. Dr. Durie: So it's a blend of attempting to achieve that versus try to go find a therapy which has minimal side effects that might maintain things for even longer. Andrew: Right. One comment just while we're there. Beth, about whether you want to call it compliance or adherence, Maddie has been fortunate that she had Velcade, right, Maddie? Ms. Hunter: No, actually, I've not been treated, Andrew. Andrew: Oh, okay. Ms. Hunter: I've not had a treatment.

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Andrew: You've been very fortunate that you haven't needed it. Some people have had Velcade and then gone on and had sort of a treatment-free interval. But for people who need to take a medicine regularly or stay on a therapy, compliance, is that an issue, just helping them stay with it, Beth, and understand the benefits of it? Ms. Faiman: I think so, Andrew. And when you think of taking a pill every day, one of the biggest complaints I get is somebody will come into my office and they'll be on 10, 12 different pills. Their primary doctor puts them on pills for this, I put them on pills for that, and it gets to be a real bear. And sometimes people will not take their pills. Other people view it as, I'm doing something for my disease. The one thing that I have a concern about with maintenance therapy, and Dr. Durie did mention this is a hot topic, in thalidomide we have extensive knowledge, and in lower doses the peripheral neuropathy is probably one of the biggest side effects. Again, peripheral neuropathy is pretty much characterized by you have some numbness, tingling, burning in the feet or hands, or sometimes it's just a numb sensation. That's my one concern with long-term thalidomide use is you can develop this neuropathy. And thalidomide, again, is an oral pill, and it's very effective, and it's good as well in different combinations. But one of the things that we are concerned about if you have a pill that will be on it every day--Maddie has experienced this wonderful holiday, where she hasn't had to take anything, but oral pills every day will lead to compliance issues. But then again you have this cumulative side effect, and you don't want to eliminate future options. And I know I wasn't asked specifically, but one thing I wanted to mention during this call is there are a lot of treatments that are emerging and studies relative to peripheral neuropathy. But I would encourage you to really keep up to date in how you're feeling in your hands and feet, and can I button my top of my blouse and am I using my hands and feet properly. Because it can be a big problem down the road with these newer agents that might have similar side effect profiles. Andrew: We're going to get some final comments from each of you and just go a couple of minutes over. Thank you for sticking with us folks. And remember the replay and the transcript will all be on patientpower.info probably by Monday, just before the July 4th holiday if you're listening in the U.S. What Myeloma Patients Should Take Away From the Meeting Beth, so a final comment to you. You've made this trip to Europe, to Greece, braved the 100-degree heat. So when you go back to Cleveland Clinic or even as

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an advanced message now, what do you want to say for people living with this condition or if they have a loved one who is? Ms. Faiman: Now more than ever there are so many exciting combination therapies, single therapies, more cocktails that we never even dreamed would be possible. Multiple myeloma, and I hate this phrase, used to be called as an orphan's disease. And I think they still call it that, but I don't think it's an orphan anymore. We have so many great therapies, and the side effects are manageable. If you can just communicate your disease and your concerns and your thoughts with your nurse and your doctor and really be aware of what to report, these things are manageable and people can live a very long good quality of life. Andrew: Okay, Beth. And we wish you a safe travel home. So, Dr. Brian Durie, you've been devoting your life to this. You are integral to the International Myeloma Foundation, great partner for today's program and thank you for that. Brian, you'll be flying home, and as you go you have a lot to digest, but it sounds like you are a very encouraged guy, and we have more and more to offer people. Dr. Durie: Absolutely. Such a positive, positive meeting and I think a couple of things. One is that we have increasing precision from all these different new pieces of information. We can give more accurate advice for our patients. If you take thalidomide or maybe Revlimid as a maintenance how much benefit could I anticipate from that versus possibly staying having a treatment-free interval and maybe using it later, so that we are in a position to give more precision to these discussions. But I think that most of all we have so many options now that we truly are to the point of having myeloma be a chronic disease for many, many patients. We can't say that will be the case for every patient, but I say probably for a majority of patients that we're looking at a chronic--an ability to control myeloma for many, many years. Andrew: Thank you, and I know you're a key part of that. I hope you get to do it. I hope we start curing people, Brian. Dr. Durie: Absolutely. Absolutely. As Susie says, If we have chronic, can cure be far behind? Andrew: Yeah. That's the big positive, see. That's right. And there's a lot of information, by the way, on myeloma.org the International Myeloma Foundation's website and

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comments further about Velcade and combinations there and about Revlimid and how the newer agents are playing such a key role for people with relapsed disease and also, increasingly, front line. And Maddie, you're our representative there, and you've been blogging about it, living with it. So you get the final word. Ms. Hunter: For once I get the final word. Andrew: There you go.

The Power of Education & Information Ms. Hunter: I just want to dovetail on everything that's been said about the power of education, the power of information and the wealth of options that we have to learn what's happening in this amazing field that is moving at the speed of light. And as I sit in all of these sessions and I struggle every minute to try and absorb and understand what I'm hearing what I don't have trouble getting is that the pace of change is so fast. And I sort of want to steal something that Ken Anderson finished our meeting today with. He quoted, and Brian probably can tell me the full name of the woman he quoted. It's Francesca- Dr. Durie: Thompson. Ms. Hunter: She was involved with the IMF at some point. Dr. Durie: Yes. It's a lady who was an orthopedic surgeon who wrote a book, yes. Ms. Hunter: And what's her last name? Dr. Durie: Thompson, Francesca Thompson. Ms. Hunter: Okay. So here's the quote that she said. This is about curing. She said, "Cure" and I think she was really mentioning myeloma when she said this "Cure is growing old and dying from something else." And I really feel, taste and see that as a possibility. And six years ago when I was diagnosed I would never have thought I

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could have really believed it. So I want to pass that hope and inspiration and encouragement on to everybody who's listening. Andrew: All right. Wonderful, exciting news. I want to thank Maddie Hunter, patient advocate; Dr. Brian Durie, from the International Myeloma Foundation, myeloma specialist; and Beth Faiman from Cleveland Clinic, nurse practitioner, for calling in now almost ten o'clock at night there after a long, hot but exciting week. Thank you all three of you for being there, and we wish you safe travels home. Folks, remember that on July 19th we're going to be very actively doing our Ask the Expert webcast, just like this but all questions. We think we're going to have Dr. Robert Orlowski from the University of North Carolina, another noted myeloma specialist. And then there's a whole series, so take a look at the special edition page on patientpower.info. Send us questions and be sure to take a look at that schedule, look for updates. And we'll be back with much more, six more hours. Okay. Thank you so much for joining us today. We wish you and your family the best of health. And remember, knowledge can be the medicine of all. Andrew Schorr signing off.

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