Dr. Guido Tricot, MD, PhD, Holden Cancer Center, University of Iowa Interview Date: July 12, 2013

Dr. Tricot discusses his investigation into ways of finding and treating the remaining cells (myeloma stem cells) that still can exist after typical treatments of transplantation and combination therapies. He discusses how immunotherapies will be used in combination with existing treatments and how with the upcoming ability to personalize treatment based on genetics, we may be able to separate out patients that need intensive treatment and those that can be cured without intensive treatment based on their myeloma's characteristics. He cites the most recent results from tandem transplantation protocols with a review of how therapies can be advanced beyond transplantation.

Jenny: Welcome to “Innovation in Myeloma” a weekly internet series to connect myeloma patients with researchers. I’m Jenny Ahlstrom and I will be hosting this show. I am very pleased to introduce Dr. Guido Tricot, the Director of the Bone Marrow Transplant Program at the Holden Cancer Center at the University of Iowa. Dr. Tricot was educated in Belgium and has served as the Director of Bone Marrow Transplant and Myeloma program for the Huntsman Cancer Institute, the Greenbaum Cancer Center at the University of Maryland and Indiana University. He was also the Director of Clinical Research at the University of Arkansas Myeloma Institute for Research and Therapy. Dr. Tricot has been treating myeloma patients for over 20 years. Because I lived out of the country at the time I was diagnosed, it offered several logistical challenges for myeloma treatment, so I went to multiple facilities over the 3-year period. I had the privilege of getting treated by Dr. Tricot while he was at Huntsman Cancer and what I like the most about him besides overall great care is his very kind attention to detail for his patients. I always knew that I was getting the most attentive care and knew that nothing was missed – every lab result, every myeloma marker, everything was reviewed carefully. He strikes a great balance between attention to detail and very personal and kind interaction. Thank you, Dr. Tricot for joining us.

Dr. Tricot: Thank you very much for your kind introduction

Jenny: Part of your attention to detail means looking at the diagnostic process for myeloma, whether you are newly diagnosed or you are relapsed. So first can you share with us the importance of getting the right diagnostic testing so that we know what we are dealing with as we choose a treatment path? And sometimes we have to make the decision really quickly and immediately if we have active myeloma.

Dr. Tricot: When I treat patients with myeloma I compare this to war and I want to know as much as possible about the enemy as I can. By doing more tests you will know more and more about the enemy and you are less likely to have surprises along the way. If you know a little about your enemy but not enough, the probability that you have surprises along the way will be much, much higher. I like to know as much as possible and I like to take as little risk as possible. I also want to make sure that I do all the tests so that I can see whether patients are really benefitting from the treatment, that I don’t have to wait forever to see whether they live longer or not, that I can see whether it is doing what it is supposed to do and whether they are responding appropriately to treatment and whether I have to adjust my treatment.

Jenny: And what do you look at the most when you are trying to determine that – if they are responding well or not?

Dr. Tricot: There are two important tests in the beginning that I pay a lot of attention to. One has to do with genetics and the other has to do with imaging. And the genetics will give us very quickly an idea of whether patients are likely to do well with the treatment or whether they are high-risk patients. Luckily, with the newer treatments, only 17% of patients are high-risk patients and 83% are low-risk patients and will do very well with our treatments. But even in the high-risk patients, the more intensive treatments will be way superior than less intensive treatments. In terms of wanting to find out how well patients are responding to treatment, the imaging studies become more important. In the beginning we rely heavily on the PET/CT scans to show that patients are responding well to treatments. But once patients are in complete remission, we want to see that all the lesions on the MRI are slowly but surely disappearing. While the PET scan normalizes very quickly after transplantation, the MRI takes a year or sometimes two years to completely normalize. But when the MRI normalizes you know that the patient is in a very solid, complete remission and that most likely the remission will last for a long, long time.

Jenny: I did not know that. That’s great. Now part of my diagnosis included a gene array test which is fairly new. I wanted to talk about this because many patients do not know about this test. I attended a patient seminar and asked this of a group of about 100 patients and about 10% of them had completed this test. Can you tell us what this test is and why it’s important?

Dr. Tricot: We have always known that genetic information about the myeloma cells is important and initially, we did that regular metaphase cytogenetics and then with FISH analysis, but those tests are very rough and imprecise tests that show that there is a lot of damage to the DNA of the cancer cells. In contrast, if you do a gene expression profile, you can look at 35,000 genes with one single test and now you can really focus on the genes, not on large structures that may be normal or abnormal but specific genes that can be down regulated or upregulated and correlate very well with outcome. Based on those gene arrays, we now know who is likely to do well and who is not likely to do well. And especially we know pretty well who is likely to do not so well. We will need to have longer follow-ups since we only started that in 2003 and were the first center to do that, so we don’t even have a 10-year follow-up of those gene arrays, but after about 10-15 years we should be able to identify also patients who are going to do extremely well with treatments and where we can think about decreasing the intensity of the treatment. If we can identify groups that are still in complete remission 10-12 years after having started their treatment with 90% certainty, then we can start to see whether some of the patients actually can do with less treatment and we can start to individualize treatment according to their gene expression profiles.

Jenny: Now I’ve heard about this gene expression test growing in importance for clinical trials so that you can personalize care. Can you comment a little more on how this will be used in determining who gets which kind of treatment?

Dr. Tricot: Well, if you have a high-risk profile, it’s extremely important that you get all your treatments on time. You cannot allow patients to have big gaps in treatments, because the disease will already start to recover again and you cannot allow that. So in high-risk patients it is extremely important to give all treatments on time. In patients that have low-risk disease, the most important thing is to make sure that you don’t kill the patients by giving the treatments too quickly and you can make sure that there is adequate recovery in between the treatments so that they have little risk with the treatments. With high-risk patients, you cannot afford to wait that long. So it gives us an indication of how strictly we need to adhere to the protocol and how quickly we need to give treatments. But our hope is that in another 2-3 years we will be able to identify 90%+ probability of staying in remission for over 10 years and in those patients we can start to see whether we can decrease the intensity of the treatments.

Jenny: So if I am a patient and want to get this test, how do I go about getting it?

Dr. Tricot: There are a few institutions doing that such as in Little Rock and in Iowa and there is also a commercial company who is now trying to get this done. More institutions are trying to work with that company to get that gene array done. We will have to see how reliable their results are compared to what we do because all of those samples have to be sent out and handled after being sent out, but I think overall it will be progress that more and more patients will have access to the gene expression profile. And it will also help us in determining the studies. When you look at study outcome, one variable that you have very little knowledge about is are we really comparing apples to apples. Do we have the same number of high-risk patients as another study or are the better results we see in one study due to the fact that that study had, by accident, many more patients with good prognosis patients than bad prognosis patients. The more you know and the more tests you do, your MRI and your PET scan and your FISH analysis and cytogenetics, the more you likely it is that you can really compare apples to apples and see which treatment is superior.

Jenny: Do you know if insurance will pay for this test if I were to request it as a patient?

Dr. Tricot: When it’s done in Little Rock or by us, the patients have this for free, but with the commercial company that does it, they basically take care of the insurance issues. They will make sure that either they are paid by the insurance company, or if the insurance company for one reason or another will not do it, they will do the test for free.

Jenny: And if I relapse, is it important to get this test again, or if I’ve had it once am I o.k.?

Dr. Tricot: No, it is very important to do this at relapse too. In general the longer it takes for patients to relapse, the more likely it is that the gene array will be similar to what they had initially, while patients who relapse very quickly after treatment usually have a completely different gene expression profile – a much more aggressive gene expression profile.

Jenny: And why is that?

Dr. Tricot: If a patient can stay in remission for 10 years and after 10 years relapses, that means that the treatment was very effective, but not effective in the way that it eradicated everything, but that you basically got down to very, very, very low levels of disease and it takes a long while for those cells to grow up and to cause the disease to relapse again. Usually, if you give a similar treatment as you gave initially, you have the same results as the initial treatment or very close to the same results. Those patients, in general, do well. While if patients relapse very quickly after for example two transplants, we know that those patients had a subset of myeloma cells that was extremely aggressive and in spite of the intensive treatments, grew through the treatments and those patients typically don’t do well with the same type of treatment. They are typically candidates for experimental types of treatments.

Jenny: That leads us into clinical trials. I know that in myeloma, I think it is between 3-5% of patients who are participating in clinical trials, so you have research progressing at this steady pace, but a slower pace than most patients would like. I’ve talked to someone in childhood cancers where they say maybe 85% of patients are participating in clinical trials because parents are taking their children to different research facilities and really pushing forward these trials and because of it, they’ve been able to cure some of these diseases like childhood leukemias or been able to have very good progress in research. Do you feel that more progress could be made a faster pace in myeloma if we increased enrollment in clinical trials?

Dr. Tricot: It would certainly be very beneficial if we can have more patients participate in clinical trials but many patients these days are treated for myeloma by their local oncologist, totally off-trial and they come to us only after they have failed all of the typical treatments and are in much worse condition at that point in time and are no longer candidates for our upfront trials to see whether we can cure this disease. The difference between adult trials and trials in children is usually related to the fact that each of those pediatric centers see a few of those patients a year and they don’t have the population to really do trials themselves. The only way that they can get to some good data is by all working together and by all participating in the trial. In adult trials, we usually have more patients with a certain disease and it’s easier to do trials by ourselves. The problem with multi-institutional trials is that you have to compromise. Not everybody thinks the same way and some people are less aggressive and some people are more aggressive and you will have to compromise to some degree. Sometimes those compromises can be acceptable and sometimes you think this is a compromise that I cannot accept because I don’t think it is beneficial to my patients. We need to make it so you can do trials with institutions that have a similar mindset and have similar goals, otherwise it becomes very difficult. In myeloma, there is this major difference in opinion between different groups where some people think that myeloma is an absolutely incurable disease and therefore it should never be treated aggressively, while other people think, just like we do, that this disease can be cured and therefore it is beneficial for it to be treated as aggressively as possible. The last trial that we did in Arkansas that I participated in, Total Therapy 3 which has a median follow-up of almost 9 years, we saw that at 5 years, patients who had achieved a complete remission that only 11% of those patients had relapsed and 89% of those patients were still in complete remission. That was excellent data. And also in the Total Therapy II arm, where patients were randomized between two transplants with Thalidomide or without Thalidomide, that in the Thalidomide arm, patients who had achieved a complete remission, that 60% of those patients were still in remission at 10 years. So if you can keep 60% of your patients in complete remission after 10 years, it’s hard to imagine that this is not a curable disease and therefore I think we are justified in trying to aim for a cure even if we are willing to take a little more risk up front by giving our more intensive treatments.

Jenny: So if you look on clinicaltrials.gov and see the over 540 open myeloma trials, and there are various “standard” protocols depending on opinion that may not be on a clinical trial, how do you recommend patients weight the costs and benefits in joining a clinical trial. Do we as patients get a standard treatment when we are newly diagnosed or do we wait to join a clinical trial when we relapse or do we search one out when we are newly diagnosed? It’s such a confusing time when you are given this diagnosis. You are just trying to stay alive. What are your thoughts on this and what do you recommend to patients when they have those decisions to make?

Dr. Tricot: In multiple myeloma just like in any form of cancer, you only have one shot at cure and that is in the beginning. Once the disease comes back, you can make people live a few more years, sometimes 4, 5, 10 years, but you cannot cure them. They ultimately will die of their disease. So if you want to have a shot at cure, it behooves you to be as aggressive as possible in the very beginning, not when people have relapsed. If people have relapsed, the chances of cure are basically minimal and you have this very intensive treatments that are going to result in inferior results compared to if you do the same thing up front when the disease is still naïve and the myeloma cells have no idea of what is coming to them. At this point in time, the thing that works the best for us is first trying to de-bulk the tumor – trying to get as many tumor cells killed as possible with tandem transplant and then when that is done, to introduce the newer drugs such as Velcade, Thalidomide, Revlamid to take care of the little bit of remaining disease. That has worked better than trying to start with treatments such as Velcade, Thalidomide or Revlamid up front where you expose those drugs, which are relatively weak to a large amount of tumor cells and will always find some that will escape the drugs and you make them resistant up front. So you first try to give your heavy weapons to get down to as low a level as possible, and then you come in with your somewhat weaker weapons.

Jenny: Can you please share with us your current research and what you are working on?

Dr. Tricot: In terms of clinical trials, we try to go to transplantation as quickly as possible. We only give a single induction or cycle. That cycle is mainly intended to collect as many stem cells as possible so we can do the transplants as safely as possible. If you would not have to collect stem cells, we would immediately go to transplantation because it is the most effective treatment. But after that one cycle after we have collected our stem cells and we have a good amount of stem cells, we start immediately with our first transplant and then with our second transplant. Once patients have gone through the second transplant, then we start with maintenance therapy for two years with the newer drugs and the newer drugs certainly have made the outcome for myeloma patients a lot better, especially if given after transplantation.

Jenny: Are the open trials solely focused around the tandem transplants or adding in the newer drugs or therapies? Can you describe what they are?

Dr. Tricot: In our center we focus mainly on the tandem transplants, except for patients over the age of 65. Most of those patients are covered by Medicare, where we give a single transplant with maintenance therapy and we are trying to see if those patients do better than things described in the literature with non-transplant modalities. As you know there are many people that think anyone over 65 by definition is no longer a candidate for transplantation. But people over 65 these days do a lot better than they did 20 or 30 years ago. Most of those patients are still in excellent condition. A patient who is 70 years old has additional life expectancy of another 18 years, and they want to enjoy as many of the 18 years as they can and be treated aggressively, even if that means more toxicity up front, if they can get more years out of it.

Jenny: I know that if you look at seer.cancer.gov you can see these average life expectancy approaches. Another patient, Gary Petersen, went to multiple facilities – I know he wasn’t able to get it from some facilities, but he compiled data that he posts on his www.myelomasurvival.com web site. I think for patients, it’s helpful to see outcome data. I don’t know if you have any other recommendations about how patients can analyze the data for themselves and make educated decisions about their care when they have to make a decision.

Dr. Tricot: The most important thing that patients need to realize is that it is not a matter of convenience, it is not a matter of "Can I get my treatment close to home or not?" It’s a matter of survival. You need to get a treatment that gives you the highest chance of surviving with good quality of life, as long as possible. Unfortunately, there is nothing more inconvenient than dying way too early because you did not get the optimal treatment. And so I think it’s important that patients go to centers that specialize in this disease, just like a car mechanic who repairs 500 cars a year knows better what to do than a mechanic that repairs 2 or 3 cars a year. Doctors who treat only myeloma and specialize in that will have a better feel for how to best help patients with myeloma. It’s important for patients to find out how many patients with myeloma are seen in that center and the second most important thing is that they find out what the results are of that center. How many of their patients are still alive at 5, 7 and 10 years, not at 1 and 2 years. It’s easy to make a myeloma patient live for a year or 2 years. It is much more difficult to make myeloma patients live for 5, 7 and 10 years. That is really what you need to know.

Jenny: And if a patient just asks, should they be able to provide the data?

Dr. Tricot: If they don’t provide the data, it means that they don’t analyze their data and they basically have no clue what is happening to their patients. Unfortunately, many transplants are done by physicians who transplant multiple, different diseases and as soon as the transplant is done, they are sent back to their doctors and the transplant physicians have no idea what’s happened long-term to their patients. They do well but they actually don’t know. When we see a new patient with myeloma, we follow those patients all the way through. We know exactly how many of our patients are alive at 5, 7 and 10 years.

Jenny: That’s great. Can you share more information about your myeloma practice at the University of Iowa?

Dr. Tricot: I came to the University of Iowa about a year and a half ago and the first year I had about 120 new myeloma patients. This year will probably be around 150. That’s a good number of patients to see. On the one hand you want to make sure that you see enough of them so you can do the appropriate studies, but on the other hand, you need to make sure that all the patients you commit to you can treat optimally - that you don’t go for large numbers at the expense of quality. You need to find a balance between on the one hand being able to see enough patients and on the other hand being able to still deliver the best possible quality of care. That’s what we are trying to do in Iowa. We also have very active research going on that is directed towards myeloma stem cells.

Jenny: Can you share a little bit about that?

Dr. Tricot: We used to think that every cancer cell was the same – and had the same possibility of causing the cancer to come back. Now we know that there are two different sets of myeloma cells. There’s the large majority of the cells are what we call more mature myeloma cells and those cells cannot cause the disease to come back, while there’s a small fraction of cells (usually less than 1% of the cells) that we call myeloma stem cells which have the capacity to have the disease come back if you don’t eradicate them. Most of the treatments, especially the newer treatments such as Velcade, Thalidome, and Revlamid, have good effects on the more mature cells but do not have any effect on the myeloma stem cells. If you cannot eradicate myeloma stem cells, you cannot cure this disease. At this point in time the only treatment that is effective in eradicating the stem cells are the treatments that can cause such a severe bone marrow suppression that you need stem cells to rescue the patients from this severe bone marrow suppression. Those are drugs like high-dose melphalan, high-dose busulfan or high-dose BCNU. If you cannot eradicate the hematopoietic cells with your drugs, you cannot eradicate stem cells in myeloma. In addition to that, we still need to find ways to eradicate myeloma stem cells that survived tandem transplants and that is what we are focusing on. Within the next year we will start a trial focusing on patients who have their disease relapsing and need another transplant to see if we give maintenance therapy with drugs that specifically target those myeloma stem cells where we can lengthen the duration of their remission after the salvage transplants.

Jenny: If the myeloma stem cells are still remaining how do you determine that? What test shows that? Dr. Tricot: That is a very good question and it has taken us about two years to find out what the best test is to measure the quantity of myeloma stem cells and we do that in the peripheral blood. And we have a good test now to tell how many of those stem cells are there and how effectively they are eradicated with the transplants. We have now submitted another grant to the NIH to see whether we can use this test to predict who will do well and who will not do well after transplantation.

Jenny: Great. Can you tell us a little about immunotherapies. It seems to be kind of a hot topic and can you share with us what you know about those?

Dr. Tricot: There are two forms of immunotherapy. One is with monoclonal antibodies and the other one is with infusing cells that can kill specifically the myeloma cells in this case, but it is the same for leukemia. Monoclonal antibodies in myeloma have been difficult to get to. In contrast to non-Hodgkins lymphoma, where we have the CD-20 antibody, which has been extremely effective in non-Hodgkins lymphoma, especially when combined with chemotherapy, we don’t have anything in myeloma yet that is equally effective. But in the last 5 years there have been 5 or 6 monoclonal antibodies developed and now they are all in different stages of phase I or phase II trials and I am pretty confident that within the next few years we will have monoclonal antibodies which will help patients with myeloma. And again they will not be given in a way where they replace transplantation or the newer drugs, but they will be given in a way that they compliment the treatments we give at this point in time so that we see better and more durable responses. The other part is you can educate your T-cells to specifically kill myeloma cells and fortunately in myeloma, the T-cells are of such poor function that it’s very difficult to educate myeloma T-cells and in the last 5 years we have more focus on another type of cell that doesn’t need education that can still kill myeloma cells which we call NK cells or natural killer cells. That work is ongoing and we need to see how effective those treatments are.

Jenny: When you say that immunotherapies may be used with existing transplantation, would they also be used with the existing drugs like the Velcade, Revlamid, etc?

Dr. Tricot: Yes. If we had good monoclonal antibodies, they should make any type of therapy more effective.

Jenny: So it is like adding another tool to the arsenal.

Dr. Tricot: Yes because monoclonal antibodies work differently than the other drugs we use. All the other drugs we use, the cells can find a way to become resistant to those. The monoclonal antibodies, it’s much more difficult. They don’t care how much damage is done to the DNA and whether there are new mutations in the cells or not. They just see whether there is a certain marker on the surface of those cells and if that is present, they will be killed. It works in a different way and therefore should be very synergistic and add to any effective type of treatment if we can find the right monoclonal antibodies.

Jenny: Is that something that is coming immediately, 6 months out, a year or what do you think the development will look like?

Dr. Tricot: It will probably be another two years before those studies will be starting for combination studies. At this point in time the studies that are being done are with monoclonal antibodies only. One of the challenges we have these days is with the different treatments we have in myeloma, the newer treatments are being given to patients later and later and later in their disease when the disease is more and more resistant. There are six or seven ways in which we can treat patients with myeloma and they have to have failed everything before we can give those monoclonal antibodies. Once the cells are extremely resistant, it becomes more difficult to see whether they are really effective. As with everything, when you give it up front, this will be much more effective than if you give it when people have failed seven or eight other types of treatment.

Jenny: Thank you so much for explaining that. So my background is in technology where there are different types of innovation. There is incremental innovation, making something incrementally better, service innovation, distribution channel innovation, and then in technology they talk about “disruptive” innovation, which is something completely new but solves an old problem. I guess in myeloma, you would call disruptive innovation a “cure” or defining a cure or finding a cure. Where would you see this disruptive innovation or a cure coming from in the world of myeloma beyond the patients that you are seeing that have 10 or 20 years worth of remission at this point?

Dr. Tricot: I hope, and that’s why we have our research, that a disruption will come from targeting myeloma stem cells and that if we can deal with those cells effectively, that we will really have a good chance of curing more than half of the patients with myeloma and hopefully more, as close to 100% as possible. But disruptive innovations are usually a total departure from what has been done in the past and is based on a totally new concept and a new idea. Most of the trials going on only are minimal changes from what has been done before and the minimal changes usually don’t result in major changes in outcome. It is something that departs totally from what has been done in the past that has the most likelihood but is also the highest risk, but the most likely of being totally new and innovative. Like introducing stem cell transplantation as was done by Dr. Barlogie in the late 1970’s, it was a total departure from what was done before, where everybody thought myeloma patients should be treated as gently as possible since there was no cure possible and most of the patients were older and if you were going to give something more aggressive they were going to totally fall apart. While the idea of Dr. Barlogie, and subsequently of us, is that if you give intensive treatments and you can get the disease under good control, that patients would feel a lot better, that the fact that the patients were brittle was not due to their underlying age, but was basically due to the underlying disease and if you control the disease, patients will do a lot better and that turned out to be correct. So it was a disruptive type of innovation. I think we now need to take the next step and I hope that lies in the myeloma stem cells – that’s why we are focusing so heavily on it.

Jenny: I agree and I think that disruptive innovation in the medial field is tough. It’s easier in the technology field, but in medicine it is a real challenge because it’s a very risk averse environment in a lot of ways.

Dr. Tricot: Well, it’s a very litigious environment unfortunately and so a lot of hospitals and a lot of academic centers, they try to minimize any type of potential legal risk and they are very careful. If you introduce a new treatment and you are unlucky and the first two patients are not doing well, you have a very high likelihood that your trial will be stopped, that you cannot continue with the trial although if you would have done it, it could have revolutionized the field. You have to remember that if you give new treatment, that it also takes a little time to adjust to the new treatments to know how to best give them and how to give it in a safe way. You usually cannot do that with the first or second patient but after you have treated 20 or 30 patients, you have a much better feel for how to do it safely. But unfortunately, since most people try not to take any risk and to try to protect the institution, it becomes difficult to do disruptive innovations in medicine. But again, the disruptive innovations are the ones that are really moving the field forward, not in marginal increments.

Jenny: I agree. I saw Dr. Robert Kyle and asked how innovations happened in myeloma and he said “mostly serendipity.” That’s a challenge and I think that’s happened a lot in medicine where sometimes they are accidental. Sometimes they are not.

Dr. Tricot: There are some things that have been accidental. The way Thalidomide was discovered in myeloma was largely accidental, but the way that transplantation was introduced in myeloma was not accidental. It was hard thinking and disruptive innovation.

Jenny: It’s more of therapy for the stem cells. How did that originate?

Dr. Tricot: The way we got to that was that we did gene arrays in the very beginning and before the first transplant and before the second transplant and after the second transplant. And before we start any therapy, we had a certain gene array pattern but we didn’t think this pattern was that important because we can get 85% of our patients in complete remission. When a patient goes into complete remission, it means that you have eradicated 99.9% of the myeloma cells. It means the large bulk of the myeloma cells are sensitive to the chemotherapy. But we still see patients relapsing so it still means that we have left behind a more resistant clone and we were thinking, how can you get to those cells and what are the features of those cells and how can we learn from those cells? And we did that by letting nature do its work. We gave the chemotherapy and all of the sensitive cells disappeared and you are left with less sensitive cells and you give your next therapy and you have even less sensitive cells. And ultimately you get to the very resistant cells and then you want to see in many, many different patients what is common is all those very resistant cells. Now when we looked at that, the pattern that we saw was typically described in cancer stem cells and that’s how we got to it.

Jenny: Great. Thank you for explaining that. I would like to open it up to caller questions for a few minutes.

Caller: Thanks Dr. Tricot for the great insights you are sharing. My name is Justin and I’m currently working on a project in pediatrics where we are creating a shared data network across different pediatric institutions for the purpose of generating more insights and having a larger, more complete data set on which to do research. It seems that pediatrics is ahead of the curve in terms of driving towards a robust health learning system because there is more willingness to collaborate. My question is what are the barriers you see in the adult populations to researchers and clinicians to being more willing to share patient data with each other with the purpose of generating new discoveries and I saw recently that the American Cancer Association announced a prototype called CancerlinQ which is now trying to create a shared data pool for cancer research and wonder if that could potentially be a step towards a more collaborative environment around research for cancer patients.

Dr. Tricot: In terms of sharing data for research, I think that is finally starting to happen. If you can find gene expression profiles of thousands of patients with myeloma that you can analyze and try to find out certain things. Unfortunately when it comes to clinical trials where you are treating patients in a similar way, that has been much more difficult and we still are behind where Europe is. In Europe, you see many more large, cooperative trials where big institutions collaborate to do the same thing and therefore can finish a trial in a short period of time where it takes us much longer at a single institution or two institutions to have the same number of patients. Again you need to make sure you work together with people who have the same mindset and have the same approach to treatment, rather than having all types of people collaborating with you who have different mindsets and where you basically have to compromise too much where you think this is not really going to help my patients, but again there should be ways to do a much better job than we are doing at this point in time by similarly minded people and physicians working together to the benefit of the patients.

Caller: This is Paul and I’m a caregiver. One of the most impactful things in the interview is the outcome of your trial at the University of Arkansas. I think if I wrote it down correctly, you had more than 60% of patients living after 10 years. Did I hear that correctly?

Dr. Tricot: Yes, 60% were still in complete remission after 10 years and these days we achieve a complete remission in about 85% of our patients.

Caller: If that’s the case, why isn’t this data out there more widely published? This seems like one of the best kept secrets in multiple myeloma.

Dr. Tricot: I fully agree with you. Ninety percent of the patients with myeloma are not treated in an adequate way in my opinion, but we can only put the data out there and people are trying to do the same thing which was done in Arkansas and what we are doing now but unfortunately they are doing it in such a way that it is not completely the same. If you want to have similar results you need to do it entirely the same way that it was done before and then you can see if it is true or not true. It’s just like when we did the tandem transplants and people said “Well, that’s not any better than a single transplant,” until this was repeated by two big groups in Europe that showed that two transplants was indeed better than a single transplant.

Caller: Where can we go to see this data published and have access to this data?

Dr. Tricot: The most recent update on the Arkansas data was published in the Leukemia journal last year and you should be able to find it there. If you have difficulties finding it, send an email to Jenny (jenny@crowdcare.org) and I will make sure that you get a copy of that paper. (see this link for the article referenced)

Caller: Thank you so much.

Jenny: We have another caller.

Caller: My name is Abby. I have an interest in the medical space as a medical student and I’ve noticed that the research structure in terms of promotions is a little off in incentives to researchers because researchers aren’t truly incentivized to go after truly disruptive research. The culture around failure in scientific research is not the same as is the case in other contexts, so there is this stigma around failure and researchers are afraid of going after things that are disruptive. I applaud you on taking on disruptive work. Along those lines, besides stem cell transplants, what are the truly breakthrough therapies that are out there today for treating multiple myeloma.

Dr. Tricot: Well, the non-transplant treatments have improved outcome, but you have to remember that even with the best non-transplant treatments, that only 40% of the patients are still alive at 5 years. If we compare that to what we saw with Total Therapy III, where the median survival of patients is going to be somewhere around 12 years, based on the way the curve is looking at this point in time, and was 10 years in the Thalidomide arm in Total Therapy II, the outcomes with non-transplant regimens are still clearly inferior. The reason that this is inferior in our opinion is because the non-transplant regiment cannot kill the myeloma stem cells. The only way that you can deal with myeloma stem cells is by doing transplantation at this point in time, but that doesn’t mean that in the future that if we find ways to deal with the myeloma stem cells and we can first get the patients in complete remission with non-transplant modalities, and then introduce the myeloma stem cell therapy, that we will be able to cure patients without transplantation. At this point in time, that doesn’t exist.

Jenny: Thank you so much. Dr. Tricot, we are so grateful that you were able to join us today.

Dr. Tricot: You are welcome.

Jenny: We appreciate your time and your responses. Dr. Tricot is included in our doctor directory on the www.mpatient.org web site. If you would like to contact him directly, you can send him an email via that doctor directory listing and it will be sent to his department and he can respond to you in that way.