News from ASH: Updates on Lymphoma and Other Blood Cancers ASH Conference Coverage December 8, 2008 Andrew Evens, D.O. 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. Introduction Hello, this is Andrew Schorr broadcasting live from the American Society of Hematology meeting in San Francisco where we ve been meeting with leading experts, and now it s our chance to meet with a lymphoma specialist from the Robert H. Lurie Comprehensive Cancer Center of Northwestern University, and that s Dr. Andy Evens who is a lymphoma specialist there. He s also at the Feinberg School of Medicine of course, and he made a presentation just moments ago really on more aggressive B-cell lymphoma. Dr. Evens, welcome back to Patient Power. Thanks for having me Andy. Great to see you. Thank you. Okay, so tell me first of all, you ve been dealing with one of the more common lymphomas. Tell us about your research and really what the significance is as we better understand this illness. Yes, it can be complex at first because there are many different subtypes of lymphoma, and even talking to other doctor colleagues sometimes they don t appreciate that there are more than thirty different types, and so often when we do research we don t just generically look at lymphoma, we go by which one of the 30 specific subtypes. That s usually meaning under the microscope diagnosis, and the presentation that we just had was on the most common subtype of the thirty different types, diffuse large B-cell lymphoma, which is an aggressive lymphoma but is thankfully treatable and curable in most patients, not all. All right. Now first of all, let s just review. How is it typically treated now? The standard therapy in terms of treating it is usually a combination, not usually, but the standard is rituximab which is now about ten years old with chemotherapy, a regimen 1
called CHOP, C-H-O-P. Each letter is a different chemotherapy, but it was shown about five years ago that when you add this rituximab, targeted therapy, it goes right to the lymphoma cell, increases the cure rate by about ten to fifteen percent, and so as of today, 2008 in December, the standard is rituximab plus CHOP. One of the things though that people have been looking at is, is there a way to get away from CHOP-based therapies, right, that might be easier to take? I think that s a good point, and that s a future goal, although I ll tell you, it may be in the future as we get more targeted therapies, but with CHOP therapy it s pretty well tolerated; it s all as an outpatient, and you usually get six treatments every three weeks. Of course we d love not to have to give chemotherapy, but right now if we took all comers, and certainly there are all kinds of patients; older patients, younger patients, and some sicker ones; but if we took all comers and looked at a thousand patients with rituximab and CHOP, we d probably cure around sixty to sixty-five percent, whereas before rituximab it was a good ten to fifteen percent, and so it s good, it s progress, but we look to one hundred percent, so we re still at a point where I think we re building on that. In other words, Rituxan and CHOP as a backbone, and I think the at least current strategies are not add more chemo. I think we re kind of maxed out, so to speak, on chemotherapy. We have other new targeted therapies, and I think it s going to be adding these targeted therapies to the rituximab/chop. Maybe in the future we ll be able to avoid chemotherapy but at least not in the real near future. Research in Newer Agents and Treatment Options Okay Andy, let me understand this now. There s a lot of research that gets presented here, and then if you wind around the exhibit booths there are all these pharmaceutical companies talking about newer drugs they have in later stage trials. When it comes to lymphoma it sounds like there s a lot of work going on. So you talked about newer, targeted agents. What from a research point of view shows promise? The good news is there s a lot. It s kind of good and bad news but much more good news. The bad news is, well it s not really bad it s just challenging because there are a lot of agents, and we have to figure out okay there s only so many clinical trials to go around, so that s where what we talk about translational medicine meaning we spend a lot of time with our scientists in the laboratory saying, okay you have this promising agent, this promising agent, it could be ten to fifteen promising agents; which are the best to test? And there are a few, and it does depend on which subtype of lymphoma. 2
There are some new antibodies that some people might say are new and improved rituximab. Then there are other antibodies that target different parts of the B-cell. Rituximab targets something called CD20, so there are some others that target different parts of the outer part of the cell, but then there are other therapies that target genes inside the tumor cell, so really, really ultra-targeted therapy. I ve been doing interviews on different illnesses, and I ve been hearing about newer medicines that hit the outside of the cell, target the cell, but just as you said trying to get inside the cell. So to really cure disease do you need that one-two punch if you will? Different modalities? I think that s part of it, but ultimately not only every cancer is different, every lymphoma is even a little different, and so it really, it may be one day in many decades we ll get to a point where it s just one treatment, but all these cancers are so different it really is tailored towards that specific cancer or even that specific type of lymphoma. Then really it s taking all these exciting, new, novel targeted drugs, and first you d like to know okay by itself does it work? You d like to have that signal. Does it work? And then once you figure out okay by itself it works, let s start combining it. Is it first safe, and then of course is it effective? If it s RCHOP, rituximab/chop, can we add it? Is it safe? And then does that increase the cure rate, and it goes through all the different levels of the clinical trials; phase-i, phase-ii, phase-iii; but it s that combination of translational research and then into the clinical trials, that s how we make the progress. It s always something we obviously talk to patients a lot about is that they re not guinea pigs or anything like that. It s how we make the progress. We re trying to take therapy that s good and make it great. I just want to mention. You may remember Andy that I m a chronic lymphocytic leukemia survivor, and I was in a phase-ii trial, and that was for drugs called fludarabine, cyclophosphamide, and rituximab used together in CLL. I received that in the trial eight years ago, and in chronic lymphocytic leukemia there was European data, phase-iii trials that validated that as really recommending it as standard therapy. So I m a big fan of clinical trials. I totally understand, and that s a great example, because back eight years ago we knew about fludarabine, but we didn t know, okay what if you add Cytoxan to it and what about rituximab, and obviously the goal at the time is improve outcome, have patients as most as possible go into remission and stay there for as long as possible, and that s exactly right. At the time we didn t know, but now we know, yes, those three together are pretty darn potent. 3
I like to say I got today s medicine yesterday, eight years ago, and I ve been enjoying it. Now it doesn t always work out that way. I d recommend people though seriously consider at an academic medical center like Northwestern a conversation with someone like you, is a trial a reasonable option at least to be discussed? I think that s a great point because I could say if it s not Northwestern or the University of Chicago, for almost every single tumor type, whether lymphoma or other cancers, there s a clinical trial, and like you said, what the clinical trials are really in essence trying to do is trying to say what s tomorrow s treatment. Be ahead of the curve. We re hopeful. There s a lot of exciting treatments out there. We re going to take a quick break, and when we come back we ll ask some more specific questions on how you can get the lymphoma care that s right for you and understanding what s being offered at Northwestern and the Robert H. Lurie Comprehensive Cancer Center at Northwestern University. We ll be right back. And we are back live on the Patient Power website www.patientpower.info and you may be listening to the replay in the IHealth area of NMH.org or on the Robert H. Lurie Comprehensive Cancer Center website. However you get it we re visiting with Dr. Andrew or Andy Evens who is a lymphoma specialist at Northwestern and also you re an Assistant Professor, right, with the Feinberg School of Medicine. Yes. But lymphoma is what you do, so let s talk about that. Unfortunately some lymphomas have been increasing in their incidence, but it sounds like you have medicines, there are many subtypes, but for some of the more common subtypes you have an array of medicines now, and many people can live with lymphoma rather than die from it, and so we ve been doing a lot better. We ve talked about all these candidates for study. So we have Rituxan, or rituximab, that was a big breakthrough for many lymphomas starting as you said ten years ago or so. Is there sort of a son of rituximab coming or other therapies or will there just be, as you said, other targeted therapies layered on top of it? I ll tell you, rituximab in retrospect was almost if not a home run a good triple, and we re looking for more of those. I think there are a lot of doubles and singles out there, but there s a whole list, and I ll give you just an example. There s a drug called bortezomib or Velcade that actually first received approval for multiple myeloma, a blood or bone 4
marrow tumor, and what s really interesting especially with these targeted therapies we often find that it gets approved in one malignancy but through that translational starting in the laboratory research we test it in other cancers, and it s a perfect example of where just about a year ago we got approved, bortezomib, for mantle cell lymphoma, particularly difficult to treat, and now we re looking at bortezomib in other subtypes; in follicular lymphoma and diffuse large B-cell. There are other examples. There are drugs called thalidomide or Revlimid, again approved for multiple myeloma and Revlimid MDS where all of a sudden wow, they look active in multiple different subtypes of lymphoma, and those are nice because they re oral drugs. So that s one way. Now sometimes it just all comes out for lymphoma. There s a class of drugs called HDAC inhibitors. There s one that s approved, an oral HDAC inhibitor. Again, a lot of these are targeting genes of the cancer cells, and that s where that translational research comes in because first you have to figure out, okay what genes, what s the literal DNA of the cancer cell, and then once you figure out, and obviously there s a lot of DNA and genes, do you have a drug to target it and to kill it? So very, very targeted therapies, and HDAC inhibitors are just one example of that. There s a drug that s approved to treat cutaneous lymphoma, but now there s a whole host of those drugs that we re looking in just regular types of lymph node lymphoma. I heard a presentation about Syk, S-Y-K? What is that because that seemed to show some activity in lymphoma? Yes. So similar concept. Syk is, just like HDAC, is a gene so to speak in terms of the cancer cells, Syk is another gene or DNA inside the cancer cells that what happens is normally in someone who doesn t have lymphoma your body recognizes these genes that like to make cells grow, and it turns it off, but what happens in lymphoma is something happens and they stay switched on. Syk is one of those that we found in different types of lymphoma, and Dr. Jonathan Friedberg at Rochester presented this at the plenary session yesterday that number one it s switched on in many different lymphomas, and they have a drug that basically targets that, and in several different subtypes; diffuse large B-cell as well as CLL; that it looks pretty darn promising. Coordinating Care with a Specialist All right, so there are people in Chicago-land who get a diagnosis of a lymphoma and maybe after they pick themselves up off the floor they begin to learn it s this subtype or that subtype, and then they say well is there anything new? 5
It sounds like first of all you have some standard therapies for many that are quite good, and in trials there are additional therapies that are very promising. Absolutely, and it really runs the gamut that almost any lymphoma whether it s newly diagnosed or relapsed there almost always is an option, and again whether it s trying to replace chemotherapy by just working by itself or sometimes we re adding it to chemotherapy and all different strategies. So yes we really recommend to all patients look at the options, and a lot of times we ll find that option, and we can work with the local doctor in getting a patient some of this new and exciting therapy. That s what I wanted to talk about next. Now some people might say, well I m beating a path to NMH. I m going to be down there. It s downtown, that s where I m coming, and they want to sit across from you, and others say, Well I have my local oncologist, and I live further out, or maybe at quite a distance but want to have a consultation with you either personally or want my doctor to. You re very open to that. Of course. We love to work and have a lot of good relationships with the community oncologists, and it s not just Northwestern. In Chicago-land we re lucky to have multiple, really excellent academic centers, so almost no matter what -- west, north, south part of the city -- there s an academic center there that at least at a minimum what are my options? Sometimes it s important because your future options, depending on the lymphoma, maybe not right now, it might not be valid, but at least you can almost start planning for the future. Not that you want to think about a relapse or something along those lines, but you like to know what are my options now and in the future? Right, it sounds like, and I saw this in leukemia, is it s worthwhile now. Hopefully your cancer will at the very worst be chronic. You want it to be cured, but if you can live with it at a very low level that you need a blueprint for now but also in the future and a pathway so that you don t close your options off. That s important, and when I meet patients, depending on the lymphoma, we ll often subdivide into two general groups. One group of lymphomas is more chronic, more indolent, but it is more chronic. It s very treatable but usually not curable, whereas another subgroup is very aggressive, it can be fatal, but yet it s curable. So especially for that initial group where we know it s more of a chronic disease, yes we don t like to burn bridges if at all possible, and sometimes there s a strategy that we try to set up and try to come up with; okay, don t burn the bridges. Start with this therapy, and think a little bit ahead of the time. It s real important. 6
All right, this is great information. I love talking to you, Dr. Evens. We ve talked before, and it just becomes so clear to me. I want to recommend to people though, I really want to underscore this, if you agree, and you can hear the applause, we ve got a lot going on here at this ASH conference It s exciting. Yes it is. I mean we have 30,000 people here from around the world, cancer specialists, if you hear clearly what is going on here that there are changes going on; a lot of thinking and more to come; then it s very important if you re diagnosed with a condition like one of these lymphomas to have some member of your team be somebody like Andy Evens who I like to say you eat, drink, and sleep this. We really do. I mean this is what you do. I do nothing else but lymphoma. Yes, so I think that would be something that I d really, and it can be lifesaving for people, so I really want to urge that. Assistant Professor Andy Evens from the Feinberg School of Medicine and the Robert H. Lurie Comprehensive Cancer Center at Northwestern University, thanks for being with us once again on Patient Power. I wish you all the best Andy with your research and thank you for all the care you give patients. Thanks for having me. Thank you too Andy for all your ambition and help with all this. Thank you. Well it s my pleasure. This is what we do on Patient Power, and I hope you ll tell others you know who may be affected by lymphoma or family members there will be a replay of this program; we ll be adding a transcript, and certainly we ll do followup programs with Dr. Evens and other members of the team at Northwestern. Reporting live from the Muscone Center here in San Francisco and the 50 th annual meeting of all these hematologist oncologists I m Andrew Schorr. Remember, knowledge can be the best medicine of all. 7
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. 8