Full Show: Important Steps for Dealing with High Risk Multiple Myeloma with Dr. Guido Tricot, MD, PhD, University of Iowa

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Thanks to our episode sponsor Takeda Oncology

Dr. Guido Tricot, MD, PhD
University of Iowa
Interview Date: December 5, 2015

Summary

Dr. Tricot joins Myeloma Crowd Radio from the ASH 2015 conference in Orlando to talk about high risk myeloma. While standard treatments have become much more effective, 15-20% of patients have high risk disease and are not gaining longer life, even with the newer combinations. He notes the difference between more mature myeloma cells, which can’t propogate the disease vs. the myeloma stem cells, but notes that if there is a large tumor burden, the sheer amount can create disease increase. Because the quanitity of cells can cause growth, he suggests that patients move to immediate transplant so they are hit with aggressive treatment when they are still naive to the drugs. One of the most important things patients can do with high risk disease is to make sure that the treatments are given on time with short induction periods. Dr. Tricot shares experience from the Total Therapy studies that patients with 17p deletion benefit with proteasome inhibitors like bortezomib and notes that they should also be used as maintenance therapy where iMiDs may actually be detrimental as maintenance. He has hope for checkpoint inhibitors and is looking forward to incorporating the new monoclonal antibodies in addition to standard treatments. He clarifies the definition of high-risk in patients with del13. He is focusing on new treatments for the MAF translocations using a Notch 2 inhibitor and is working on identifying a marker using flow cytometry that identifies response to treatment. Once tested, it would identify patients who have responded and or not responded and would help determine the course of treatment.

Full Transcript

Jenny: Welcome to today’s episode of Myeloma Crowd Radio, a show that connects patients with myeloma researchers. I’m your host, Jenny Ahlstrom. We’d like to thank Takeda Oncology for sponsoring this episode of Myeloma Crowd Radio and for all they do for multiple myeloma patients.

Today, we’re joining you from ASH, the American Society of Hematology Conference in Orlando, Florida. This is a chance for hematologists and many oncologists to learn more about the latest advances in blood cancers. Many myeloma specialists are here in attendance at the conference including Dr. Guido Tricot.

Dr. Tricot, we’re so grateful you’re taking some time out from this incredibly busy conference to talk with us about high-risk myeloma. Let me give you an introduction before we get started.

Dr. Guido Tricot is Director of Adult Stem Cell Transplant and Multiple Myeloma Program and Professor of the Department of Internal Medicine at the University of Iowa. He’s also a Gary D. Arthur Professor of Adult Bone Marrow Transplantation.

Dr. Tricot is from Belgium where he obtained his medical degrees at the University of Leuven. He performed his post-graduate training at MD Anderson, at the Royal Marsden Hospital in the UK, Roswell Park and Memorial Sloan Kettering Cancer Center. He has been Director of the Bone Marrow and Transplant Program at several facilities over the course of his career including UAMS, the Marlene and Stewart Greenebaum Cancer Center, University of Utah and now the University of Iowa. He’s also served as Director of Clinical Research at UAMS and Director of the Myeloma Program at Huntsman Cancer Center and University of Iowa.

Dr. Tricot reviews publications including the American Journal of Hematology, Blood, Bone Marrow Transplantation, the British Journal of Hematology, Cancer Cell, the Journal of Clinical Oncology, the New England Journal of Medicine and many more manuscripts. He’s also on the editorial board of Bone Marrow Research Leukemia, the Journal of Blood and Lymph and the Journal of Cancer Therapy.

So Dr. Tricot, welcome. I’m excited to have you at ASH and talk to you a little bit about high risk multiple myeloma. We kind of have a broad way of talking about high risk myeloma. But I’ve heard several times here at the conference that high risk disease needs more attention. So do you want to first talk about who’s addressing high risk or who’s not addressing high risk?

Dr. Tricot: The first point I would like to make is the fact that we have made a tremendous progress in the large majority of myeloma patients who have standard risk or intermediate risk myeloma. Those patients have seen median survivals increase from about two and a half years, median survival around 1990 to more than 10 years with the most intensive treatments at this time. Unfortunately, there’s about 15% to 20% of the patients that have high risk myeloma defined best by gene expression profiling and those patients have not done so well with the more intensive treatments. We need to have different approaches for those patients. We should try to make those patients do as well as the standard and intermediate risk patients.

Jenny: And they have more aggressive disease so that’s a bigger challenge?

Dr. Tricot: Yes. Their disease gets into remission almost equally well and equally frequently as the standard risk patients but their duration of remission is clearly a lot shorter.

Jenny: What are the issues that you feel are facing the treatment of high risk disease right now? Why is it so difficult to treat?

Dr. Tricot: In my opinion, in standard risk myeloma, most of the cells are very sensitive to chemotherapy and most of the cells are more differentiated and easier to target with the treatments we have available. In high risk disease, those patients have more features of myeloma stem cells which are much more drug resistant, much more easy to require additional mutations and much more easy to relapse quickly.

Jenny: I’ve heard doctors say that an average patient might have five different kinds of myeloma at one time. So you’re saying the complexity is in having the five different kinds or the multiple kinds or the complexity is in maybe one of those five kinds that might be really just complex if you want to elaborate.

Dr. Tricot: So as you know, myeloma consists of early cells which we call myeloma stem cells or myeloma initiating cells, and those are basically the only cells that can propagate the disease. If you take those cells out and you implant them in mice, they can cause the human myeloma disease in the mice. The large majority of these cells are more differentiated myeloma cells which cannot propagate the disease and if you inject those in the mice, you will not see the disease. But there is one caveat that it is possible for those more mature cells to dedifferentiate to stem cells under the right conditions. So if you inject enough of those cells, instead of a few thousand millions and millions, you will see that those cells actually can give rise to myeloma in the mice. And that’s because one of those cells has gone back from a more differentiated cell to a less differentiated cancer stem cell.

Jenny: So a quantity problem can cause the issue or I guess you could call it a quality or characteristic problem can cause the issue.

Dr. Tricot: I think it’s a quantity problem. If you have high risk disease, you have more of those cells that have the features of cancer initiating cells. If you have more differentiated disease, you have less of those cells and less of those cells are easier to eradicate than more of those cells.

Jenny: So in treating high risk disease, one of the primary objectives sounds like it’s to debulk that tumor burden or get rid of most of the tumors as much as possible.

Dr. Tricot: I think one of the key issues and unfortunately not appreciated adequately is the fact that if you have high risk disease that it’s extremely important to get to the most intensive treatments as quickly as possible. While it’s okay for patients who have standard risk disease or intermediate risk disease to have four to six months of induction treatment to try to reduce the tumor burden prior to transplantation. This is probably not a good approach in high risk disease. During those induction treatments, you risk that those myeloma cells acquire more mutations and will become more resistant than they were in the very beginning. You want to try to hit them when they are still extremely naïve and have no idea what’s coming to them.

Jenny: Now, let me ask you a little bit about testing because I know that the MyPRS test was created at the University of Arkansas and it’s used for genetic profiling. And then you start hearing about next generation sequencing or RNA sequencing, things like that. How does that fit in with what’s coming next? Is it a test that will evolve or is it an additive type of profile?

Dr. Tricot: I think if you want to test risk and see whether patients have high risk or low risk or intermediate risk that the best approach is still gene expression profiling. If you want to see how many clones are around and whether the clones have changed over time, then the next generation sequencing becomes more important.

Jenny: Because it’s hard for a patient to understand how to differentiate that. Most of the time your doctor is not bringing that up with you because you’re pretty confused anyway. What are the therapies that you consider to work best today for high risk disease? And then we’ll talk about futures in a little bit.

Dr. Tricot: So just like with standard risk treatment, the best treatment is still a more aggressive approach with, in our opinion, tandem transplants and maintenance therapy. While that type of treatment can eradicate the disease completely or at least keep it under control for long periods of time in a large majority of patients with standard risk, it cannot do that in the high risk patient. So once we have debulked the disease and we have eradicated 99.9% of all the myeloma cells, then instead of giving our regular maintenance therapy, here we will need to give either our regular maintenance therapy plus treatment that specifically targets myeloma stem cells or just myeloma as stem cell targeting treatments only, and that’s something that we’ll have to find out over time.

Jenny: And what do you consider to be the stem cell targeting treatments?

Dr. Tricot: Stem cells have different characteristics than the more mature myeloma cells. For example, embryonic stem cell genes are typically seen in myeloma stem cells and not in the more mature cells. There is an increased signaling pathway of Wnt pathway, the Hedgehog pathway, the Notch pathway, which we don’t see in the more mature cells. The more mature cells are also more sensitive to chemotherapy, to our regular drugs. The stem cells are more resistant and the stem cells can propagate the disease in mice while we don’t see that with the more mature cells unless you give millions of those cells.

Jenny: Like the quantity problem that you talked about earlier. What about new drugs that have just come out? We just had elotuzumab announced and daratumumab announced and an oral version of proteasome inhibitor, ixazomib (Ninlaro). What do you see about the use of the new drugs in the high risk setting specifically?

Dr. Tricot: What we don’t know at this point in time is the role of the monoclonal antibodies especially of CD38 antibodies such as daratumumab in terms of trying to kill those cells, whether they can kill myeloma stem cells effectively or not, whether ixazomib is going to be a major advantage in targeting stem cells, I would doubt that.

Jenny: Because it’s a proteasome inhibitor.

Dr. Tricot: Exactly.

Jenny: That’s in a similar class to the ones that exist already.

Dr. Tricot: Exactly. The only advantage is it’s going to be given orally which is for many patients a major advantage.

Jenny: I went to the session last night where they were talking about the difference between elotuzumab and daratumumab and where you might use one over the other. They were saying that elotuzumab, because it’s approved this way, you might use in the first relapse setting while daratumumab you might use in the secondary relapse. I guess you have to have three prior therapies, but that could be kind of anything. So do you see any favoritism I guess for high risk patients and using either one or one over the other or it’s just not that far along yet?

Dr. Tricot: My gut feeling is that daratumumab will be better for high risk patients and that is based on the fact that CD38 is much more highly expressed on myeloma stem cells that elotuzumab (CS1), and therefore will still kill those cells more effectively than elotuzumab. Again, this is all based on flow cytometry but we don’t have the actual clinical data to substantiate that.

Jenny: I went to one of the Friday symposiums and Dr. Giralt was talking about transplant. He was kind of surprised that only 45% of patients go to transplant. And then he talked about results from Dr. Cavo that compared single versus the tandem. And he was saying to a group that typical does one transplant and he knew that. He was saying this may require us to think differently about the tandem transplant. With high risk disease, what treatment options that exist today and then that are coming are the most promising in your mind for high risk patients?

Dr. Tricot: One of the differences between high risk and low risk patients, although in principle we treat them equally, is that high risk patients you have to give all the treatments on time while if you have standard risk patients you can afford for those patients to fully recover from their first transplant before we give the second transplant. But maximal tumor debulking with tandem transplantation and making sure that all the patients get their treatments on time is the key to success in high risk myeloma.

Jenny: So it’s just being timely and watching it really carefully.

Dr. Tricot: Yes, and not being afraid of even if patients have not fully recovered to go ahead with the further treatments.

Jenny: Because you don’t want it to get away from you.

Dr. Tricot: Exactly.

Jenny: That makes sense.

Dr. Tricot: High risk myeloma in contrast to low risk myeloma cannot afford long periods without any intensive treatment.

Jenny: Now, when it comes to something that’s high risk like a deletion 17, I know there have been some studies that show that bortezomib might have better impact if you do a transplant or a double transplant if you use it upfront. Do you want to talk about why that works? I don’t understand why that might work.

Dr. Tricot: There are studies done in relapsed patients where they have seen that whether the patients have the p17 deletion or not, that those patients whether they had it or not had equally long time to progression as patients who did not have the p53 mutations. So the general idea is that if you have a p53 mutation, you’re much better off with a proteasome inhibitor than with an IMiD and that IMiDs may actually be counterproductive in those types of diseases.

Jenny: Oh, interesting. So finding the right combination is so challenging. So when you split it up and you look at these genetic mutations like deletion 17 or 1q gain or the 4;14 translocation, how is it progressing to treat patients individually.  I know you always treat patients individually and look at their status and their goals and their disease and everything, but is the field to the point where you say, okay, for 4;14 patient, I would really prefer to do this protocol or combination or induction therapy or maintenance therapy. How do you make that determination?

Dr. Tricot: So if we have high risk patient, we try to get them to transplantation as quickly as possible. We’ll only give one induction treatment to get stem cells. Otherwise, you cannot do the transplant but as soon as we have the stem cells get them to transplant, do the transplants with an interval of no more than two and a half months apart and then the maintenance therapy needs to be two years of proteasome inhibitor, not with IMiDs like we do in the other patients. In our typical low risk patients, the second year will not have a proteasome inhibitor. In the high risk patients we always get two years of proteasome inhibitors and the second year without any IMiD.

Jenny: And a lot of people are talking about lenalidomide maintenance for a long period of time until disease relapse or something. So you’re saying that having something like Revlimid as an iMiD for long-term maintenance you’re saying might be counterproductive to high risk patients?

Dr. Tricot: Well, in Total Therapy 2 – which was a randomized study between intensive treatment with thalidomide and intensive treatment without thalidomide. The thalidomide arm was better in all groups except in the group that had high risk disease and was on thalidomide. Actually, that group did worse than the ones that had high risk disease and were treated with transplantation and maintenance therapy without thalidomide.

Jenny: Okay. Well, that makes sense. So as you look at ASH and you’re here for many sessions and it’s a place where people come to learn what others are doing in the community and the whole immunotherapy world seems to be opening up, what do you see as the future of that use and what looks the most exciting to you?

Dr. Tricot: Well, the most exciting is the monoclonal antibodies having been approved so quickly and will probably become a standard in any induction and maintenance therapy in the near future early on in the treatment of myeloma. And then there’s also a good hope for checkpoint inhibitors trying to get the immune system to do what it’s supposed to do, eliminate the little bit of disease that still remains after transplantation instead of the myeloma cells being able to paralyze the immune system so that immune cells cannot do what they are supposed to do.

Jenny: So when you have a lower tumor burden and you’ve kind of wiped most of the disease out and you want the immune system to regenerate and start over and be able to kill – because most people have these cells in them that are potentially cancerous and their immune system just knocks them down. Can you explain checkpoint inhibitors and how they work?

Dr. Tricot: So when myeloma cells and any type of cancer cell does not want the immune system to recognize them and kill them, they produce certain cytokines and products that will paralyze that immune system so that they cannot do effectively what they are supposed to do. One of those mechanisms is the fact that myeloma cells and other cancer cells have PD-L1 on the membrane which paralyzes the immune system. When you inhibit PD-L1 so that this paralyzing component is inhibited and gone, then the immune system can again do what it is supposed to do. However, we always have to remember that immunotherapy can only kill limited amounts of cancer cells. So to think that immunotherapy will kill all the myeloma cells up front when we have billions and billions of myeloma cells around is an illusion. Those treatments are going to have their best effect after there has been a major debulking and the best way to have major debulking at this point in time is still by transplantation.

Jenny: I heard that said about cancer vaccines for sure. I know I’ve been talking to some of the doctors that they say they’re using immunotherapy in combination with the standard transplant that it kind of empties the glass out and then even when they give back like the MILs therapy that Dr. Borrello is working on or other different immunotherapies that it kind of cleans the slate per se so that your immune system can ramp back up. Actually, having the transplant is an advantage sometimes because you’re regenerating these lymphocytes, right? Your body naturally regenerates a certain number of lymphocytes and gets it back up to a standard level. So when they’re giving this immunotherapies after transplant, then they can expand even more than they normally would if they were given alone. That’s some of the rationale that I have been hearing but maybe you have more comments about that.

Dr. Tricot: Well, when we talk about the immune system, we need to differentiate between the T cells which are most potent immune cells and NK cells, which can kill cancer cells without being educated specifically towards a cancer cell antigen. T cells in myeloma are very difficult. They are not very functional and it’s very difficult to deal with them. I have more hope for treatments that rely on immunotherapy that are using antigen presenting cells with monoclonal antibodies to eradicate the disease especially NK cells with monoclonal antibodies.

Jenny: Okay. So that’s the most exciting thing that you’re seeing out on the show for and in the sessions.

Dr. Tricot: Yes. And there is a special time post-transplantation where NK cells are not inhibited. Normally in steady state and K cells are inhibited from killing our normal cells or otherwise we would all die because of our own NK cells. But post-transplantation there is this short period of time which starts about three weeks after transplantation and it’s certainly over by three months but somewhere in between there’s a time where NK cells can really function very well without a lot of inhibition and can do what they are supposed to do. That would be the ideal time to introduce monoclonal antibodies to get the maximal effect of those agents and to mop up whatever has remained after transplantation.

Jenny: What do you think can be done to improve work or research for high risk? And then maybe you want to share the research that your group is doing.

Dr. Tricot: Well, we need to start with a clean slate in high risk disease. Whatever we have tried before has obviously not been extremely effective. And we need to develop treatments that we first test in mouse models of myeloma and subsequently if they work there, try clinical situations. And that will take time. Obviously, the community always wants to have something that they can get within the next two or three months but I think that’s a total illusion. If we want to eradicate high risk disease, we need to have time and we need to have the appropriate models to see whether what we think is working will indeed work in mice and then we can start to give it in humans.

Jenny: Do you want to talk about the work your group is doing also?

Dr. Tricot: Our group has focused on MAF translocations and we have seen that one of the consistent findings in those patients is that they have high Notch 2 expression. There are now monoclonal antibodies becoming available that can block Notch 2 effectively and selectively. You don’t want to have antibodies that block all types of Notch because Notch is necessary for many, many different functions in normal stem cells not only in myeloma stem cells. So you have to have a specific antibody that can block Notch 2 and that’s what we are trying to focus on.

Jenny: So what does Notch 2 do?

Dr. Tricot: Well, I don’t know whether you’re familiar with the concept of addiction. It seems like the more aggressive the disease is, the more the disease is addicted to certain microenvironmental and other factors being present and they can only grow and they can only function when the addictive factor is present. You can take advantage of that by blocking that pathway or that molecule that basically allows those cells to continue to grow. Take away their addiction and the cells will die. That’s what we hope will happen with blocking Notch 2 because Notch 2 is clearly high in patients with the MAF translocations. And if you put in Notch 2 in cells that are have low Notch 2 expression and you overexpress Notch 2, you can see that these cells acquire the same features as cells with the MAF translocations.

Jenny: It seems like it’s hard because this disease is not the same. It’s not the same disease. So what you’re doing for the MAF translocations like the 14;16 and 14;20 that you’re not looking at that for the deletion 17 patients and vice versa. So that presents a great challenge to researchers and the field in general.

Dr. Tricot: Yes. I think there must be different mechanisms that play a role in p53 in the 17p and 13 deletions. Usually, we don’t see them a lot early on in the disease. It’s something that typically comes later on. Our overall goal is to try to cure the disease up front before all those additional things that make it much more difficult to eradicate the disease start to show up. And that’s why giving long induction treatments and then allowing these things to mutate and to come up and become more consistent is, in my opinion, not a good approach especially not in high risk patients. But at this point in time, our feeling is that MAF translocations are still the highest risk except for the deletion 17 which is usually a later phenomenon but that there is more high risk in MAF translocations and in the 4;14 translocation.

Jenny: And is deletion 13 considered a high risk feature? Because I’ve heard you say maybe it’s not and maybe it is or…

Dr. Tricot: Well, we need to distinguish between deletion 13 as we find by FISH analysis which is present in about 50% of the patients and deletion 13 as we see in metaphase cytogenetics which is present in about 17% of the patients. So one in three patients with deletion 13 by FISH will also have abnormal cytogenetics with deletion 13. It’s only the subgroup that has the cytogenetic abnormalities and the FISH abnormalities that is doing poorly. The paitnets who have the FISH abnormality but don’t have the cytogenetic abnormality do equally well as the patients who don’t have deletion 13.

Jenny: Okay. I never knew that. That’s really fascinating.

Dr. Tricot: Also, it’s not the deletion 13 per se that causes the problems. What causes the problem is that deletion 13 is very often associated with 4;14 translocations, 14;16 translocations and 14;20 translocations. But these translocations cannot be seen on metaphase cytogenetics. You typically have to do FISH to detect those translocations. So in the absence of FISH, the only way we could see where there was a high risk of having one of those bad translocations was looking at chromosome 13.

Jenny: Oh, I see. So that’s why it was kind of broad but now it’s not really broad. Okay. Well, that makes a lot of sense. So to summarize your approach, you’re saying if a patient presents with high risk features, they just need to get immediate treatment. It’s not do induction therapy for 4-6 months and see how that goes and then go to transplant. If they don’t respond, it’s just get the job done as soon as possible.

Dr. Tricot: We think we have found the marker for myeloma stem cells which we are now testing in one hundred newly diagnosed patients to see whether we can find that population consistently and whether we can continue to find that population during treatment. Our expectation is that this will be an extremely small part of all the myeloma cells, less than 1% in the beginning but when you treat and you give your intensive treatments and more and more treatments that percentage will go up. All the sensitive cells will have been eradicated by the treatments and what’s remaining is stem cell pool. We expect that in some patients, we will not find them at all and those will have a very high probability of being cured. In other patients, we will see that percentage going up and up and up and those will be the patients that will ultimately relapse.

Jenny: This is a marker that you’re finding on flow cytometry?

Dr. Tricot: Yes indeed, on flow cytometry, and we have a lot of experience with cell lines and we find it consistently in all the cell lines. Now, we need to see whether we can find this marker also in real patient samples.

Jenny: And do you find that consistently across different kinds of high risk patients?

Dr. Tricot: Yes. We have looked at cell lines that have 4;14 translocation, the 14;16 ,14;20 translocation, deletion 17. The 11;14 translocation we find it in all those cell lines.

Jenny: Wow. And have you see the advancements in flow cytometry help with what you’re tracking  — because I know flow has added colors and more sensitivity. Is that part of all the MRD testing that we’re always hearing about or it’s just the standard flow test?

Dr. Tricot: In the typical MRD flow is you look at what markers are present in the beginning. Once you know what your markers are for your myeloma, then you follow those markers and see whether they disappear with treatment. And if they are gone, then you call them MRD negative. The key issue there is that you need to have a good bone marrow sample to do those tests and that’s usually where the test fails. If you use the fifth or the sixth pull of a bone marrow and it’s so diluted by peripheral blood, you may not have an adequate sample to do any testing of MRD. What we are referring to for the myeloma stem cells is a set of eight markers; one, the marker that we have and then seven other marks that we think are highly likely to be present on myeloma cells and then see whether we can identify that population and what other markers are going together with that one marker that we think is critical.

Jenny: Okay. So you’re tracking something that you think might indicate who’s likely to relapse and who isn’t.

Dr. Tricot: Yes. And how long the treatment will have to last. We hope that if we don’t find any of those cells in two or three consecutive bone marrows that we can say that we have eradicated or we need to eradicate we can now stop the treatment while for the patients who still have those abnormal myeloma cells after two years or maintenance therapy, we will have to give some continuing treatment until we get rid of those cells. Otherwise, those cells will start to grow again and cause the myeloma to relapse.

Jenny: That’s fascinating. Now, how do you combine all of this new information altogether? Because to me as a patient, it’s very confusing to know when would you ask your doctor or about the immunotherapies versus the standard treatment and how your doctor will decide all of this. So you’re building on a layer of many years of experience and it’s easier for you obviously to know what to do when. But how do you as a physician put that altogether for patients?

Dr. Tricot: Well, I think patients still need to realize that there are proven treatments that are effective in a large majority of the patients and that the treatments that I have had the most success and the longest survival with the best quality of life are the ones that are combining tandem transplants with maintenance therapy which for us is not single agent but combination of a proteasome inhibitor with an iMid or a proteasome inhibitor with cyclophosphamide and dexamethasone for at least two years. Although some myeloma doctors say that the newer drugs alone will work. we have no proof that it will work and provide survival statistics that are equivalent to those results obtained with transplantation combined with the newer drugs. I think it’s a very dangerous approach that patients should not go into. Those approaches need to be checked in proper clinical studies.

Jenny: So you want to see some history?

Dr. Tricot: Yes. It’s easy to have a myeloma patient live one and two years. It becomes more difficult to have myeloma patients live for five years, seven years, 10 years, 15 years. We’d like to see many more studies that show outcomes at five, seven and 10 years but I don’t see too many of those studies. When we see published studies with the newer drugs, we see results after one or two and then a good study maybe three or four years, but that’s about all.

Jenny: It’s tricky to do those studies because you don’t want a 10-year study because then you take 10 years to write your paper or present your results.

Dr. Tricot: But that’s why we need to try to find a good surrogate marker for cure. A good surrogate mark is that once you have eradicated all the myeloma stem cells, you’re done with your treatment, then we would know pretty early on.

Jenny: Right. Are you successful or not?

Dr. Tricot: Yes, exactly. And then whether new treatment is working or not. Can it eradicate all those stem cells or not?

Jenny: So that’s your signal towards a cure?

Dr. Tricot: Yes.

Jenny: That’s my final question I guess. We’ve heard this word that we’ve never heard really in the community besides a very select few people have mentioned the word cure, at least when I was first diagnosed. Only maybe Dr. Barlogie and a few others like yourself had said, “We might be curing a percentage of patients,” but now some others are starting to talk about it. Where do you think that cure will come from?

Dr. Tricot: Well, with the treatments we have at this point in time, we can get at least the third of our patients to remain in complete remission for more than 10 years. If people have had 10 years of continuous complete remission, the risk of subsequent relapse is not zero but becomes very low. Nobody is going to convince me that if you can keep a patient in a stringent complete remission with MRD negativity for 10 years that there is no cure rate in myeloma. Our best estimate is somewhere around 35% of the patients that can get there. Obviously, that’s not enough. We need to get to at least 70% or 80% but at least it’s a good first step.

Jenny: Yeah. And it’s very helpful for patients. And it’s exciting to see people who are ahead of you in your treatment from a patient perspective that are out 10, 15, 17, 20 years. It’s really helpful.

Dr. Tricot: But you also have to remember that our treatments have become better and better. So there were fewer patients treated 20 years ago who get to 10 or 15 years continuous compete remissions, compared to what we expect without our current treatments. I think many more patients, probably 50% or more, now will ultimately get to the 10, 15 and 20 years compared to the patients we treated more than 20 years ago.

Jenny: Well, Dr. Tricot, thank you so much for joining us on Myeloma Crowd Radio so we’re very grateful for the work you do. Thank you so much for all you do.

Dr. Tricot: You’re welcome.

Jenny: Thanks for listening to another episode of Myeloma Crowd Radio. We look forward to having you join us next time to learn more about myeloma research and how you can become more involved.

 

 

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About Author

Jenny A

Myeloma survivor, patient advocate, wife, mom of 6. Believer that patients can help accelerate a cure by weighing in and participating in clinical trials. Founder of Myeloma Crowd, Myeloma Crowd Radio and the CrowdCare Foundation.

3 Comments

  1. It’s encouraging to see such progress. However, when I was diagnosed two years ago my treatment was all wrong according to this. I did six months of treatment before transplant, achieved vgp remission then relapsed after ten months of maintence. I did not learn I am high risk at first and did not have a second transplant. I am in a clinical trial at this time but am beginning to relapse again. I guess I’ve missed the boat. What hope is there for high risk patients like me if we have not been properly treated at the ctitical time in the beginning?

  2. Janet, your treatment was probably the standard for most of us, so don’t feel you got the wrong one at the time. I think it takes the short remission period to confirm high risk. My remission lasted about a year, so now I am probably considered high risk, but in the beginning, who knew? You did not miss the boat. You may not have gotten on the first one out, but there are more setting sail all the time.

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