CML: Treatment Advances 2026

New & Emerging Treatments in CML  2.25.26 Transcript

Participants:     Dr. Fadi Haddad, The University of Texas MD Anderson Cancer Center

Lindsey Whyte, Leukemia Research Foundation

 

Hello and thank you for joining us for the final of four sessions of Leukemia Research Foundation's 2026 New & Emerging Treatments series. The topic of this session is CML, and we are joined by Dr. Fadi Haddad from MD Anderson in Houston, who will share some slides about the latest treatments and research for CML and respond to questions from participants. My name is Lindsey Whyte and I am the Director of Programs & Partnerships at the Leukemia Research Foundation.

 

I would like to take a moment to thank our supporters of this series and this particular session. They are Autolus, Novartis and Cycle Pharma.

 

The Leukemia Research Foundation's mission is to cure leukemia by funding innovative research and and supporting patients and families. The foundation has raised over $95 million in support of our mission since our founding in 1946 and has funded research grants to over 750 investigators worldwide. Our support programs for leukemia patients and their loved ones include information and resources, education programs like today's financial assistance, and a directory of other helpful organizations on our website. For today's program, all participants will be muted, but we welcome your questions in the Q & A box at the bottom of the zoom screen. Please note that if you submit a question, your name will show unless you click the little button at the bottom, the little box that says anonymous. So if you don't want your name to show, make sure you click that box for the anonymous question. If you already submitted a question through the registration process, please know that we have those questions and Dr. Haddad has seen them and he will be incorporating responses to some of those questions through the course of his slides that he presents. We'll do the best we can to cover as many of the questions as possible. After today's program, you will be sent a brief, a link to a brief evaluation through email. We would be very grateful if you would take a moment to complete the evaluation so that we can improve our future programs. Also, this program will be recorded and a link to the recording will be sent to all registrants after the program.

 

So we are grateful to have Dr. Fadi Haddad with us today. He is an Assistant Professor in the Department of Leukemia at the University of Texas MD Anderson Cancer Center in Houston. With over 120 peer reviewed publications, Dr. Haddad has made significant contributions to the field. He has played a pivotal role in the design and execution of numerous phase three clinical trials, particularly in chronic myeloid leukemia where he served as a principal investigator. Believing that informed patients are empowered patients, Dr. Haddad actively promotes education through his YouTube channel and Instagram page where he regularly shares accessible evidence-based content on leukemia and cancer care. Dr. Haddad, thank you so much for joining us today. Please, let's get things started with an overview of the latest treatments, research and trials for CML

 

- Lindsey, Thank you so much. I would like to thank the Leukemia Research Foundation for this opportunity. As you mentioned, I'm a big fan of patient education, not only physician and community education, but I think patient education, caregiver education is extremely important, especially now that we all have access to a lot of data and there's a lot of updates coming. So it's very important that our patients and their caregivers are educated. And so what I'm going to try and do today is maybe do a 30, 35 minutes overview on leukemia and most of the recent updates and then open the floor to question and answer for our audience. I'm going to share a few slides here. Can you please tell me if you see the slides?

 

- Yes, we can see them if you want to make them bigger, that's perfect.

 

- Okay. They are from my end. Do they do full slide. Okay, perfect. So what, what is exciting in CML 2026, 2027 and beyond? Before we start, I'm going to just do a five to seven minutes background. As we all know, there's, there's multiple treatments for CML that are approved either in the frontline setting. As you can see, we have five different drugs that are approved for the frontline treatment of patients with newly diagnosed CML. In the second line, the third line setting, we have also many, many options whether clinical trials, FDA, approved drugs, transplant, and we also have some other drug that I'm listing below that kind of are adjunct to TKI therapy. Here I am summarizing the different tyrosine kinase inhibitors TKIs that we use for the management of CML. In the middle is a visual schematic of how the molecule or how is the kinase represented. In CML, we have basically two, two major sites. The site that is in white, which we call the kinase domain, it is targeted by the ABL1 kinase domain inhibitors. We have five approved Imatinib, bosutinib, dasatinib, nilotinib, and Ponatinib. And we have two others that are still in clinical trials, investigational, but very promising- olverembatinib and ELVN-001 and I will be talking about that today. On the right side, also, you can see allosteric inhibitors. Those are drugs that bind to the Myristoyl pocket, which I'm representing in green in the figure. And by binding, they also altered confirmation of this protein and block the progression of CML. Asciminib is the first allosteric inhibitor that was approved across first, second, and third line. And we have two others, TERN-701 and TGRX-678 that are also very promising under investigation in clinical trials. We'll talk about that today.

 

I added this slide because one of the comments or question I got was, what level of BCR should I have when I receive treatment for CML? So in the frontline setting, studies have shown that when we receive treatment, the BCR level or after one year of treatment should be less than 1% what we call complete cytogenetic response. Because when we achieve this level of remission, patients have a normal survival similar to the regular population. Now, if we achieve deeper levels, what I show in red here, deep molecular response, a BCR below 0.01%, then we can start talking about treatment-free remission and treatment discontinuation. And I will tackle this in a bit.

 

So let us talk about frontline therapy, and I'm going to share the slides later so you can give them to our audience here so they can take a closer look at that. But how do I decide on what is the best frontline treatment for a patient who comes to me with a newly diagnosed CML? So there are different criteria that we look at. Number one is the age of the patient and the treatment goal. If we have a young patient, maybe young woman that wants to conceive or maybe young patients that don't want to continue life long therapy and want to attempt a treatment-free remission, then I would favor second generation TKIs. Dasatinib is safe, easy to manage or asciminib the new STAMP inhibitor. But if a patient is maybe an older patient where we don't really focus on treatment discontinuation, but we focus on quality of life and survival, then may be imatinib or generic Imatinib is the drug of choice. So age, treatment goal, number three is the cost of therapy. We know that all these treatments are very expensive, although insurance supportive programs can help, but these are also expensive drugs. So if we have patients who do not have insurance, cannot afford to pay for these drugs, then we can use generic imatinib and through cost plus pharmacy, this cost $34 per month. So for patients who cannot afford out of pocket, still we can give them some treatment to normalize their survival. What about risk score? We know that we classify CML according to different scoring systems between low risk or intermediate risk or high risk. If a patient is low to intermediate risk, basically we can use any of the TKIs available. If a patient has high risk disease, I would favor second generation TKIs or asciminib.

 

What about comorbidities? I'm not going to go into the details, I'm going to share the slides later. But to know that every patient has a different comorbidity profile, some patients have hypertension, some others have liver disease or kidney disease, et cetera. So according to each comorbidity that the patient has, we can tailor the TKI that is best indicated in that particular situation and mostly or more importantly, avoid some of the drugs that could be toxic in these scenarios.

 

One of the questions also came regarding treatment discontinuation, treatment-free remission, or TFR. Briefly to know there are many, I would say guidelines. The two different guidelines are the first one patients need to be in a deep molecular remission, a BCR below 0.01% for two years or longer. In this situation, the cure rate is close to 40 to 50% and there's still always 50 to 60% risk of relapsing after the patient stops therapy. Now at MD Anderson, we adopt a different approach. We tell our patients that once you achieve a deep molecular remission, I would like to see it sustained not for two years or three years, but sustained for five years or longer. And this gives me higher chances of telling my patients stop treatment and being confident that the leukemia is less likely to relapse. As you can see in the blue curve at the right side, those patients who achieved a deep molecular response for more than five years, their TFR rate exceeded 80% compared to close to 60% in those where the duration of remission was lower than five years.

 

Now, how to manage patients who have intolerance or side effects from the drug. Very important take home message here today. If a patient is receiving a frontline therapy and they develop side effects, I don't recommend switching to a different drug. I recommend first reducing the dose of the TKI from like 400 to 300, from 100 to 50, et cetera, before considering a switch of treatment. Because many times a dose reduction could be enough without exposing the patient to new toxicities and a new drug.

 

Here is a different table. I'm not going to go into the details, but if we focus on the column labeled prohibitive toxicities, the column before last, those are toxicities where I do not recommend to reduce the dose. I recommend to change completely. There are some toxicities where we are okay in reducing the dose, but there are some toxicities where we should completely change treatments such as neurotoxicity, arterial occlusive events such as brain strokes, heart attack, et cetera, repetitive pleural effusions, enterocolitis or refractory hypertension among others. And again, I will share the slides so you can read all those in more detail.

 

Now what about resistance? So patients who have resistance to treatment and how do we define usually resistance? As I mentioned in the first slide, a BCR level that does not go below 1% after one year of therapy, or a patient who responds, achieves the cytogenetic or a molecular remission, but then loses the response again, the BCR starts going up, or they develop mutations. How should we decide on therapy? Every patient who has resistance, we should check for ABL1 kinase domain mutations and always tailor the type of therapy according to the mutation and always select the next TKI where the mutation is sensitive.

 

Now, if a patient now here an important point as well, if a patient is receiving either dasatinib, nilotinib, or bosutinib as first-line therapy, they have resistance, they progress, and we don't find any mutation, then what we should do? I don't recommend alternating to a second generation drug, but I recommend going to the more potent drugs which are Ponatinib and Asciminib because we know that patients who fail a second generation TKI, they do better if we give them newer drugs rather than rotating to another second generation drug. Now I'm going to discuss the more recent updates in the second line, third line and beyond. So what we have for our patients who have resistance to frontline or second line therapy, we have Ponatinib, which is a third generation TKI, that is approved for patients who failed multiple lines of therapy before, two or more. And as you can see, results from the PACE trial showed excellent survival at five years, 73% in patients who are resistant, intolerant have T315I mutation. Now this drug is very toxic. That's why it can lead to cardiovascular disease, brain stroke, pancreatitis. That's why the second trial here, the OPTIC trial, I'm not going to go into the details, but the summary is if a patient is receiving Ponatinib at 45 milligram per day or 30 milligram per day, they should continue to check the BCR test. And once the BCR hits 1% or less, the patient should have the dose of Ponatinib reduced to 15 milligram per day to reduce the risk of cardiovascular toxicity, primarily.

 

Asciminib is also approved in the second line and also in the third line. Here I'm showing the study the ASCEMBL trial where Asciminib was compared in the third line setting versus bosutinib in patients who failed the prior therapies. Again, we see here better molecular response rates with Asciminib as you can see in red, 29% compared to 13% after close to one year of therapy. However, if we look in red here, there was no difference in survival. The two year overall survival is 97% with asciminib and 99% with bosutinib. What this tells us, this tells us that the new drugs that are coming are very effective. They are sometimes less toxic, but they are more effective. They improve the molecular response rates. But today we have a lot of treatment options, a lot of clinical trials, bone marrow transplant. So at the end, patients are having almost a similar and very good survival.

 

So now I'm going to talk for the remaining of the presentation about the four drugs that are new. These are kind of what we're going to expect in 2026, 2027. Those will eventually lead to new approvals and new treatments for our patients. I will start with ELVN 001. It is similar to Ponatinib. It is a third generation TKI. It was evaluated in the ENABLE trial. It's a phase one study of patients who were previously treated with different TKIs and they received this ELVN. And since this is a phase one study, we went in a stepwise fashion on the dosing, as you can see from 10 milligram to 80, even one 20 milligram. And we looked at the safety and the efficacy of this drug. So in this study, at least this is the latest update from September, 2025. We have enrolled more patients since then, 90 patients in total. As you can see here, I put them in a box in blue. What were their baseline BCR::ABL transcript before they started, more than half of the patients, 52% had resistant disease, had a BCR to start with of more than 1%. 9% of the patients had evidence of T315I mutation, which we know is one of the most resistant mutations in CML. If we go to the table to the right side, we can see that 32% of the patient received one or two drugs before getting ELVN. 41% received three or four drugs prior to ELVN and 26%, almost a quarter of the patients received five drugs or more. So again, heavily pretreated patient population. 58% of the patients did get asciminib before ELVN and 43% did get prior ponatinib. Now if we look at the why, patient went to receive ELVN 72% because they lacked efficacy to their prior treatments and 23% because they had side effects to the prior therapies.

 

Here I'm going to show the side effect profile of this drug. I have many patients treated with ELVN 001. I can say that this drug is overall well tolerated. Most of the patients complain of maybe some joint pain on blood tests, show and drop in the platelets, some increase in lipase. But overall, this drug was very tolerated. Overall safe, as you can see here, those are the most frequent side effects, increased in the level of lipase, diarrhea, low, low platelets, joint pain, fatigue, et cetera.

 

What about the response rates? So we looked at the safety, let us look at the efficacy. So here we are looking at the rate of major molecular response or MMR or a BCR level below 0.1% by 24 weeks by six months of therapy. And if we look at patients who had baseline, they were not in a molecular response. The third of them, 32% went deep in their response achieved in MMR by six months. And all those who were in MMR remained in MMR. So overall, we had 50% of the patients who were in MMR by six months of therapy. Again, this is a heavily pretreated patient population who received multiple lines of therapy before. 32% of the patients who had prior Asciminib achieved MMR. 35% who had prior Ponatinib achieved MMR. And those who had prior resistant to therapy, 41% of them achieved MMR. We moved to the right side. What about CCYR or BCR below 1%. All those who had a PCR below 1% to start with before ELVN maintained that response. But those who were not in CCyR, those who had a BCR above 1% to start with, 52% of them deepened their responses and achieve their BCR level below 1%. So this tells us that this drug is really very active in patients with CML who are heavily pretreated who receive multiple lines of therapy, including Asciminib and Ponatinib. And this is in phase one. I think there's going to be a phase three study planned for maybe next year. Hopefully we can see some approval of this drug in the, in the next one to two years in the relapse refractory setting.

 

Now we move to the second drug TERN 701. TERN 701 is an allosteric inhibitor. It is similar to asciminib. Again a phase one study called CARDINAL study in patients who were previously treated with multiple TKIs. Patients should have received two TKIs or more, had failed because of side effects, because of resistance, and patients could have or have not had a T315I mutation. And again, to the left side, you can see is a stepwise approach because we're testing this drug in a phase one to see what is the best dose. And on the right side you can see that the, for the dose expansion or part two, we're deciding on one of two dose levels, 320 milligram or 500 milligrams. Let us look at the patient population, similar to what we did before. We start by patients who have a BCR level above 10% before starting TERN, 44% of the patients had a BCR above 10%, 13% of the patients had a BCR between one and 10%. So I would say close to 57, 60% of the patients had disease resistance, a BCR above 1%, even above 10%. 25% of the patients did not have disease resistant, had a BCR below 1%, but maybe they had some side effects. That's why they were enrolled on this study. If we go down, what was the cause of switching to TERN? Mostly lack of efficacy, according to the ELN criteria, 64% of the patients. Side effects 29% of the patients. Again, heavily pretreated patient population, 60% of the patients had received three drugs or more before receiving TERN. 38% of the patient had prior exposure to asciminib and 22% had prior exposure to Ponatinib. What about the mutations? Similar to the previous study where we had 9% of T315I, here we have 10% of the patients who had the gatekeeper resistant, T315I mutation.

 

What about safety? What about side effects? Let's look at the summary of all patients to the right side of the slide. Overall, as well, generally safe drug, some side effects that are manageable. If we want to talk about hematologic side effects, low platelets were seen in 16% of the patients, anemia in 10% and neutropenia in 13%. If we look at non hematologic side effects, we mostly have diarrhea in 21% of the patients, headaches in 19%, nausea, fatigue, some abdominal pains, some muscle pain, back pain, 10% elevation of liver testing ALT. So this tells us that between 15 to 20% of the patients we have some nonspecific symptoms, nausea, diarrhea, headache, some pain, which could be significant for the patients, but I don't think they are life threatening. But they can impact the quality of life of our patients. And that's why it is very important in the clinic for our patients, for our caregivers, mention this to your doctor. Maybe the doctors will ask mostly about maybe the more significant side effects like the fatigue, the diarrhea, but they might forget to ask about back pain, about skin rashes, about joint pain. So I encourage you to always raise any side effects to your physician and they can decide if this is related to the drug, yes or no. Not only about TERN, but about any other drug that you are receiving. And as we, and as we can look here, grade three or higher, it wasn't very, very much reported. 8% in hematologic side effects and maybe close to 2% in non hematologic side effects. So most of the side effects were mild to moderate grade one and two, high or severe side effects were not frequently observed.

 

There's a question in the chat and then we can come to it later at the end of the presentation. What about the response rates with TERN 701? The overall MMR rate was 74%, 64% of the patients who were not in a major molecular response, BCR below 0.1% at the start of therapy achieved MMR and all those who were in MMR maintain that response. Now let us look into different subgroups. This is all at six months of therapy. Patients who had lack of efficacy or resistance to the prior TKI, 63% of them achieved MMR. Those who had side effects, 71% of them achieved MMR. As you might expect, patients who have toxicities don't have as much resistance as others, so they tend to respond better. 43% of the patients who had the prior asciminib achieved MMR and 50% of the patients who had any other potent drug, ascinimib, ponatinib or ELVN achieved a response. So I would say between 50 to 60% response rate in patients who fail prior therapies.

 

Now we move to drug number three. This is called olverembatinib. It used to be called TGRX. Now we call it olverembatinib. It is a third generation TKI. It's similar to Ponatinib, it is similar to ELVN. It's a direct kinase inhibitor that is approved in China or has been approved in China many years ago for CML with very encouraging efficacy. So that's why we conducted a very large study in the United States of 62 patients who received olverembatinib. The difference between olverembatinib and other drug, it is given every other day. It's a pill. All of those are pills that it's not given every day, it's given every other day. And if you look at patients with CML in chronic phase, 81% of them had received three or more drugs before getting to olverembatinib. 50% were previously exposed to Ponatinib and 27% were previously exposed to asciminib. So I would really say heavily pretreated resistant patient population. If we look at the table, and again I'm going to leave you this for you to dig deeper into that, but I'm going to focus on the numbers highlighted in yellow. In patients who have T315I mutation resistant mutation, 56% of them achieve the complete cytogenetic response, BCR below 1% and 44% of them achieved MMR, BCR below 0.1%. So this is very encouraging result. Those who had resistance to prior Ponatinib, half of the patients 53% achieved CCyR, 43% achieved MMR. And those who had the prior asciminib 50% achieved CCyR and 33% achieved MMR. So again, in patients who are previously treated, the resistant, 40% of them almost achieved MMR and close to 50 to 60% achieved CCyR. Again encouraging results. And this study led to a big randomized study now ongoing in the United States, Polaris 2 the study is close to completing accrual. A total of 285 patients will be enrolled on this study. Again, CML in chronic phase who received two or more drugs before will receive either olverembatinib 30 milligram every other day or BOSUTINIB 500 milligrams per day. And the primary endpoint is the rate of MMR at 24 weeks. We don't have the results yet of this trial, but we'll have it sometime I hope in 2026 and we can see how the results compare.

 

And there's a part B of the study where they look at patients with T315I mutation in particular, those patients receive a slightly higher dose of olverembatinib, 40 milligram every other day. And again, we'll see the updated results on this one as well. Now I'm going to finish by the last drug, last drug that we have and then we can open it for questions and for discussions, TGRX 678, this is an allosteric inhibitor. It is similar to Asciminib and to TERN, so Asciminib, TERN, TGRX 678, we call them STAMP inhibitors or allosteric inhibitors. It was reported at the American Society of Hematology meeting 2024 showing promising activity in patients who have resistance with or results the T315I mutation.

 

So this, at this ASH meeting, they reported a separate analysis in patients who have chronic phase CML or accelerated Phase CML, but only having the T315I mutation. So I figured I'm going to include this because this is a more recent update and maybe many patients inquire about T315I mutations. So let us see. They had in total 53 patients where T315I mutation was identified and they received TGRX. Again, it's an oral drug. And as you can see to the left side, 10 patients had dose escalation, different various drugs, various doses of this drug from 20 milligram twice a day to up to one 60 milligram per day. And then they moved 43 patients who were treated in the dose expansion phase of the study. And two different groups. The first group chronic phase CML, one or more prior therapies and T315I mutation. The second group was not chronic phase, but accelerated phase CML one prior therapy with or without T315I. So this is the total patient population. 53 patients, 60% had chronic phase disease, 40% had accelerated phase disease. As you can see at the bottom part, most of the patients were not in a cytogenetic response at the time of TGRX treatment. Okay? So BCR mostly was above 1% in these patients. So failure or resistance to prior therapies, 79% had T315I alone mutation alone, 21% had what we call compound mutation or T315I with another mutation. 36%, a third of the patients, had received one or two prior lines of therapy. A quarter 23% had received three prior lines of therapy and 42% of the patients had received four lines of therapy or more. So again, multiply relapsed, refractory, pretreated patient population. Third of the patients 30% had received Ponatinib, 19% had received prior olverembatinib.

 

What about the responses here? I'm going to focus on chronic phase patients. So chronic phase patients, as you can see here at 24 months, two years on the green curve, we can see the rate of CCyR was 61%, not bad, remember those are resistant failing patients. Multiply pretreated, 61% of them achieved a complete cytogenetic response at two years. Very encouraging result. 45% achieved MMR at two years and these responses were durable, between 75 to 80% of the patients were already in continuous response at two years, as you can see at the right side of the curve. Now here, I think this is an important slide that tells us how patients respond to TGRX 678 based on the previous drug that they received before that. So if they received a STAMP inhibitor such as asciminib or TERN, for example, the purple curve, they don't achieve a CCyR at two months because those probably patient who failed an allosteric inhibitor, so it doesn't make too much sense to give them another STAMP inhibitor with the same mechanism of action. Those who received a third generation TKI like Ponatinib or olverembatinib for example, those did better 35% CCyR at 24 months. But the patients who were never exposed to Ponatinib, Asciminib, the newer drugs, they did better because those were possibly still more sensitive. And the CCyR rate at two years was 66%, Similar to MMR, the highest MMR rates were in patients who have not received any of the more potent new drugs, 12% in those who received third generation drugs and no MMR response at two years in those who were previously exposed to a STAMP inhibitor.

 

So very important that your doctor picks or tailors the type of therapy based on your response, based on your mutations and based on what previous therapy you have received. Because now we have multiple of drug approved or in trial. So it's always important to sequence these therapies and select the best drug for the patient based on their comorbidities, based on affordability, based on prior response, prior mutations and also very important as we can see here, prior TKI therapy.

 

So I'm going to leave you with this last slide clinical trials that we have here at MD Anderson for CML in chronic phase. So in frontline treatment we have asciminib monotherapy single agent, 80 milligram per day available to our patients on a clinical trial free of charge. So if you know any patient who are interested, cannot afford drug, we we have this clinical trial open free drug provided. We have another drug where we combine dasatinib with oral decitabine. It's an oral hypomethylating agent to kind of target the leukemia stem cell and improve the rates of treatment-free remission. We are analyzing this data now and we'll see if it's going to be better or not compared to single agent alone. And coming soon I think is a very exciting concept of dasatinib with ROPEG interferon. Ropeg interferon is a very long formulation, long acting, interferon because we know 20, 30 years ago before we had even imatinib, the treatment for CML was just interferon and we have had multiple patients achieve complete cytogenetic and even molecular remissions with interferon alone. But it was an injection that is given every day, very toxic. Ropeg interferon, commercial name is Besremi, is approved for myeloproliferative disease. So we are adding it to dasatinib in CML one injection every two to four weeks to kind of target the leukemia stem cell, maybe prevent relapses of the disease, improve the rates of treatment-free remission.

 

In the second line setting we have multiple clinical trials. We have olverembatinib, which is the newest, the new third generation drug and patients who failed frontline therapy we have Asciminib as well available. We have Ponatinib, we have ELVN 001, the new third generation TKI as well. All these drugs are available to our patients free of charge as part of a clinical trial if they fail a frontline therapy. Now if a patient fails 1, 2, 3 drugs, four drugs or more, then they can access any of the clinical trials that we have also available free of charge at MD Anderson in the third line setting, ELVN, a third generation TKI, olverembatinib versus Bosutinib, that clinical trial, Polaris that I showed you, TERN 701, TGRX 678 allosteric inhibitors are also available. And here I leave my email address. Feel free to reach out directly to me via email if you have any questions about CML, any question about clinical trials, any concern if I can help with anything. And I leave also QR codes for my social media channels where I share regularly updates regarding cancer and CML, in particular. And I want to thank you all very much for being here today and I'm very happy to go over any questions, discussions that you may have either online or offline via email. Thank you so much.

 

- Wonderful. Thank you so much Dr. Haddad. That was very thorough. And while I know that some of the tables and the details about the trials may be a little difficult to follow, I wanted to remind everyone that this video and the slides will be made available through our website after, you know, after today, probably in a week or two. And so if you wanted to revisit the video or the slides, you can do that and take some time to study it. So I also wanted to remind everyone that you can click in the Q & A box at the bottom of the zoom screen to submit any questions you have. We do have one question there and so we'll get to that in a second. We also have quite a few questions that were submitted prior to today through the registration and we'll go through some of them as well. And I just given the fact that you talked so much about new therapies and therapies that are currently in trial, I just wanted to say thank you to anybody who might be on this call who was a participant in a clinical trial because that truly is a very selfless act. It's heroic to put yourself out there and try something new for the benefit potentially of others. And I really just wanted to call that out.

 

- Maybe I would like to call that out as well. Lindsey I always say this to my patients in clinic, I truly appreciate the patients who accept or are willing to be on a clinical trial, not only for their benefit because most of the time it's for their benefit if the clinical trial is successful but also for it's for the benefits of others. And I tell them like if you were able to get Asciminib or Imatinib or Ponatinib is because 10 years ago or 20 years ago, other people like you had the selfless act of going into this clinical trial, going into all these required visits and monitoring to get the drug to where it is today. So I want to thank every patient and their caregivers for everything they do to move the science forward. Not only for them also but for the generations that are coming after them.

 

- Very good. Okay, so we have, I don't know if you want to just take a quick look at the question and answer box. There's one individual who shared a specific situation regarding side effects

 

- The question. So Cynthia - I've been on dasatinib since December 2024, so one year. So a little over a year reach MMR in June, 2025. But since then I'm remaining in minor LOD level of detection, a mild case of pleural effusion, occasional flushed face and temporary rash on the chest. Should I switch for a better and consistent MMR result? Thank you Cynthia. I think I'm going to take this question to answer it at multiple levels. Very important question. So I didn't show it for the sake of time. We had multiple studies showing that dasatinib used at the lower dose is as effective but way safer than the high dose. So if you are at 70 or at a hundred milligram, the recommendation is to lower the dose to 50 milligram per day, which will reduce the risk of pleural effusion, skin rash and other side effects. Sometimes we could even go lower to 40 or to 20. Should I switch for a better and consistent MMR? I don't think so. The survival is dictated by the fact that the BCR is below 1%, your BCR is below 1%. You you have a normal survival. Switching to another drug could expose you to more side effects and may not necessarily result in deepening of the remissions. So as long as you are in a major molecular response or a deep molecular response, I suggest you continue taking the treatment but maybe lower the dose to reduce the risk of side effects.

 

- The next one is, does every patient with CML chronic phase have a mutation?

 

- Very, very good question. We never test for the mutation frontline. So if a patient comes to us in the clinic with newly diagnosed CML, we never test for ABL1 kinase domain mutations because they don't have it. We test for other mutations such as ASXL1 and others that are associated maybe with worse outcomes. This wasn't the topic of the discussion today, but if you are talking about T315I mutation or kinase domain mutation, frontline patients or newly diagnosed patients do not have those. We never test for those. We always test them at the time of disease resistance or failure. When the patient loses the cytogenetic response. This is when we test them and we do see that every now and then.

 

- Okay, my Bosulif seems to have stopped working, I have heart failure and SOB, I'm not sure what that is. Oncologist thinks I need to change TKI, which TKI would you recommend?

 

- Yeah, so seems to stop working. I think it's a vague statement. I would like to know what are the response rate, the BCR, et cetera, how long you've been on the treatment, shortness of breath heart failure, not frequently seen with bosulif. So I would rule out other conditions before deciding that those are related to Bosulif. I'm happy to chat offline. Please feel free to email me your clinical case on my email address and I'm happy to review offline with you via email all the details and provide you accurate recommendations. Okay.

 

- Okay. And then this person's asking what is the significance of transcripts? What did they tell us about CML?

 

- So I'm not sure if that person is asking about the type of transcripts because we have two different transcript in CML, the P210, which is the very majority of the patients, more than 95% of the patients and the P190 that is in the smaller percentage of patients. They don't usually tell us much about CML except that we have more and more reports coming. Two abstracts presented at ASH 2025 in December this year showing that patients who have P190 transcript have maybe slightly higher chance of progressing to blast phase, slightly lower chances of responding. And many of them had ASXL one mutation, which we know that it is bad is associated with the lower risk of response. So I wouldn't much emphasize on it, but I keep in mind that P190 patients might somehow have kind of resistance here and there, but really this will never impact the choice of therapy.

 

- Okay. I am switching over if you see another one you want to, you want to touch on feel free, but

 

- Replied to my answer saying she's currently at 100 milligrams, I recommend that you go down to 50 milligram per day. Five zero. Okay, thank you. Alice, I have taken all the meds. Nine all nine meds. Wow. I am on Scemblix now 20 milligram Monday, Wednesday, Friday still after nine years not below 1% on BCR. My problem is low platelets. Is there anything I can do? Thank you Alice. And I'm very sorry that you're struggling with these treatments. I have few patients like this. I think this is something that we are seeing more and more these days. Thrombocytopenia related to TKI therapy. I think it's a factor of two things. Number one, some patients have a disease biology where they develop more neutropenia, anemia, thrombocytopenia with these kind of therapies. But many of them, number two is they have mutations in myeloid genes. Most frequently is ASXL1 mutation. But sometimes we do see other mutations and we know that these patients, I'm not sure Alice if you were checked for ASXL1, but these patients tend to have more cytopenias and problems. And our recommendations is if we keep struggling, I had few patients like that where I needed to do a bone marrow transplant and they are doing perfectly fine. So I think once we exhaust all treatment options, still not doing well. BCR not below 1% struggling with the treatment low counts. I think if eligible a bone marrow transplant might be the best option to do next.

 

- Sort of on that topic, there was a question that was submitted through the registration about after trying four to five TKIs, liver enzymes, thyroid, pancreas side effects. Do most CML patients have permanent damage requiring treatment?

 

- Very good question. So rarely CML patients have permanent damage requiring treatment? I think the only instances where we have seen permanent damage is the prohibitive toxicities where I put in the slide earlier and/ or the recurrent side effect that happens multiple times like pancreatitis, three, four times happening, acute pancreatitis after acute pancreatitis, it'll eventually progress to chronic pancreatitis, then it's going to be a damage. I've seen maybe one patient who has thyroid disease that was permanent, but most of the time, most of the side effects where we catch them early, we reduce the dose and eventually stop treatment and change, if not responding to dose reduction, we will end up not having permanent organ damage.

 

- Okay. There's also a question about vaccines. This individual specifically said they get red itchy spots on their upper torso when they receive vaccines, flu, DTaP or COVID and they did not get those before CML. Is that treatment related or is that related to the CML or just spontaneous?

 

- Yeah, so I don't think it's related to CML. We rarely see if ever skin rash related to CML. It is one of, it could be one of few things. It could be a side effect of the drugs. I've seen patients develop multiple skin rashes outside of the vaccine with bosutinib, with nilotinib, with ponatinib. Those are I think three most frequently involved or implicated drugs. Number two, it could be an interaction between one of the compounds of the vaccine and the CML drug. I mean there's multiple compounds in the vaccine or it could be just an allergy to the vaccine. We know that there are patients who have allergies to the vaccine. Now why it's manifesting after CML, I don't know but as long as I would say the skin rash is occurring after the vaccine is mild, it's resolving after a few days or a week with or without any treatment. So I think there's no concern to change the treatment or do anything differently.

 

- Okay. Let's see, there's one individual in the chat said they're from the Netherlands and they have a program for reducing medication. Is there research for this I think that's, what is that, like a defined period of treatment?

 

- Yeah. Thank you Jenny for this question. So there have been many clinical trials or programs, I'm not sure if you're referring to the same where we do, so patients who achieve a deep remission and maybe in a few years they are ready to stop treatment and attempt treatment discontinuation and treatment-free remission. We have two strategies. Either we tell the patient you achieve remission for many years and you stop or you achieve remission for many years, then we reduce the dose for six months one year, then we stop. So there are many program for reducing the medication with the hope of getting the patient to stop. And there are other programs like at MD Anderson we have a program now it's completed but we had a program where we did dasatinib at 50 milligram per day rather than 100. So we use a TKI at the lower dose at the reduced dose. So those programs are available in many centers across the world and I think if you have access to them, I think it's reasonable to take part of this program. I don't think these programs are harmful to patients.

 

- Okay. Here's a question about any new drugs that can be taken during pregnancy besides interferon, any lower TFR drugs or findings?

 

- Sorry, can you, can you say it again?

 

- Any new drugs that can be taken during pregnancy besides interferon? Any lower TFR drugs or findings?

 

- Yeah, so I recently wrote a review on that a month ago and if interested maybe Lindsey, I can share it with you and you can share it with the audience about pregnancy in CML. So we know that during the first trimester, most of the drugs are toxic. So I do not recommend using any of these drugs during the first trimester. We have used Hydrea in a few patients. Overall it's fine, it could lead to some growth restriction in the fetus, but if really needed we have used interferon but it's not super effective. So I think interferon and hydrea if absolutely needed in the first trimester. In the second trimester, maybe beyond gestational week 16 to 18, beyond that we can start introducing Imatinib because now we have long experience with Imatinib. We have seen some malformations, but they were similar to what we see in the general population. So beyond week 16 to 18, if really needed, again we can start doing imatinib for our patients, less likely Nilotinib. Those are the two that possibly we could use. I wouldn't use any of the others. No dasatinib, no bosutinib, no Ponatinib, no asciminib. They have been associated with malformation and side effects. Now one thing to keep in mind is if the patient is pregnant and the numbers are overall okay, even if the BCR is very high, a hundred percent, even if the white cell count is 30,000, as long as they are stable, these patients could linger for several months and they could even deliver without needing any TKI. So try to push as much as we can, but if absolutely needed Imatinib starting week 16 to 18, interferon or Hydrea before that if absolutely needed.

 

- Okay, great. Okay, we have a couple more minutes and if anybody else wants to get a last question in, please feel free to do so. And there are a couple questions here in the chat or in the Q & A, I don't know if you want to address any of those.

 

- Yes. The first one, does any patient have a mutation? We address that? Will any type of mutation, if present, show on the BCR-ABL1 test result? Very good question. It depends on the lab where you are doing the test. It depends on the sensitivity of the test that is being used. We have some tests where if the mutation is less than 5% or less than 10%, it's not detected. Some others the mutation is below that 1% is not detected. So I would ask your physician, your doctor, what is the sensitivity of the test? And if you don't have a mutation, if they are very confident that you don't have it or it's not detected, it's dependent on each lab and each test. My apologies referring to transcript that show up and the BCR-ABL1 results

 

- That was referring to the previous question about transcripts,

 

- The significant of transcripts Referring to transcript that show up in the BCR-ABL results. Yeah, these are irrelevant. We rely only on the percentage of the transcript, not on the type of the transcript. They are recently diagnosed with CML, started Imatinib BCR went from 53 to 24% after three months. Should I change the treatment? I know that the ELN guidelines say that you need to be less than 10% after three months. We know that these guidelines are very strict. I think in clinical practice I would wait until six months before deciding on the change of therapy. We know that we have a group of patients where we call them late responders, they tend to take more time than others to respond. So as long as the BCR continues to go down and it improves, I think you should continue to test at six months and try to stay on the treatment if it's benefiting you. When should a patient request mutation testing after failure of one TKI, two TKI? Very important question Lana, thanks for asking. So any failure should prompt a mutation testing, right? Like let's suppose patient is receiving first drug, they fail. And again, what is failure? Failure, again, I repeat is a BCR going above 1% or loss of a cytogenetic response. It means the karyotype that was normal, we start seeing the Philadelphia chromosome showing up again, we need to test for the mutation. If a patient responds again with a different treatment, then fails again, we retest for the mutation again. So at each failure we should retest for the mutation because it may show one time but not the other. It may be here or may not be here. So it's always important to check at each time we have resistance or failure to therapy. But not failure for side effects, failure for true disease resistance. If the BCR goes slightly up just because of side effects, we don't have to test for that.

 

- Yeah, I know that's a recommendation in other types of leukemia as well. The testing should be repeated every time there's a change in the disease, so.

 

- Okay, thank you Jenny for the stop coach for CML. Thank you.

 

- Okay, well that was great. I think we got through a lot of the questions that were submitted. All of them that were submitted during the live program and many, many from the registration. So thank you so much for that. I'm going to put our slides back up again just to acknowledge once again the sponsors of the program. I wanted to also share this page, which just has some examples of some information that you can get online. We have a lot of information specifically about testing that you might receive for your disease. Some peer support links, links to financial assistance, et cetera. Those are on our website. And then also on the right hand side, you see the NCCN patient guidelines, which I recommend to all patients and caregivers. I find them to be very thorough and a great place, especially for newly diagnosed patients to, you know, read the various recommendations and the details about the diagnosis and side effects and treatment options, et cetera.

 

And finally, I wanted to thank our speaker. Thank you so much Dr. Haddad for joining us today. I think that this was a very informative program. I also included his social media information there. If anyone can follow him to kind of keep up to date on what the information he's sharing. Any final words you wanted to share?

 

- Lindsey, thank you so very much. I'm going to send you my slides and maybe the pregnancy information so you can share with your audience. I want to thank you for coordinating and coming up with this program and I want to thank all the audience today for being here for their questions and I'm very happy to answer any remaining- I know there's a lot of questions and topics that we cannot cover in one hour, so feel free to reach out to me anytime and I'm happy to support and help continue the CML education moving forward. And thank you so very much.

 

- Thank you. Thanks everyone, and have a great day.

 

- You too. Bye-bye.

 

- Bye.