Full Show: Dr. Martin Kaiser on Myeloma Treatment in the UK and the Study of Myeloma Genomics
Thanks to our episode sponsor, SparkCures Martin Kaiser, MD Institute of Cancer Research Interview Date: February 5, 2018 Summary Martin Kaiser, MD of the Institute of Cancer Research in the United Kingdom joins Myeloma Crowd Radio at ASH 2017 to discuss myeloma care in the United Kingdom and how the aggregation of myeloma genomic data from over 4,000 myeloma patients has helped advance myeloma research. He shares a new study for high-risk newly diagnosed patients in the UK at over 20 hospitals and discusses two genomic tests that are being run on these patients to better understand disease progression when it happens early for these patients who are more likely to relapse early. Dr. Kaiser on Myeloma Crowd RadioFull Transcript Jenny: Welcome to Myeloma Crowd Radio, a show that connects patients with myeloma researchers. Im your host Jenny Ahlstrom. Wed like to thank our episode sponsor, SparkCures for their support of this Myeloma Crowd Radio program. SparkCures is a myeloma clinical trial finder that you can find on the Myeloma Crowd website and is a wonderful way to easily find clinical trials. We have with us Dr. Martin Kaiser of the UK and we are here at ASH 2017 together. So Dr. Kaiser welcome and thank you for joining us. Before we get going, let me introduce you. Dr Kaiser is a Clinician Scientist at The Institute of Cancer Research and Honorary Consultant Haematologist at The Royal Marsden Hospital, London, UK. Dr Kaiser attended medical school and obtained an MD degree in myeloma research at the University of Aachen (RWTH), Germany and completed his specialist training at Charité University Hospital in Berlin, Germany. In 2011, he joined The Institute of Cancer Research (ICR) and since 2014 Dr Kaiser is heading the Myeloma Group at the ICR. His research focuses on integrated molecular profiling for biomarker and target identification for stratified medicine in multiple myeloma. So he works on specific areas of activity like genomic and epigenomic molecular profiling of high risk myeloma, and epigenetically driven disease. Through collaborations with the ICRs Division of Cancer Therapeutics and external partners, the group also explores novel and innovative tool compounds and candidate drugs for pre-clinical and clinical drug development in myeloma. Dr Kaiser heads trial-specific myeloma biobanking for multi-centric UK Myeloma Research Alliance (UKMRA) trials and for studies in the Myeloma UK Clinical Trials Network. He is Chief Investigator of academically-led trials with a particular focus on genetic stratification and biomarker discovery. In collaboration with Dr Messiou (Royal Marsden Hospital, Radiology), Dr Kaiser is investigating innovative imaging methods for improved patient care, in particular diffusion-weighted whole body MRI. Dr Kaiser is member of the UK NCRI CSG Myeloma sub-group, elected member of the Executive Board of the UK Myeloma Forum (UKMF) and Lead for the Genomics England GeCIP Haematology sub-group for myeloma. So Dr. Kaiser we are happy to have you and look forward to our talk today. A lot of excellent research has come out of the UK, and theres a strong patient advocacy group as well in the UK. Could you give us perspective of treatment of myeloma in the UK? Dr. Kaiser: Yes, of course, I see it as a big advantage having seen how different systems work and how they might impact on patient care. I think in some sense, the way how I trained and how I work in the UK, of course, there are a lot of similarities because both healthcare systems which do define the drugs that are available for a broad population effectively. I think what makes it a bit more special in the UK is that there is an attempt to have a patient pathway in terms of what the different lines of therapy are that can be given. And that has both up and downsides. Jenny: Okay. So youre saying there are differences in treatment options. Dr. Kaiser: There are differences in treatment options, and I think theyre along the patient pathway. I think there is a clear availability of very effective treatments at each stage of the disease, but it is not necessarily a free pick that you can choose whatever you want. But there has been, of course, data produced as part of clinical trials and that leads to an approval that is really for a certain indication and a certain point in the disease where this type of regimen can be given. Assuming that, of course, we are doing personalized medicine, we are adjusting the doses, we are looking at what the patient wants, were taking all aspects into account, the personalized medicine that doctors have done ever since effectively which is a different type of personalized medicine than the one that is now were entering into with molecular stratified treatment. All of these things are still going on, but nevertheless it gives more of a clear sequence of what can be given at which time point. I think there are certain elements of that that sometimes make you want to be probably a little bit freer in what available and see what you can pick. But on the other hand, once the drug is approved as well, a patient can really access it without any barriers. And I think that is a big aspect. Its just something that's so deeply built in to the UKs healthcare system that once a drug has been through the approval process, it is truly available. There are no ifs ands or buts. There are no other levels and anymore of intricacy that sometimes can mean a patient can have a drug, for example, as an inpatient but not so well as an out-patient or the other way around. And I think thats what were often facing at the healthcare systems that there are slight differences. I think what is good in the UK as well is that it is really considered a joint resource. There is a constant process going on to look at how to best use the resource. So oral agents are always favored over very difficult to administer drugs, for example. Its not saying that these drugs, they're very efficacious. They're still given, but I think it is very much in the patient favor as well that its looked at things that are easy to administer, easy to take, easy to give the patient effectively a lifestyle as well that is as compatible with all the challenges that were all facing in our lives all the time as possible. Whereas, sometimes in other systems, there might be an incentive to actually rather favor intravenously given therapies despite them probably being equally as efficient as an oral drug, for example. So these can be advantages as well. I think Im very lucky to have experienced both types of systems with their slight differences. But Im very glad that we could give patients the care and the access to drugs most of the time, although we always want to have more available and full on with the new developments, of course. Jenny: I have a question about clinical trials. I know European clinical trials are different from US clinical trials. In France for example or other countries, patients might go into trials that the experts constructed that are really large scale. Is that the case in the UK? They have very high participation rates in the trials but it seems theres less variety in trials. In the US theres more variety but more difficulty accruing so there are positives and negatives on both sides. Dr. Kaiser: I think there are different aspects. I think some of it has to do with that there is a public healthcare system that has been designed from the beginning as having an inherent research aspect embedded in it. So I think this is probably a right assumptions by many patients that they do understand that public healthcare systems can only work and evolve and actually produce novelty if they participate in trials as well. And in some circumstances, it might give them as well an advantage in having access to a drug that is not available on the public healthcare system, but most of these trials are randomized. So at the end of day, we can never guarantee that the patient will get access to the newer drugs. In some sense, I think it is deeply imbedded as well that there is a clear desire or a clear willingness to really contribute to the progress. Nevertheless, I think there is an aspect, of course, that if you have a healthcare system like in the US where drugs are probably approved faster or the approval often comes first through the FDA and is then free to prescribe by any physician, there is, of course, more of a choice and that can just mean that people might not want to consider going into a trial where they actually cannot choose themselves but it will be a random assignment to the one or the other drug. Jenny: Lets go back because you mentioned the oral therapies and those options seem to be growing in myeloma. What is your opinion about the move from doublets to triplets and new options patients may want to consider . Dr. Kaiser: So I think it is great that increasingly more oral agents are available, and luckily really most of the oral agents that are around, they are really well tolerated, which is one has to say in comparison to other tumor types, luckily, for many of the other drugs that we use, true. But I think there's particularly still a really good feature of many of the drugs. There's so much experience now with them or they actually have such a biological background that they can be taken and tolerated for the intensive periods of treatment but also for maintenance type of therapy. Thats very important in myeloma. The most important use I think of oral agents is really in the maintenance setting. That doesnt mean that I dont think that they should be taken and there are induction treatment settings as well. But I think that is really where they make such a huge difference because it can be -- many years now luckily that patients stay in remission on a maintenance therapy, and not having to come to the hospital that often is making a huge difference. So we have, at the moment, Revlimid, for example, approved as a third line of treatment drug in the UK which is as such great in that we can use it for as long as we want in that setting. And we do have a lot of patients that are having ongoing benefit and continuous benefit from taking this maintenance drug. Were hoping that this will probably move into early lines of treatment. And here at this meeting, Graham Jackson has just shown the results from the large Myeloma XI trial that was run in the UK. That provided really elemental evidence for Revlamid maintenance therapy in particular after transplant. It was a large trial. As we spoke about earlier, many patients in the UK were really very happy and willing to go into this trial. And I have treated a lot of them myself as well and had seen them benefit from it. So Im not surprised especially in the transplant setting, there is now a demonstrated overall survival benefit as well, so really a long-term effect of patients going on to this maintenance treatment. The first trial on its own as one single trial in a predefined setting really found this overall survival advantage. There has been a recent meta-analysis that is completely in harmony with this finding now. So I think that is a very important finding, a very important case for this type of treatment after autologous transplant. We do see that other agents of being tested in that space at the moment as well. There are the oral proteasome inhibitors, for example, that are, particularly ixazomib, which has been tested and Im very much looking forward to the outcomes of the Phase III trial. Again, another trial where a lot of patients from the UK participated as well. I think that is really a very important space for the oral agents. In the different phases of induction treatment, we are trying to use triplets as well. This is where particularly in the healthcare system, it is not globally possible to use two novel agents together. We do have an induction therapy with Velcade, thalidomide, and dexamethasone available and thats very effective actually. But when it comes to combinations, for example, like Revlimid and ixazomib, at the moment at least, that is not possible. This might become available on the healthcare system which would be great as well. I think its another very effective regimen. But I think really a very big impact is the maintenance setting. Jenny: Oh, I agree and Im hearing that everywhere. Lets talk about the clinical trials you have open and how patients can find UK clinical trials. Dr. Kaiser: So clinical trials in the UK are often registered on official portals that you have just mentioned them. There is also a very active patient information organization, Myeloma UK, who does keep a register of sites that are participating in clinical trials, and thats another point of contact. I think we do have a very closely-knit community in hematology specialists in myeloma as well. So clearly, their treating physician will be very happy to keep an open eye for any trials that are not available at the local center are actually available relatively close to where the patient lives. The treating physician will be very happy to advise the patient on where a trial is potentially open close to where they live because the distances are not so long normally and are not so far in the UK. In terms of trials, it is really a unique setting that the healthcare systems does have an inherent research aspect, so there are a lot of academic trials going on. There is a long tradition of having trials for the newly diagnosed patients. Were now at the moment in the phase where the large Myeloma XI trial has finished recruitment. A certain while ago, were now seeing the amazing outputs of that trial and the amazing results of the trial which will hopefully lead to the really knock on effects in terms of what is available and what is possible and in terms of treatment. We have then a number of trials that really tests concept and that are trying to push boundaries. These are run sometimes in the newly diagnosed population but often as well in the relapsed/refractory population. And many of them are run again with Myeloma UK which has been a very early on understanding organization to actually contribute to set up clinical trials. So it interacted very early on with the NHS embedded research infrastructure and made a case for myeloma patients in particular to actually access certain aspects of their infrastructure. So it is easier to set up a trial and to find the collaborators that are always necessary, for example, in pharma to get really novel drugs, novel combinations to patients in the UK. Off the trials that are currently running, we have just started the trials for high-risk patients. This is really a first and I think in its scale not only a first in the UK, I think it is internationally quite a unique design and quite a novel setup. So we have designed a fairly big study because we wanted to really make this impactful and have as many patients benefit from it as possible. So were going to screen 600 newly diagnosed patients. Thats big. And were really lucky that we could draw so much experience from our genetics works that we did before on the large Myeloma XI trial which in total included 4,000 patients, more than 4,000 patients. So that we had really solid data on how really to best identify patients with current treatments, unfortunately, are not doing so well and that could benefit hugely from having more innovative approaches and really getting access earlier to the novel drugs that are clearly showing very much benefit in the relapsed/refractory setting. So there is little doubt that they will have a big impact in the newly diagnosed setting as well. So the design is that these patients do give their bone marrow which is sent to our central laboratory at the Institute of Cancer Research to be then immediately worked on, molecularly profiled. We do tests for genetic operations. Were using a molecular test that is consisting of a method that is called MLPA. It is a difficult abbreviation actually, but the concept is that we can test the copy number status of different regions. So whether there is actually more genetic material or less than there should be in the cancer cells, very rapidly for many samples in parallel. In the old days or until recently, in many centers still, the standard method is FISH which is a very good method. I think there is no reason to be critical of the result as such. But it a just a method that has a certain maximum number of samples that a human can just process. There is no straightforward automatized process of analyzing the data. Thats why we have actually analyzed pretty early on this MLPA method because we had a set of patients from earlier clinical trials. Again, this is really at the core of everything that we do that had FISH data, so we could easily compare whether this new method is actually exactly giving the same results. And it did. So we published that as well. This has fed back as our experience now into running this trial. Also, we had another method which is effectively a PCR which looks at whether genes that are involved in translocations are highly expressed. So whether these genes are having multiple copies of the genomic region are red out and if that is the case, we know that from early work, for example, from Bergsagel's group that shows that there is a genomic change which has happened in that region effectively, so we can call translocations with that. Thats one side. So we actually for the t(4;14) translocation, t(4;16) translocation, deletion of 17p and gain of 1q. We have found before that that these lesions, unfortunately all of them do confer risk of the disease comes back earlier. But, in particular, if two of them have met at the same time or found of the same time, the risk is even higher. And if you have a treatment that could potentially mean more effort for the patient to come more often, you want to make sure that youre treating the right patient. Youre not treating someone who might have had effectively a very similar disease history from there onwards, but you want to make sure that you really serve the patients most that have the biggest need. Another method that were using is gene expression profiling, and Im sure many of the listeners will be very familiar with that. This is something that has been probably more broadly applied in the US for some while. There are now standardized tests in Europe as well that have been developed by the Dutch group originally. That is the Skyline assay and that is the standardized assay, so we can implement it. We have decided to implement that into this trial as well. And that was again coming from data that we analyzed in the large Myeloma XI trial where we actually looked at genetic risk and gene expression risk. And we were curious, are these actually the same patients if you apply the one method or the other? Because there were very few or actually virtually no data of people that had really looked for both of them. So we looked for patients that had these two operations genetically which we also internally at least termed double hit. We tested the same patients whether they had a gene expression high risk marker. We found that some of them were identified by both methods. But there was a subset of patients that was only identified by the gene expression high risk marker and another set of patients that was only identified by the genetic double hit high risk feature. We decided actually that it would be absolutely adequate to include all of them because we do see that they unfortunately all have a shorter duration of remission with current treatments. And if one applied only one or the other method, one would probably miss patients that are really in need. We were on the one end side, of course, puzzled by this finding and we still are working very hard on understanding why two different methods identify different patients. But the pure fact that they all are in need of better treatments made us, of course, very motivated as well that we can use both methods together to confer the biggest hopeful benefit for the patients by enrolling them into this trial. Were testing this. Were feeding the result whether this was found back to the patient. And if it has been found, we are offering them participation in the trial where we use not only a triplet but actually, a combination in the beginning at least of five drugs. Jenny: Oh, wow. Dr. Kaiser: So we use a combination of cyclophosphamide, Revlimid, Velcade, daratumumab, and dexamethasone. But we do acknowledge that that is, of course, a relatively intensive regimen. What we want to make sure is that we really offer the patient the best treatment in the early days of the disease. What we want to avoid is that any resistance mechanisms that are happening earlier on. We want to give the patient the chance that the disease is responding as quickly and as best as possible. We do, however, very clearly think that the personalized medicine that doctors have always done is a very important element. So the trial is not strict in the sense that the patient have to carry on at the same dose or at the same schedule. But we built in that the physicians watch very closely how the patients are tolerating this treatment and are reducing drugs early on because what we want to avoid is that the patients have to stop treatment. Effectively, we offer everything but its more like an offer and the physician has to be in the dialogue with the patient, observing the patient, decide how to adjust treatment so that its best tolerated and at the same time offers the most benefit, actually. So these patients then undergo an autologous transplant as well. And after that the drug doses and certain drugs are just tapered off because we do want to keep some or a lot of pressure on this high-risk disease clone in the bone marrow and really push it down to lowest levels. In this trial, we are measuring central MRD, which is another brilliant feature off the UK research group, is that we have a very collaborative structure. So we have the genetics laboratory where Im doing the work and my team is doing the work on the genetic profiling, but were working very closely with a lab in Leeds and that is a lab by Roger Owen and Ruth de Tute, who is the scientist in his lab. Hes going to present data this year at ASH as well, again from the Myeloma XI Trial. But these guys can measure MRD really perfectly. They have the experience of thousands of samples having measured as parts of trials. So measuring this in the high-risk population as well will allow us in this trial, for example, to have earlier readouts. We can take that measurement at certain key time points to see whether patients respond better than patients that we have profiled before from the trials that we have worked on in the past. So we have an immediate comparison actually to patients that have received also very effective treatments but down to the disease biology probably were not benefiting as much as other groups. We can immediately read out whether this other treatment is actually benefiting them more and that will feed into further developments of future trials, for example. Jenny: We are hearing more and more about MRD testing as a potential new endpoint for clinical trials. The UK sounds like you have the advantage of genetic testing, MRD testing, research, patient advocacy and thats just fantastic . Dr. Kaiser: We're very glad. Im very happy. Each day, we're actually able to work together with so many great people in this collaborative and, of course, for the patients that want to take part in this research as well. And I think with this trial, we hopefully have designed something that really brings back a lot of the innovation and the insights that we have won through, of course, previous patients' commitment to giving, for example, bone marrow material but actually really benefitting the next generation because we are applying a lot of the methods that we have developed back on to the patients or for the patients that are enrolled and taking part in this trial now. Jenny: Thats great. What a wonderful collaboration. How many hospitals are in the network? Dr. Kaiser: Yeah. Its been a lot of work. It's always difficult to set up trials. One goes to endless meetings and sometimes comes out and thinks, well, maybe this is stuck now and maybe were not getting anywhere, but it just pays out in the end. It really pays out. The moment that you get something off the ground. So for this trial, there will be at least around 20 hospitals but were looking to extend this trial because, of course, its understandable patients are very interested in this. We want to really give everyone a chance to be considered for this trial. It is a lot of hospitals. We have started with the biggest hospitals, and there really is a very large catchment area if you count them together already. For a large trial that ran over many years like Myeloma XI, the number was even higher. So in total 100 hospitals took part in this trial which meant that really virtually every patient had a chance to take part in the trial like Myeloma XI. And thats the only way how in the end of the day you can really get such a huge trial together that enrolls over 4,000 patients. I think another aspect that was very important about Myeloma XI is that it is a trial that is really for all age groups. There is particularly a group of patients that are close to 80 or over 80 that in reality are a large group of patients with myeloma, but in the normal trials they are not represented. And I think it has to do with lots of factors as to how easy the treatment is, whether its oral, whether its not oral. Myeloma XI had the clear advantage as well. It's a full oral regimen. It was rolled in really every hospital around the country. So it has a very large proportion of these patients as well. I think this is something where a lot of insights will be won. There are already data shown here at ASH that help us understand better the needs and the specific challenges that these patients are facing, whether we can identify markers in the blood, relatively simple markers, for example, that could tell us, look, this patient might be running into trouble just because generally they are not as fit as someone else, for example. And I think we will hopefully be able to derive certain models of care for this type of high-risk patient as well because thats another type of high risk. Jenny: Right. If people have a pre-existing condition that prevents them from getting on a drug thats a high-risk feature in itself. Being as fit as possible to be able to receive some of these treatments is really key. Dr. Kaiser: Oh, yes, thats very important. I have to say its a conversation where I really constantly try to motivate patient as well. I think its a very important aspect. Its very important to make clear that it doesnt take much. It is often about just being out or, in some way, active mild activity. Its doing it regularly. Even if its a long walk regularly, its fine. Keeping semi on your diet, not just to have one type of food but actually mixed, have fruits and vegetables in there. I think its a question that naturally comes up all the time. It is often a question that comes up. The first conversation that I have with a patient about when the disease is diagnosed is what should they do food-wise. I think its very important to understand that it is not a disease that is caused by any wrong behavior, that its not anything where an environmental factor plays a big role. We know that from large studies. But it is, of course, something where, as you rightly say, keeping yourself fit and healthy just generally has so many good features in terms of tolerating drugs better, tolerating your treatment better, knowing yourself better as well, understanding when are you really unwell, when should you go to a hospital to actually be looked after, and when is it maybe just your bad day. Jenny: Yes, not myeloma related or could you go to a transplant even if youre older? Dr. Kaiser: Exactly. We have learned a lot of lessons that absolute age is not really the barrier for a transplant. We do transplant actually quite a number of patients that are above the age of 70. If they are fit, if they want that, we have a very open and frank discussion with patients. Absolutely, there are more and more people around that are very active and fit. Being old is actually probably more a feature of whether you depend a lot on someone elses help. Jenny: I agree. Those frailty scores segment people into fit, unfit and frail categories. So if youre high risk you need to be as fit as you possibly can be. Dr. Kaiser: Absolutely. Thats absolutely true. One has to say, of course, the background of the disease or how its actually working, which we call the molecular feature of the disease, but that in some sense always shines through. It is a feature still that mandates us to be more on the case and to really give the right treatments for the patients so that we can control the disease when there is a risk that it could come back earlier. Jenny: Its an exciting clinical trial. Are there others youd like to talk about? I heard about a CART trial in the UK but I dont know where. Dr. Kaiser: There are academic centers that have developed CAR T cell trials. For example, at University College, there is a CAR T cell trial of a construct that was developed there. But, of course, we are getting as well now, after the initial development was done in the US, we are getting now trial programs as well from the CAR T cells that some of them have already received breakthrough approval by the FDA, for example. I think thats going to be a big benefit for our patients, of course, as well and an important option. I think its an option that we can offer because transplant and transplant centers have so much experience in the UK and doing quite complicated procedures with a lot of patients already. I think its a great country as well from a development standpoint or from clinical trials that we can hopefully offer CAR T cells very soon if they mature further in their development pathway to a lot of patients. Jenny: How do you see immunotherapies in general progressing? Like the BITE antibodies, the antibody conjugates, the monoclonal antibodies and vaccines. How do you see these rolling out in the United Kingdom? Dr. Kaiser: Were starting already. I think we have also been huge contributors as a whole country to the acceptance of daratumumab, for example, development programs as well as the elotuzumab program before. And there are lots of UK patients we've actually treated as part of these trials and have contributed a lot to the outcomes of these trials, all of which are very exciting. I have to say, this is a real amazing development. Its absolutely great that the immunotherapies are coming along. I think the important aspect that they carry with them, at least some drugs that we know now already after Phase III trials, their feature is that they have a very good safety profile and a very good side effect profile that makes them pretty tolerable. I think that opens just a spectrum as how they can be used both in patients that may not tolerate that well because of frailty, for example, certain other drugs but also in terms of the possibilities of combining them with lots of other drugs without adding yet another level of significant toxicity, for example. I think this just gives so many more options. In terms of the new developments that are coming on of the drugs that dont have approval yet that are going through the early stages of development, Im very sure that the UK again will be a very keen participant as whole, as a community in these trials and trials. And I think there is an understanding as well in terms of the regulatory authorities in the UK that these drugs are fundamentally different. Theyre undergoing review at the moment, some of them at least, and we hope seeing them being really being available in the near future. So its impossible to predict. There are many factors that are playing into that, but I think the basic understanding is there. So were pretty hopeful. Jenny: Well, Im grateful that youre participating in all these trials and making data come out so decisions can be made. My last question is, what are the most exciting things youre seeing here at ASH? Dr. Kaiser: I think some of the immunotherapy approaches are really very exciting. The ones like antibodies, like CAR T cells. What Im looking for now here particularly is the really impressive efficacy. Particularly, if its combined with a good tolerability profile, I think that will just make it so much easy to find combinations that we can use together in the future, that were not hitting a ceiling of adding yet another drug that all cause the same side effects and make patients' experience effectively not as good as it could be effectively. Because it is a disease that I think does need these strategies of some form of continuous treatment, with that we have managed to really transform outcomes for patient from unfortunately really short times of remission to patients staying in remission sometimes for ten years longer. So thats the real goal. We do want to transform more the outcomes for our patients that have diseases that tend to be coming back earlier. Were working very hard on that. I think we have made good progress on that side as well. The better understanding of the molecular makeup of myeloma and how it really works is very clearly very deep and close to my heart. So there were a lot of exciting talks about that here at ASH as well which would take another session to really go into depth about that. I think we have seen a lot of technological breakthrough on how we can analyze the genomes, the epigenomes of the myeloma cell. Were working very hard on that. Its very exciting to see other groups are making progress on that front as well. I think that that will be a big area of collaboration in the near future that we can all put all the pieces of the puzzle together to really understand how this disease works to get to the next level of therapeutics that are hopefully as effective and more as the ones that we have already. Jenny: Ive seen a lot about driver or resistance mutations. Maybe these are all pieces to the puzzle. If you overcame resistance, you could give someone ten or more years of life. Dr. Kaiser: Absolutely. I think there is a lot of more effort going on now to really understand how the disease evolves, for example, if it relapses. Luckily, again, through the clinical trials that we have run, we have a lot of patients who gave bone marrow at different stage of the disease. So this is where we are really focusing on at the moment to effectively look at how the tumor changed over time, not only in a handful of patients as it has been done very impressively in the past, for example, by Jonathan Keats's work, but we want to really look at it at a scale of really several hundreds of patients now. And we are in that position to understand more networks. In the end of the day, we have I think more insight that the myeloma cell is not simply built. There isnt just one engine in the whole process, but it has a whole network of different drivers. And understanding how they work together or actually whether there are subgroups in which one whole network is much more active than another one and then actually going with the right drug for that subgroup is going to be the ongoing challenge for the coming years. I think its not as simple as that you will have one golden bullet for something, but we do see now these networks emerging. We do see more that the pieces of the puzzle are fitting together into certain categories, and thats really what we're working very hard on. Jenny: Well, we appreciate your work because once you start defining those, then you can start treating those categories differently. Which brings us back full circle to personalized medicine. Well thank you for all you do for multiple myeloma patients around the world and for joining us on Myeloma Crowd Radio. Dr. Kaiser: Thank you very much for having me. Thank you. Jenny: Thanks for listening to Myeloma Crowd Radio and we hope you join us next time to learn about myeloma research and what it means for you.