More Effective Treatments for Multiple Myeloma Convention Connection: American Society of Hematology Meeting December 2010 Dan Vogl, M.D. Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. Please have this discussion you re your own doctor, that s how you ll get care that s most appropriate for you. Andrew Schorr on location in Orlando, Florida, at the meeting of the American Society of Hematology. There are thousands of doctors and researchers from around the world here. Front page news in their daily newspaper is multiple myeloma and all the progress that s been made this year, or the last couple of years, and the prospect of a lot more to come. We got an overview of all this news from Dr. Dan Vogl from Penn Medicine. Dr. Vogl, let s start this way. People are newly diagnosed with myeloma. Maybe they ve never heard of it. They re terrified of the diagnosis. But here we are at this point in time. It sounds like you have more tools than ever before. How would you describe it? So I think it s very clear right now that, for someone newly diagnosed with myeloma, there are a lot of treatment options. Our biggest challenge is deciding which ones to use at which point in the course of the disease to maximize the benefit that we can get from them compared to some of the side effects that we can see from them. So it s very clear that we have a lot of options and a lot of really good treatment options and a good prospect for good responses and long lasting responses that can give people many years of good, quality life. Of course, the question comes up when someone is diagnosed, however that may happen, how do you know what you re dealing with in that patient and when you need to start treatment? So, there are a lot of people who are diagnosed with asymptomatic myeloma, or what we call sometimes a smoldering multiple myeloma. There certainly is a lot of interest in starting treatment early and getting the disease under control before it causes any symptoms. Although, I think at this point, we still don t have any good data that says we should be starting treatment in patients who have no symptoms whatsoever from their multiple myeloma. 1
So what we do as part of the evaluation is a careful look for any evidence that the myeloma is truly causing problems. If we find any conclusive evidence that it s causing problems or that the problems are coming up very quickly, that s our indication to start treatment. There are ongoing clinical trials of treatments for people who are truly asymptomatic. But I think right now, outside the context of the clinical trial, we don t have any good reason to start treatment in someone who may continue to have no symptoms from the disease for many years after their initial diagnosis. Now you do a lot of testing when somebody is newly diagnosed. Certainly at Penn you take a very complete look at them. So it s not just one disease, right? It s various subclasses. I think it s very clear, both from what we know about the biology of the disease and from our clinical experience, that we really are dealing with a number of different diseases when we talk about multiple myeloma. There are some tests that we can do that distinguish between some subsets of these diseases, like the cytogenetic testing that we do that tells us, really, whether the biology of the underlying disease is different. Then a lot of what we do is look at people clinically. We see how they re doing and how they respond to therapy and how their disease changes over time, with or without therapy. That tells us a lot about how they re going to do in the future as well. All right, let s talk about these drugs. At this American Society of Hematology meeting over the last few years, it s almost been dizzying the data that s come out on newer medicines. So where are we now with approved medicines and their use, either alone or in combination, giving benefit to patients? So we have, I would say, six or seven approved medicines, three that are probably truly considered new: thalidomide, lenalidomide and bortezomib. Then older medicines, like steroids, dexamethasone and prednisone, cyclophosphamide, melphalan and doxorubicin that also are very effective, especially when used in combinations. Then coming out, there are really many new drugs that have a lot of promise. The closest to clinical use are the newer generation novel agents carfilzomib and pomalidomide. But right behind them are several more that hold a lot of promise for really providing benefit to patients. Okay, let s talk about that for a minute. So the excitement over the last few years has been two groups of medicines, proteasome inhibitors and these so called IMIDs. So you 2
mentioned thalidomide and lenalidomide, Revlimid. Then there s bortezomib or Velcade proteasome inhibitor. So tell us, do these work the same or can they work in combination? What s the concept in fighting the cancer cell? So these two classes of medications work very differently in attaching the multiple myeloma cell, as do our older, more traditional chemotherapy agents. Even more than working differently attacking the myeloma cell, they also have very different side effects for the patients. So it s become very clear that it s easy to combine them, in terms of side effects for our patients, and much more effective to combine them. So that you can see better responses when used in combination than when used as a single agent for any of these agents. Okay, in looking ahead, I know there s a, perhaps even approved in the next few months, it s up for consideration, is carfilzomib, which would be a second generation proteasome inhibitor. I believe there s another IMID that could follow lenalidommide, maybe a little further down the road. What would be the advantage of these, yet, newer generation drugs? Carfilzomib is a second generation proteasome inhibitor so very similar in the way that it works to Velcade. It s also very clear that it s an effective medication, like Velcade. Probably the biggest advantage that we re seeing in the clinical trials so far is that, unlike Velcade, which causes, as one of its main side effect, a neuropathy or damage to the nerves, which gives patients numbness, tingling and sometimes pain, carfilzomib doesn t really seem to cause any neuropathy at all. So, while we re still learning where it s going to fit into the overall range of treatments that we have for multiple myeloma, it certainly seems like it s going to be an interesting and useful option for patients who can t tolerate Velcade because of the neuropathy. The new IMID, or immunomodulatory drug, pomalidomide, which is closely related in structure to thalidomide and lenalidomide, appears to be particularly interesting because it seems to be very effective even in patients whose disease has stopped responding to the other two drugs, and especially to lenalidomide, or Revlimid. So with the very encouraging response rate, even in patients who can no longer receive the other medications because they re no long working for their disease. So for someone who s on a journey, hopefully a long journey, with myeloma, it sounds like you re having more lines of therapy where you might start here but, if that is no longer working for you, you have something else. 3
Well, you know, we used to think that was had, maybe, two or three lines of therapy to offer any patient with myeloma. But in the clinic now, I think we re routinely seeing that we can treat patients with 8, 10, 12, 15 different lines of therapy over the course of the disease, tailoring each one to the individual situation of the patient in terms of what prior responses they ve had an what prior side effects they ve had from the various treatments they ve received so far. I want to pick up on the second thing you said. Obviously, job one is beat the cancer. But the other is let someone go on with their life, hopefully, with little or no side effects. Side effects from some of the earlier drugs have been not insignificant. So how do you manage that? And what is the importance of communication between the patient and their doctor so that those side effects can be identified and limited? So I think that we have been learning a lot about preventing some of the side effects from our multiple myeloma treatment. Probably one of the biggest areas that we ve learned about is the peripheral neuropathy, or nerve damage, especially from Velcade. What we ve learned is that if you identify that early and make adjustments to the treatment regimen, especially spacing out the doses of Velcade, you can often avoid the worst of the neuropathy symptoms. We found that you can then get people through treatment, eventually get them a full course of treatment with Velcade and a true benefit to their disease. It s really important, therefore, that when patients are going through treatment that when they notice side effects that they let their doctor know immediately so that their doctor has a chance to modify the treatment regimen in ways that can allow it to still be very effective against the disease but minimize the side effects that they re going to get from it. One other area I wanted to ask you about. You re at an academic medical center. You re involved in a lot of clinical trials. So with this landscape changing, newer drugs coming along it looks like, but are all in clinical trials everything has been in a clinical trial it would seem like, at least at your center, that would be part of the discussion. Is there a trial that might be right for me, particularly if I ve gone through other therapies on myeloma? Well, we include clinical trials as part of our treatment options for patients at all stages of their disease. So in our current and upcoming menu of clinical trials, we have options for patients who have asymptomatic myeloma, patients with newly diagnosed disease who have not gotten any therapy, patients who are considering going through a stem cell transplant and patients who have relapsed, or refractory myeloma, who have been through many treatments already before. 4
For any of those patients, a clinical trial is an option. They should carefully consider whether going through the process of the clinical trial might be of benefit to them or help provide information for future patients. Because that s really what helps us move our knowledge of myeloma along and move towards eventually finding a cure for this disease. One last thing. Relating to a cure, there s a headline in the newspaper here for doctors who are attending sessions, as you have, in myeloma at this conference about whether you can identify the stem cells where all this comes from and, basically, shut them down or, basically, where the cancer doesn t develop. What s your thought about that, this cure or hope? Well, the idea of finding that myeloma stem cell, or the cell that has the potential to regenerate the entire disease and is thought to be resistant to a lot of the current treatments that we re using, is a great idea that I think we re still working on figuring out. So there are clinical trials going on looking at specific medications that we hope might hit those very resistant, very slow growing cells that eventually cause relapse in our patients. So I think participating in clinical trials is a good idea for that right now. But right now, we don t have a treatment that will truly do that. Okay, so they re describing it in the paper as the Holy Grail. You haven t quite found that yet. No, I don t think we have. But that s it. For someone living with myeloma, newly diagnosed or living with it, it s a much more positive time. I think it really is. I think we have so many treatment options, even just among those approved and available for current use. Then the number of new and encouraging treatments coming down the line is even more hopeful. Thank you very much. You re welcome. 5
Truly a very positive and ever-changing landscape of treatments for people diagnosed with multiple myeloma. In Orlando, I m Andrew Schorr. Please remember the opinions expressed on Patient Power are not necessarily the views of our sponsors, partners or Patient Power. Our discussions are not a substitute for seeking medical advice or care from your own doctor. Please have this discussion you re your own doctor, that s how you ll get care that s most appropriate for you. 6