CML: Treatment Advances

- So thank you everyone for joining us for the first of four sessions of the Leukemia Research Foundation's New and Emerging Treatment series. The topic of this session is CML, and we're joined by Dr. Paul Koller from City of Hope in Los Angeles, who will share some slides about the latest treatments in and research for CML and respond to questions from participants. My name is Lindsey Whyte and I'm the Director of Programs & Partnerships at the Leukemia Research Foundation.

 

- I'd like to take a moment to recognize the supporters of this series, AstraZeneca, Autolus, Kite, Merck and Pfizer.

 

- We're going to talk briefly about the Leukemia Research Foundation, then I'll introduce our speaker and get things underway. The Foundation's mission is to cure Leukemia by funding innovative research and to support patients and families. The Foundation has raised over $95 million to support its mission since our founding in 1946 and has funded research grants to over 700 investigators worldwide. Our support programs for leukemia patients and loved ones include information and resources, education programs, financial assistance, and a directory of other helpful organizations on our website.

 

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- So we're grateful today to have Dr. Paul Koller. Dr. Koller is an Assistant Professor in the Department of Hematology and Hematopoietic Stem Cell, sorry, Hematopoietic Cell Transplantation in the Division of Leukemia at City of Hope Comprehensive Cancer Center in Duarte, California. He is actively involved in clinical and translational research for the treatment of patients with leukemia. His particular focus is in developmental therapeutics in acute and chronic leukemia, including biologically rational targeted therapy and novel combination therapies. He is a primary investigator on numerous trials in chronic myeloid leukemia, acute myeloid leukemia, acute lymphoid leukemia, and high-risk myelodysplastic syndrome. Dr. Koller, thank you so much for joining us today and please let's get things started with an overview of the latest treatments, research and trials for CML.

 

- Thank you, Lindsey. So I guess we'll- do you see this, the slides now?

 

- I do.

 

- Okay. Oh, there we go. Okay.

 

- So I'd like to thank the Leukemia Research Foundation for having me to discuss Chronic Myeloid Leukemia- the New & Emerging Treatments in 2025. As Lindsey said, my name is Paul Koller and I work at City of Hope in Duarte, California. So this is my obligatory financial disclosure slide. I think we can just move on quickly from that and we can focus a little bit more on CML and how people get it. So I imagine that many people listening were either personally or kind of adjacent, personally affected in this way.

 

- So people present with CML actually typically with no symptoms at all. If they do have symptoms, maybe they'll say they had some fatigue, maybe they'll say that they were eating a little bit less, that they lost some weight, that they had some fevers and they had some kind of abdominal fullness in an organ called the spleen, which a lot of people had never heard of until they're diagnosed with CML. When they get a CBC, and this is typically how they're diagnosed, they have a very high white count, they can have a normal or high platelet count, and then they have these cells in their differential called basophils. And when we look at a peripheral smear, there's like all the cells, not just blasts and not just good cells, but like all the cells. Then we do a bone marrow, there's lots of cells, and I would be remiss if I as a hematologist when describing cells didn't show you cells. So in "a" here this would be a peripheral cell, and you can see the purple cells are all, they all look a little different. And those would be cells of kind of varying maturation number or letter B. The slide B is a bone marrow aspirate and it's just tons of cells, so there's no white in there. Typically, there's like white interspersed with pink and red. And here it's just pink and red, which is called hypercellular. When we look at the bone marrow, biopsy and aspirate. And C as in aspirate and on the aspirate here again the purple cells, which are the cells which are really white cells, you see, they all look a little different as opposed to with an acute leukemia, they'd all kind of look like clones. And so this is like hallmark of CML. And then really what kind of cinches or concludes the diagnosis is the presence of this thing called the Philadelphia chromosome. And here you have the karyotype and karyotype means all the, it's within a cell, it's all the chromosomes in a cell and it goes from one to 22 with X and Y. And these are all the cells. And if you see there's an arrow to nine and an arrow to 22 here. And the Philadelphia chromosome is the small chromosome 22. And we'll go to the next slide to kind of blow that up to look at this under a cartoon. And so this is what's going on. So you have a normal chromosome nine and a normal chromosome 22. And when the cells, when a stem cell happened to divide a part of chromosome nine kind of merges with the part of chromosome 22 and vice versa, you don't lose any genetic material. But what you end up having is this- what's called a fusion protein, a part of BCR and a part of ABL are fused together. And the way I describe it in clinic is it's like, and I'm looking up because the lights are up, but it's like being in a room with the lights on and the light switch doesn't work and that's where you get all those cells. And so our job is to turn the lights off sometimes. Next slide.

 

- So how do people kind of present with CML? What do we look at the beginning? So we just have to acknowledge that there are three phases of CML. There's the chronic phase, which is how most people are diagnosed and that we kind of talked about previously. But again, it's usually asymptomatic. Occasionally there's some fatigue, sometimes there's night sweats, there's weight loss. Usually people kind of like this, but then it gets a little too much. There's abdominal fullness which ends up being splenomegaly. And then on a CBC, there's elevated white count. And then when we look at the blasts, there's less than 15% with the next phase. There's an accelerated phase is really just like the phase between chronic and blast phase. And think of this like a yellow light, we'll kind of come back to this like traffic light concept later in the talk in in other spaces. But I guess we're simple. So, you know, we like lights and we like traffic lights and room lights and stuff. So I apologize if we're using kind of the same analogies over and over again.

 

-And then there's a blast phase and this is a really difficult disease state to be in. And it's really, it's incredibly challenging. So with all the progress we've made, and we're going to talk about a lot, we still like really struggle with blast phase CML, but that's where the blasts are greater than 30% and/ or there's blasts outside of the bone marrow and the spleen. And there are some of other things that are happening in blast phase. But I think the simple takeaway is more than 30% blasts. So when someone comes with CML typically and they're in chronic phase, typically the average is they have three to five years before they progress to accelerated and then progress to blast phase. And then blast phase without treatment is an acute leukemia and is fairly quickly fatal. Most people in the developed world are diagnosed in a chronic phase and are usually asymptomatic over and over again. We talk about this and then accelerated phase and blast phase, like the progression is like a continuum. It just, things slowly, slowly continue to get worse. There are an additional set of genetic changes. The blast count goes up, pain gets worse, fevers get higher, spleen gets bigger, et cetera, et cetera. And really the initial treatment goal is to prevent progression of blast phase CML. And that's really like when you initially see us, like that's our goal. That and making you tolerate therapy is really what we want you to do. If we can go to the next slide.

 

- So tyrosine kinase inhibitors for CML, I'm sure most of the people on this call are familiar with how important these are because this has like totally changed how we treat CML and I would bet that there are still people and perhaps maybe even on this call that were directly, that directly benefited from the imatinib approval in 2001. And it cannot be overstated how important this, this development was. And it's really like a modern medical miracle that we have Imatinib. Shortly afterwards we realized like this was, this was incredible, but there are still people that need more. So we developed dasatinib, nilotinib and bosutinib. These are the years that they were FDA approved 2006, 2007 and 2012 and they're now approved in all lines. So Imatinib and all the second generation TKIs are approved for all lines. Around the time of the second generation development, we realized that there was this specific mutation called a T315i mutation. It popped these drugs out of the binding pocket. And so Ponatinib was, was developed specifically for this mutation. It was approved in 2012 and it's approved in the third line and with this mutation. And then in the last five years or so, we've had this myristoyl binding pocket inhibitor called asciminib or Scemblix. It was first approved for relapse CML in 2001 and then last year was approved in all lines. It's active in the T315i mutation patients. And then there are other non- TKI therapies like interferon, omacetaxine and transplant. And then to the left to the left is the, is this cartoon of the BCR ABL fusion protein with the ABL1 binding pockets, the ATP binding pocket where bosutinib, dasatinib, imatinib, nilotinib and Ponatinib are bind and then this myristoyl binding pocket of asciminib, which is like obviously a different, and I think it's important to note that it is a, it is like a new, very novel drug in that regard and it's something that we're very excited about in the field. Next slide. So CML and coexisting medical conditions. I think that when you meet and talk with your, you know, after you're diagnosed with CML and you're meeting with your oncologist or hematologist to talk about where to start, I think this is like where a lot of our thinking goes as to which drug to put you on. And a lot of it is the goal is patient concordance. So you know, we have five now frontline drugs and so we want to make sure that we are picking the best drug for you because actually no drug has been shown to improve the overall survival compared to imatinib. And so we look at all the comorbidities of the patient, including cardiovascular, diabetes, pulmonary, liver, kidney and financial. And I think we then look at that and then we will make a collective decision as to what the best drug is. And here is like a, it's an older chart looking at the comorbidity and the preferred preferred TKI and I say older because it doesn't include asciminib, but I think it's important because we haven't really worked out where asciminib goes. And so it stands alone in how we pick the frontline drug. And so I would imagine in the next few years or so we're able to sort that out. But in the meantime I think asciminib has its own benefits and its own issues that I think set it alone. Next slide.

 

-So we will then subsequently talk about milestones. And I really apologize for how this slide blows up, but I think you can get a sense of how much leukemia is in your body and then at different time points and different milestones. So if you look at what a CHR here is, a complete hematologic response, that's when your CBC or your blood counts are normal. I mean you still have a significant amount of leukemia in your body, even for a complete cytogenetic response, which is less than 1% of a PCR, you still have 10 times 10 to the 10th cells in your body. And that's why we need to continue treating you even with a complete cytogenetic response.

 

Now the great thing about a complete cytogenetic response is it's actually the most important milestone for long-term survivability, but you can still see that there's a lot of leukemia there for major molecular response. Again, this is the important milestone for thinking about a treatment-free remission. The timing of this major molecular response, and this is typical, a typical endpoint for, for clinical trials and there's still a lot of leukemia left. And even for a complete molecular remission, which is the CMR here, you still see a lot of, a lot of leukemia left. And so, you know, it just, this is an aside as to like how much we're missing even with quote undetectable disease and like the need to continue therapy until everyone agrees it's time to attempt a treatment-free remission. And this tells you why treatment-free remissions are not always successful even with patients with a complete molecular remission. You want to go to the next slide?

 

-So I've been alluding to response criteria milestones and here we're just, there's this thing called the NCCN and the NCCN is where a bunch of leukemia experts who get together and talk about the state of play for chronic myeloid leukemia. There's a physician part and there's actually also a patient part and I think Lindsey's going to give you a little bit more information on that later. But there are things for you and for us there's this nice slide here showing like where  you need to be at certain points. So, you know most people here have probably driven a car or seen a stoplight. So you could imagine that like green is go, red is stop- is not good. And then yellow or orange here or an orange maybe closer to red, but yellow is like in between yellow and orange. So over 10% at three months, like you want to make sure everything's going okay and then, you know, at six to 12 months where you get to like less than 1% and then here the light green is like you, you're going to be like good from a survivability standpoint, but you may not be able to stop the medicine. And then this like green, less than 1% is, you know, you could at some point think about like coming off of the TKIs. If you want to go to the next slide. So we've talked about coming off the TKIs and I've mentioned treatment-free remission, but this is the criteria stopping according to the NCCN guidelines. I used the 2024 because they had a nice little table, but it hasn't changed much. It, the table is no longer there, it's text so it doesn't port over to a talk as well. But discontinuation can be considered if you're over 18, if you had chronic phase CML, if you have a quantifiable BCR ABL transcript, if you've been on therapy for three years or more and you've had less than 0.01 for two years or more. And you can check the PCR on a like routinely. And actually that is one of the things that I find stops people from attempting a treatment-free remission. We can see in the next slide why that is. So the stopping criteria for, for, for stopping tyrosine kinase inhibitors in terms of how often we want to check it's monthly or every other month for the first six months, two every two months for months seven to 12 and then every three months afterwards. And then, and then you're, you, once you lose your major molecular remission, you need to, you need to check monthly until they're back in a major molecular remission and then check every three months afterwards. And really it's the checking monthly. Usually these people, usually the people that you're attempting TFR with have gotten used to taking the medicine every day and having their PCR checked every three to six months. So they really like that and they’re not looking forward to this like monthly checks and this unknown as to whether their leukemia will come back. But you know, the success rate is in the literature 50% with the following the guidelines that we have now and that 98% of people will respond after reintroduction if they fail. And then I think we usually guess about 20% of people can reasonably achieve this with, with our treatment approaches. Now we want to go to the next one. And so this is the first study looking at the long-term follow-up of a TFR attempt. And I really hate showing Kaplan-Meier curves to patients and Kaplan-Meier curves are these curves where you see survival and, months out. But, but here we'll just, it's pretty obvious like all the events happen at the beginning, this is why you check at the beginning and then once you get out after two months, nothing really happens and these people are probably cured, but we don't really know that and that's why we check them every three months really indefinitely. But this I think is the picture tells you when everything happens and which is, and, and tells you why we look so carefully right at the beginning. Next slide. And we are not going to talk about this in any detail at all, but I just want to tell you that when you've done your TFR and you've failed, you can try again. And we are doing studies showing that. So here's just a, like a, you know, a table with a few studies looking at this as the opportunity for a second TFR attempt. And so just know that you can do it again. So it's not, it's not just a one one chance one shot. Next slide. So, we'll this is where we're transition into like what's going on in the field. So we, we've really been refining two drugs at this point. A drug called Ponatinib and a drug called asciminib. And this is where we'll go into a little bit more detail. I think this is like the key slide from the Optic trial. And the Optic trial basically looked at doses of Ponatinib, what we learned with Ponatinib with the higher dose. We saw a lot of these arterial occlusive events and it's the reason that it's not approved frontline. And so, and we also found on with, with dose reductions that that the rate of arterial events was less. So the, this study basically did prospectively what we were seeing retrospectively and told us that if you start at a high dose and get like a deeper response to a BCR ABL less than 1% and then you lowered the dose to this 15 milligram dose Ponatinib was actually fairly well tolerated. And here are the response rates you can see like they hit 'em hard early and then lower the dose fast does seem to be the optimal dose. And this is what we have learned from the Optic. And we'll talk about this dose modification strategy later. It's something that we're really focusing on in the field, but we can go to the next slide. So asciminib, which is like the new exciting drug, The first, which is this myristoyl binding pocket inhibitor of BCR ABL, it's a novel, it's a novel targeted agent here, very exciting. And when compared to bosutinib in third line+ patients, you see it's, it was much better than bosutinib. There, you know, there are about 25, like 25% of patients achieved in MMR versus 13% on bosutinib. And then, you know, as that study wrapped up, we introduced a frontline study and again, I'm really sorry for showing like a curve. I like the bar graph's better, but yellow is asciminib and blue is everything else and it's the percent of people that get a BCR ABL of less than 1% at one week. And you can see that that asciminib got people to less than one, got more people to less than 1% than than the other TKIs. And that's a study called ASC4FIRST. If we go to the next slide, and this was presented at ASCO a year ago and then published in the New England Journal of Medicine as well. And then again here, I, I do apologize for this, but we will focus on the salient points here that the side effects with asciminib are better than all the other ones. And Lindsey, if you can just put the, for the asciminib grade three side effects, you can see there're 38% of all of at least one adverse event. And then for all comparitors, which is the last column for grade three, these are the clinically relevant ones. It's 49% and 38 is less than 49. And that's just what it is. And you can look at the rest of them here. But really I think that's the important takeaway. We'll go to the next slide.

 

-So where are we going, what's next? Like what do we have coming down the chute? Well we have a medicine called, and I'm really sorry for this- olverembatinib and I've said it like a thousand times at this point, but I always say it like that, but it's very similar to Ponatinib. But actually very interestingly is active in patients who have failed or are resistant to Ponatinib. And there is an upcoming phase three study that's going to look at this drug. It's actually already approved in China and it's very active.

 

-There's another drug called Vodobatinib that's similar to a second generation TKI, because it doesn't have activity against T315i, but it is also active. I'm not sure where we are from a development standpoint with this drug. And then there are three drugs with letters and numbers that are earlier on. There's TGRX and the TERN compound. Those are very similar to Asciminib and they're in phase one studies. And then there's this ELVN or ELVN 001, which is similar to Ponatinib is also in a phase one study. And so there are drugs coming, but they're relatively early in the developmental cycle. Next slide.

 

-So we're also looking into novel approaches and combinations. There's a lot of interest in lower doses with less dose interruptions, which may be better, more tolerable, less side effects, better response rates, et cetera. Asciminib, because it binds to a different binding pocket, allows us to think about combining TKIs. It never really made sense to combine imatinib with Ponatinib because they were competing for the same space. Asciminib and Ponatinib for instance, can in theory bind to the same molecule. And so that's something that there is a lot of interest in the field and then different targeted pathways as added addition to standard TKIs including like a JAK stat inhibitor like Jakafi, which has been of interest in the field for a while. And those, you know, there's always things coming out. There does not seem to be like a leader at this point in terms of that strategy. Next slide.

 

-And then I think that wraps everything up. I'd love to take questions and I look forward to hearing what we have to talk about.

 

- Great, well thank you so much for that. I think that was super helpful. I wanted to clarify one thing you said that Olverembatinib that, did you say that one's in a phase three trial or going into a phase three trial? Yeah. Okay, so that sounds like that's a good promising development for this group and something different from what we've seen. Yes.

 

- Yeah. Okay. Yeah, the phase one study was recently published and we're currently working on the registrational, similar to the asciminib versus bosutinib study we showed you earlier. Great.

 

-Okay. And then also you mentioned PCR testing and I just wanted to talk a little bit about that to make sure everybody understands what that is and why it's important. So I will mention, and I'm going to share my screen real quick, we do have some information on our website about various types of testing that are regularly done for patients. So this is a link to a page on our website, leukemiarf.org and then leukemia and then leukemiarf.org/patients/resources. And in those website pages we have some information on various testing and diagnostics. So I was wondering if you could just talk briefly about what do you, what do clinicians see in the testing and how is it helpful for you as you look at a patient going forward, whether they're in treatment or actually in treatment-free remission?

 

- Yeah, so that's a great question. And actually testing is something that has gone hand in hand with the development of therapeutics. So I showed you a karyotype because the pictures are nice and then there's fish, which is more accurate. So karyotype looks at 20 cells that are dividing and it, it's actually fairly onerous. You, the cells have to be dividing, you have to take them out. You have to culture them. You actually then have to look at the chromosomes and then you have to have a technician see where these changes are. There's  the next thing called fish and fish is the fluorescent in situ hybridization, FISH, that's where the fish comes from. And fish basically takes a red probe and a green probe and, when you have a BCR ABL, the red and the green probe becomes a yellow probe and you, they're like right next to each other. And we do that on 200 cells. So you can get like the sensitivity of one in a hundred, basically a one in 200. And that's where the cytogenetic response comes from. It's one, it's less than 1%, it's not an accident here. And then we develop PCR and PCR basically you have this long fusion protein and we cut at a specific spot and we amplify one way and we cut at another spot and we amplify the other way and we actually then look and see if we have like a short thing or if it just disappears into space. And if we have that short thing, and I'm using my hand here on purpose, if you have that short thing, it'll stack and we can count it. And so that's where the PCR comes from. That's where the number comes from. And that's typically when we're talking about TFR and these percentages less than 1%. That's where those come from.

 

-And the issue though is sometimes the BCR and the ABL fuse at a point where we don't have probes to amplify both ways. And you get these, less than 5% of CMLs are like this, but you get these PCR negative, but fish positive or karyotype positive, CMLs and those respond well to therapy, but the issue becomes how deep we can see the response and then when you get to a TFR, how you can do that because we want you to be way less detectable than you would be with a fish. And that's just not possible. Okay.

 

- Great. So as I said, if anybody has questions or wants some further information, they can look on our website to find some more information about those tests. And also I'm going to include a link in the chat to the NCCN guidelines for patients and caregivers so that you'll have it if anybody on the call who wants to learn some more. I highly recommend those guidelines because as Dr. Koller mentioned, the NCCN has a panel of experts who get together regularly and discuss the latest in treatment and develop guidelines for treatment for clinicians. And then from those guidelines for clinicians, they develop guidelines for patients as well. So you can see the information about what we just talked about, about testing and about symptoms and severity, et cetera. And also some questions to ask your doctor. So I think NCCN guidelines are a very good resource for patients and caregivers.

 

-So I wanted to ask a quick question that was submitted through registration that was specifically focused on adolescent onset of CML. Can you share a little for patients that are maybe younger, either pediatric or young adult patients, do you look at those patients any differently? Are there any special considerations with treatment? That kind of thing?

 

- Yeah, so I have a large, I would say young adult panel. I'm not a pediatrician and so we'll focus on 18 and up. But I do think of them slightly differently. I didn't show this, but in a lot of talks I give I show a slide about your overall survival with CML and it's actually approaching the general population for your age. And so it's something that I really want to hammer home. When someone who's in their twenties is diagnosed with this, if we can figure out a way to get you to take your medicine every day then you can live as long as you were supposed to in the world where you did not have CML if you believe in that sort of thing, you know? And so really it's about getting them to take their medicine every day and then trying to figure out what their goals are. And what I mean by that is like we addressed this early after the education and after identifying the tolerance, or at the same time, do you want to have a family? Like we talk about family planning, we talk about fertility preservation, we talk about if you get pregnant, what happens, that sort of thing. I think that's like an important thing to talk about and it can be dynamic. Maybe the 19-year-old is not really thinking about it or not interested in it, but, you know, that that same person at 27 is, or 30 or so. And so that may be in the back of my mind that the answer that they give me initially is not the answer that, when we get to a point where that maybe is going to change, we're passing the point of no return. As long as you're on the pills, there's always an option. But really with transplant, I think your ability to get pregnant afterwards is not, and transplant in CML is the option of last resort. But that's something that we would talk about. We would, ongoing talk about the price of the drugs. Some of these drugs are very expensive actually. Then, some of them now are going generic. So imatinib is generic and dasatinib is generic. If we think that this person, you know, a lot of young people want flexibility in their life. They may not be insured all the time. They want to be 20, they want to be in their place, live their lives. And so you know, it's great now that we have two really good options for people without insurance or that that doesn't require insurance. That's like a fixed cost that's not going to go up. That actually does seem to go down, you know, imatinib is $50 a month. I've actually seen that it may, I need to recheck, but it may be even cheaper on some like, non-insurance options. And so I think we take that all together when making the decision. So yeah, it's a huge consideration and it's enormously important when having these discussions. But I think, you know, establishing a rapport, integrating yourself into part of the team, making sure that we really address the most important thing, which is not progressing to blast crisis and getting them to take their medicine every day is something that we work very hard on.

 

- Okay. And as far as the drugs that are in development that you were talking about and you know, the ongoing tests for asciminib for example, you talked about how we're still trying to figure out how they work and that would be these longitudinal studies where you follow patients for a while who are on trial to determine if there are any adverse issues that come up or that kind of thing.

 

- So Lindsey I think there were two questions in there maybe, and correct me if I'm wrong, but one was like, one was like the novel, there's that list of five drugs that I listed as novel therapies. So the way that drug development works is that you identify a need and then you test compounds at various stages. So phase one would be really making sure that the drug is safe and there should be some activity. But really the primary goal of a phase one study is safety. And so like it's just basically for some of these testing increasingly higher doses of the drug to make sure that there isn't a safety signal that is important. And then typically when you get to like the highest doses there should be some activity in CML and there should be a sense of activity and these patients typically have exhausted all their options. And so if there's activity that's either this or stem cell transplant. So they're in various states of development, so like the TERN, the TGRX and the EVLN compound, those are in phase one studies. So really the focus is on safety. The olverimatinib is through the phase one and there is a recommended phase two dose. And the phase two is where you see some activity, but they're going to just go right to the phase three study. You know, there is a lot of activity with that drug. I have personal experience with it. And so we're going to see if it beats the best available option out there where we're looking at efficacy.

 

-Okay, asciminib was recently approved in the frontline. It was approved third line and above and in T315i setting. But when a drug is approved, we acknowledge that we don't know everything. And so there are still studies ongoing where you look at dosing, like whether it's good in the second line, you know whether it's good in other diseases entirely, you know, blast phase, whether it's good in different combinations, you get a chance to look to see it in other settings so that we can provide that option to patients in other settings. And I mentioned Asciminib is standalone as the first line. And the reason I think the field feels that way, and I'm kind of speaking for the field here, is that the data that came out of ASCO and was published in the New England Journal of Medicine and I actually showed it to you, the efficacy was better and the short term safety was better, but there wasn't long-, all this was short-term and this is like CML's a marathon play. It's not a sprint play. And so there's not long-term data yet. There's short-term data that's been good as a surrogate for long-term data, but there is not long-term data yet. And, from a safety standpoint, there's not long-term data. There's not long safety data. So we can tell you people have been on Imatinib for 25 years now. And so we can tell you that for, you know, a third of someone's life being on Imatinib is going to do this. We can't really tell you with these other drugs. And I think that's where you want to, you kind of have to have the conversation with people. It becomes a shared process and then the prices, let's not ignore the elephant in the room. The price is more. And so the perfect drug that you can't get is never better than the good enough drug that you can always get. And so you want to make sure that people get what they need, you know, you personalize it to them.

 

- Okay. Okay. We have a question here that was submitted online. I'm currently being treated with ponatinib. Would asciminib have been a better choice?

 

- So you, if you're having a good response, this how we feel in CML, if you're having a good response, the choice was correct. And if you're not having a good response, we should figure out how to get you to have a good response. So I can't tell you specific to your example, but I can tell you that I use asciminib a lot and I use Ponatinib a lot and I feel like they're both really important drugs for us in CML and no, assuming that things are going well, my guess was that Ponatinib was the right choice.

 

- We have, I know we have at least one person on right now who actually was not treated on a timely basis for CML and then her disease did change and she ended up having to have, I believe a stem cell transplant. And I just wanted to call out that even in those cases, patients can, you know, get the treatment they need and come back stronger than ever, hopefully. But you know, I just wanted to call that out, that these things happen. But really the most important thing is that the patient and the family of the patient actually said whatever's happening with our family member is not working and they went and found another option for her and that's when, you know, the advancement of the disease was recognized and she went to a more aggressive treatment. So maybe you could just talk a little bit - you kind of mentioned it earlier in the context of adolescents, but generally speaking, I think shared decision making is really important for this group of patients. You mentioned quality of life, you know, the importance really of talking to your care team, not just your doctor but also other members of the care team about, you know, what's going on in your life, the method, the type of medication you're taking, how regularly you're taking, and to understand if there might be some other options. Do you have any advice for patients and caregivers as they kind of navigate this, this road?

 

- Yeah, so, you know, I always spend a lot of time, you know, even if it's like a fifth opinion, I feel compelled to like explain to them at least my, the way that I explain CML because I think like once you understand like what's going on, like the rationale for like treating it with a pill that basically like, kind of like short circuits the zombies, just to borrow term, it makes sense. And then if it makes sense, people are more likely to like kind of do what's needed. And this is where like this is why shared decision making is important in this disease is because like I can pick the perfect medicine but if you don't take it then like we're not going to get anywhere. And so, you know, like I, I like, I feel like it's like kind of understanding what's going on like with the disease and then, and then always understanding the milestone. So like why are we shooting for this percentage and what's the point? What's the point of it? And what to look for? And so like we always, at least in my clinic, we always kind of come over to the computer and I show them the PCR and they have to look at it and we’ll say, you're less than 1%, that's great or you're less than 0.1%, that's even better. Or you're undetectable or that's amazing or you're not, you're over 1% - this is where we need to get you. Or, this is where you are on this road to where you need to be. And I think that's where making sure that   the person is comfortable with their team, that they at least have some understanding of what CML is and what we're trying to do here. And that they understand what our milestones are, what we're looking for to get them to this long life is really I think how I at least try to initially tackle it. And then everything else is like working out the details, like making sure the medicine is tolerated, you know, making sure that we have backup plans, making sure that we have all these things.

 

- And to be clear, some people might not be taking the medicine because it's not making them feel well, right? So, you know, maybe the adherence to the treatment is not because they forget it's because it's causing other issues, which is part of the reason. So to that end, actually I, I think we're going into the lightning round here because we have a couple of questions left and only a couple of minutes left. So one person asked what can help raise platelets and another person asked what can help with a queasy stomach from Sprycel, which I think is dasatinib, if I'm not mistaken. And then the last one is, how can we improve a very low red blood count? So I don't know if you can quickly respond to them?

 

- Okay, so we'll lump the platelets and the red cells together because those are cytopenias. So one of the things that I talk about when we're treating patients initially is I use a lawn [analogy] because a lot of people have lawns. I guess not in the southwest, most of it's dirt now these days or sand. But people have lawns and so like if you look at a lawn from a helicopter, if it's green, you don't know what it is. It could be weeds, it could be grass, but when you look closely, a CML lawn is weeds and initially we rip out all the weeds and we're left with dirt and the grass has to grow and it takes some time. Sometimes the grass grows back really fast, but sometimes it grows slow and those are cytopenias. So we have to dose adjust the TKI, we have to hold the TKI, sometimes we have to give support blood transfusions, a medicine like promacta to help the platelets come up. But there's all these things that we can do, but like eventually we gotta get rid of the weeds or the weeds are going to grow into the house and affect the house, the foundation and the walls and stuff. So it's actually really hard to a subset of people, these cytopenias and some people, they need to get a transplant because of the cytopenias. As for the queasy stomach, talk to your doctor about supportive care that you can get. Like there's medicines for nausea, there's timing of the day of taking the medicine, you could lower the dose if you're having a good response and then sometimes you just have to switch. I mean we're kind of acknowledging that after exhausting a lot of trial and error that sometimes you just have to try a different medicine and that and the medicine that you try- you'll have more options if you're having a good response. So I think that's the real takeaway for you is you don't need to live with it forever, but please take your medicine until you all come up with a plan to hold, reduce, support or change.

 

- Okay, great. We did get a couple other questions come in just in the last minute or two, but unfortunately we've run out of time. But I'll try and share those with you if we can maybe get some information back to those people directly. But, in the meantime, I just wanted to thank you so much for your time and effort and for putting together a great presentation. I think it was super helpful. And one last time also to recognize the sponsors of the program and encourage anyone who is interested in any more information, we have three more programs coming up- one tomorrow on CLL and then, next week, we have AML and ALL. So you can go to our website to register for those programs as well. And as I mentioned at the beginning of the program, please do look out for the survey link to give us some feedback on this. We really appreciate everybody's participation, the great questions. And Dr. Koller, thank you so much. Any parting thoughts?

 

- No, thank you for having me. Thank you for great questions. And you know, the Leukemia Research Foundation is a wonderful organization and I really am honored and appreciate the opportunity to do this.

 

- Thank you. Thank you so much. Goodbye everyone. Have a great day. Take care.