 The other category you highlighted was patients with 

 mutations. That’s a common mutation—about 25% to 30% of patients may have 

 mutations, particularly ITDs. You mentioned that we have midostaurin and the potential for quizartinib. Hetty, I’d like to ask about your approach for 

-mutated patients. Are you regularly using midostaurin in combination? Do you use it with consolidation? Do you use it for maintenance? How do you incorporate it, and how do you see quizartinib if it’s approved? It’s still an if, but let’s say—because it was a positive study—that it’s approved. How do you think you’d incorporate that and decide between that and midostaurin?

 We’re using 7+3 and midostaurin for all our patients who are FLT3 positive. We can get that information back. Regarding FLT3 status, this is for FLT3-ITD and FLT3-TKD patients. Sometimes our next-generation sequencing testing comes back after day 8 for some of the TKD mutations, but we’re typically able to start midostaurin on day 8. In the United States, we’re challenged by getting these oral medications approved by insurance companies. We’re using idarubicin, so I’ve had patients denied by insurance companies for midostaurin, because the NCCN [National Comprehensive Cancer Network] Guidelines specify that doxorubicin needs to be used rather than idarubicin. Shockingly, that has happened. Nonetheless, in the up-front setting for our patients, we’re using midostaurin during induction and consolidation and even as maintenance in the post-transplant setting, should patients be able to do that.

The quizartinib data were presented by Dr [Harry] Erba at EHA [European Hematology Association Congress] in June 2022, showing that it’s well tolerated and that patients can proceed with receiving. In that study, they received 7+3 plus quizartinib versus 7+3 plus placebo, and there was improvement in overall survival in those patients that received quizartinib. That study very much mimicked the RATIFY study, led by Rich Stone, in which patients received quizartinib day 8 through day 21, also in conjunction if they got into CR [complete response] or CRi [incomplete hematologic recovery] with their consolidation therapy with high-dose araC [cytarabine]. In that study, I believe, they had 3 years of maintenance therapy with quizartinib. What’s nice about that agent is that it’s a once-a-day dosing, and there are some advantages to that. There were some things to be mindful of with regard to grade 3 toxicities—namely, more toxicities in patients who received quizartinib vs placebo—but those were all things that are manageable. Just like in our patients receiving midostaurin, more patients came off the therapy with combination quizartinib than with placebo.

This is what we’re challenged by as we think about combination therapies in any of our patients with AML [acute myeloid leukemia], whether it’s quizartinib plus 7+3 or the other combinations we’ll talk about, including FLT3 inhibitors in combination with azacytidine-venetoclax. It’s likely that these are going to be similar. We’re eager to see some head-to-head studies regarding which 1 is better. Some of it will be tolerability, drug-drug interactions, and frequency of delivery in terms of the oral drug and what the insurance dictates vis-à-vis the United States.

I want to mention that quizartinib hits only the ITD. It doesn’t hit both ITD and TKD. That’s an important detail that we can’t forget. That’s important for us to be mindful of, especially as we roll out these targeted therapies. Finally, we also have the crenolanib study. Eunice Wang shared some of the outcomes in June 2022 at ASCO [American Society of Clinical Oncology Annual Meeting]. This study had 44 patients who went on therapy with crenolanib, a 3-times-a-day drug given with 7+3 for patients who achieve remission along with consolidation. They were allowed to receive therapy for 1 year for maintenance therapy. Many of these patients— upward of 75% to 86% of patients—were able to achieve CR/CRI. The median follow-up for those patients was 45 months, and the median overall survival had not been reached.

Interestingly, the data on the smaller subset of patients who were older showed that they were able to tolerate the therapy—

 being defined as ages 61 to 75. About 80% of patients achieved CR/CRI. That’s tolerable and good control of leukemia. There’s more to come with crenolanib, but we’ll be challenged by that with the 3-times-a-day dosing. My hope is that they’ll be able to formulate that so that it doesn’t have to be 3 times a day.

 It will be interesting to see what happens with that drug. There’s also a randomized trial going against midostaurin. [It will be interesting] to see what happens with that. You mentioned an important differentiator that I want to highlight: quizartinib is a type 2 inhibitor. It not only doesn’t hit the D835 but also becomes a mechanism of resistance to these type 2 inhibitors. The only 1 we would have would be quizartinib. Sorafenib is another, but that’s vanishing, although we used it a lot in the past. Now we have drugs approved with this indication. That’s important.

 The other thing with crenolanib is that it’s a SIK inhibitor and has some other attributes. When you think about resistance, that’s something to keep an eye on.

 Absolutely. Before I move to the next category and subset of patients, I want to ask Brian about the quizartinib and the midostaurin studies. Both are positive and statistically significant. There’s a clear advantage in survival, but the benefit is modest. Are you disappointed? Is that what you expected? How do we move from here?

 As you pointed out earlier, outcomes for patients with AML have improved steadily over time. Perhaps I’ll take any benefit and be happy with it. Could the benefits be greater? Absolutely. That’s always been a criticism of midostaurin. With the more potent drugs, which are still being evaluated in randomized fashion, like gilteritinib and crenolanib, perhaps there will be more signal there than with the quizartinib and midostaurin. I like the way those studies are set up, as randomized trials with midostaurin being the control arm. I’m moving slightly away from your question, but I want to get the point in that we still aren’t sure whether a broad kinase inhibitor—with multiple targets up front—might be a rational way to treat AML. As we all know, it’s a malignant clonal. In many cases, or the more potent, more selective inhibitor might be better up front in terms of having general effect and able to prevent relapse. Going back to the original answer, I’m happy to see any benefit whatsoever when I take care of patients with AML. I’m hopeful that some of the more advanced TKI[tyrosine kinase inhibitor] will prove more exciting once those phase 3 studies read out.

 I’m with you. We’re not going to see an interferon ... dramatic change. This is AML; it’s a lot more complex. I’ll take this benefit. Would I like more? Sure, but this is AML.

Videos

Expert perspectives on the emergence of FLT3-targeted therapies and their role in the first-line setting of acute myeloid leukemia management.

Frontline Therapy for Patients With AML and FLT3 Alterations 

 Let’s move on to treatment. We’re going to start by addressing frontline treatment. We started talking about this issue of fitness, but I’d like to ask Margie about how we address the therapy. We talked about this intensive chemotherapy, and I’ve always thought that 7+3 was like a wimpy treatment, but it’s been around since the 1970s. Is that still the standard for the standard-risk patient. Are there deviations in some settings that you prefer to use? Focusing on the chemotherapy itself, are there areas where you focus differently for these patients?

 First, I agree about 7+3. I don’t know about wimpy, but I’d be happy to see it fade off in the distance as we better understand what we could be doing for our patients. In terms of fit patients, we’re still focusing on cytogenetic and molecular markers to push us forward into what we’re going to do. Favorable-risk cytogenetic patients—core-binding factor patients, for example—are still using the 7+3 backbone with the addition of gemtuzumab ozogamicin because there are good data to support that those patients can move forward in chemotherapy-only path toward cure. At our institution [Thomas Jefferson University], that’s our standard for fit patients with favorable-risk cytogenetic disease.

For the remainder of the patients, the question is what other markers might they have? For 

-mutated patients, we’re adding FLT3 inhibitors to their standard, 7+3. There’s only 1 approved combination, which is midostaurin plus that combination of chemotherapy. But we have an [expected] FDA approval date [April 23, 2023] for quizartinib in combination with 7+3; that’s coming soon. We have a trial that has ended accrual, and it’s going to be a bit until we know the answer. [This study] looked at gilteritinib vs midostaurin in this up-front 7+3 setting.

Then there’s a whole slew of FLT3 inhibitors plus other bases like Vyxeos [daunorubicin, cytarabine], which is the liposomal version, essentially of 7+3; the data for that is also coming. For that group of patients, we still have that intensive chemotherapy with the inhibitor. The patients we pulled out of using aggressive chemotherapy are 

-mutated patients. Biology, in terms of fitness for the patient, isn’t something we’re considering in our institution because 7+3 isn’t valuable in that patient population.

Clinical trial is a top 3 choice if we can do it. If not, then there are some data with other combinations like FLAG-IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin]–venetoclax, which might be better than 7+3 in that patient population. Intermediate-risk [patients] have almost disappeared now that we have a better understanding of molecular abnormalities. That’s the group that I probably would have said got 7+3 most. Now they’re pushed into the adverse and better-risk categories. I don’t know if other people on the panel have thoughts in addition to that.

That’s a great overview. Before I turn to the others—we’ll go through all the categories you described because they all have unique features on how we address the treatment—I want to get back to the core binding factors. You mentioned gemtuzumab. Do you do it routinely in all your patients? Do you include gemtuzumab in the treatment? Do you use it with 7+3? At the MRC [Medical Research Council], they use it with FLAG [fludarabine, cytarabine, granulocyte colony-stimulating factor], which is more intensive. What’s your consolidation on these patients? For these patients, we don’t typically transplant as an initial attempt for the cure. How do you consolidate these patients?

 We’re using 7+3. One reason…for that combination was that there’s a practical issue with fludarabine shortage. In our institution, we’re keeping our fludarabine for transplant patients or for patients who we feel need to get things like FLAG-IDA [fludarabine, cytarabine, granulocyte colony-stimulating factor, idarubicin], as opposed to where we feel that we have an appropriate combination chemotherapy for these patients. From a practical issue, we have that. We consolidate with high-dose cytarabine and gemtuzumab, which is not the same as with the study, where they got it only for the first 2 cycles and then 4 cycles total of high-dose cytarabine. There are challenges with this. Even young and very healthy patients, in my experience, have higher infection rates and more issues with platelet recovery than when we don’t use it. But the outcomes are excellent. That’s what we’re standardly giving to our patients.

Centering focus on first-line treatment modalities, panelists highlight the ongoing role of intensive chemotherapy in the management of AML.

Role of Intensive Chemotherapy in Young, Fit Patients With AML

 We’ve discussed the molecular classification, but another important classification that we must also consider is the one that we increasingly talk about, whether the patient is fit or unfit for therapy because that also has important implications as to how we manage a patient. I’d like to ask Hetty, how do you define the fitness? Is it age? Is it comorbidities? Do you use one of these scores that have been developed? How do you assess that fitness?

 I don’t personally use a scoring system for our patients, although that is perfectly acceptable if people are using that, and certainly, for patients that are headed to transplant, they use a score to evaluate for comorbidities. I will argue that for some of our patients that begin therapy for AML [acute myeloid leukemia], they can become unfit because of the AML and how long they’ve had and been suffering from the toxicities of leukemia itself. We are often challenged with getting the results of next-generation sequencing. If a patient’s disease and tempo of disease is such that they’re in the ICU, hypotensive, have many issues with a pneumonia or some other type of sepsis, and/or involvement of the parenchyma or other types of skin involvement, for some of those patients, I move quickly and use induction chemotherapy. I don’t often wait for next-generation sequencing or chromosome tests to come back, especially in our patients that are younger and otherwise fit with very limited comorbidities. Many of our patients with this diagnosis are over the age of 65, and it’s unusual to have patients that have no other comorbidities, but it can be that those comorbidities are well managed or well controlled. For some of those patients, we can move forward with induction chemotherapy and we often can offer those in the upfront setting, especially if we have a clinical trial that they are eligible for, and in that clinical trial, it allows for the addition of newer novel agents to help with the improvement of what we expect to be the standard outcome. The same is true for patients that may be moving forward with other regimens, such as azacitidine [Vidaza]and venetoclax [Venclexta], where we have many clinical trials that use those 2 agents and offer a novel therapy. With regard to fit or unfit, we are equally filling in those classifications based on our clinical trial paradigms. For the clinical trials, they often want us to quantify or meet certain ECOG [Eastern Cooperative Oncology Group] performance status criteria to move forward on study or not. The biggest pieces to this for my patients are listening to how they were doing before they were diagnosed or having symptoms of AML. Even if they’re not fit at the current time, if you start them on therapy and reassess after the first cycle of disease, they can get better once their leukemia is better controlled. Those are things that are hard to quantify in a scoring system, and one of the reasons why we remain challenged by the definition of fit or unfit because I believe it’s dynamic more than static.

 I agree, and as somebody who’s already up there in age, I think that we need to remember that it’s not just an age factor. There’s certainly older patients who can be very fit for more intensive chemotherapy, and there are younger patients that because of other reasons, they cannot handle it. I’m glad you brought up the issue that this should be a dynamic assessment of the patient because that can evolve. You don’t just classify them at the time of diagnosis and stay with that. They can go from unfit to fit or vice versa, and you must adjust to that and provide the best treatment for the patient.

Expert oncologists reflect on risk stratification in acute myeloid leukemia and the process of categorizing patients into ‘fit’ versus ‘unfit’ subsets.

Acute Myeloid Leukemia: Optimizing Risk Stratification

 That’s very important. That’s part of our understanding about the disease, and that’s what’s made all these sub-classifications. One of the challenges that we all face with this molecular characterization and with the cytogenetic characterization, because some of these are still based on the cytogenetics, is that it takes time. Dr Carraway was alluding that the problem is that these results in some academic institutions, we can get some of them a little sooner, but in general, in practice, they take a while. Dr Jonas, how do you manage that timing, from the time you get your patient and having to wait, do you start? Do you wait? How do you manage that?

 Thanks for that question. I agree with everything that’s been said thus far, and 2022 to me, has been a watershed year in terms of when we think about what AML [acute myeloid leukemia] is and how do we deal with it at the very beginning of a patient’s journey. This question gets to that story a little bit. There’s several lines of evidence to suggest now that you can wait to start treatment without affecting a patient’s overall prognosis. We showed that using a California discharge dataset, and it was shown in a large European study as well, but then again, the trouble with such data is these are population statistics. You’re sitting in the room with a patient who has AML, and you need to make that decision about whether they can wait. There’s several factors that go into that, and we were all raised with the idea that AML is a medical emergency, you must treat it right away or something bad will happen. There certainly are patients like that where their white count is very high, and they may have leukostasis or other complications from the high white count, and you may be forced into doing treatment quickly. There are many patients on the other hand that present with a more stable disease and more stable clinical situations, and many centers will even discharge these patients with close follow-up in the outpatient setting and allow the time that’s required for these advanced cytogenetic and molecular panels to come back so you can offer a patient optimal therapy in 2022, almost 2023 now. That’s important, but not everyone has such resources. There’s going to be situations where that’s not feasible, where patients may have come from far away and it’s not easy for them to get back to a local area. And this can put a strain on the hospital resources, to have a patient sitting in the hospital for a week waiting for things to come back. This puts the impetus on us at the field to develop better rapid readout assays and have short turnaround times that include the relevant mutations, and then you can wait for the more prognostic mutations to come back later. When you think about mutations, IDH or FLT3, and other things that might be acted upon early on having tests where those turn around rapidly and having such tests available, not just in academic centers, but to the community, I think will really help steward resources appropriately. Ultimately, there’s a lot of fear out there with the disease and the data are reassuring that we can get away with waiting in some patients. I also point out there is an increasing use of a practice of giving patients a little bit of temporizing therapy to them in these high-risk situations to wait necessarily for the start of their definitive therapy. That’s another approach that you see used more.

In light of novel targeted agents made available to patients with AML, panelists consider the value of timely molecular testing in this setting.

Molecular Biomarker Testing in Acute Myeloid Leukemia

 I’d like to ask Dr Kasner, in this classification, what are the subsets that you think were in attention because they’re more frequent, or they’re more challenging? Which ones would you highlight as the ones to pay the most attention? Of course, they’re all important, but which ones do you find particularly challenging or common?

 I think we need to step back a second because you mentioned FAB [French-American-British classification], which was how we classified a long time ago, and since then, the WHO, World Health Organization, has led our classification systems. This year we have a unique challenge, which is that we now have 2 classification systems. In addition to the fifth WHO classification system, we also have the International Classification Consensus, or ICC. Talking for a moment about their similarities and differences leads to where we should focus because I think the goal of these is to help us focus. One of the things that’s interesting is that the ICC merged all the AMLs [acute myeloid leukemias] defined by the differentiation markers, which is what you were talking about, the sort of M0 all the way through M7, into an AML, NOS category. But that’s not that important. You don’t need to focus on that. What you need to focus on is defined cytogenetic abnormalities. Those are things like what defines acute promyelocytic leukemia, which is the PML-RARA fusion and the long list of the core-binding factors and other genetic abnormalities that are well defined. The ICC said that some of them are so important that you only need 10% blasts if you have one of these translocations to be called AML. It’s AML. Now, both maintained 20% blasts for other settings, including AML with the BCR-ABL translocation, which used to think of as some form of CML [chronic myeloid leukemia], but now can be called AML. [It] then became an expanded classification of AML with myelodysplastic-related changes, which no longer focused on morphology, but on MDS [myelodysplastic syndromes]-related gene mutations. This is an important place for us to focus in terms of subtypes. I don’t need to read the list to you, but the important thing is that the ICC and the WHO agree on everyone except for [INAUDIBLE]. They’re saying to us, pay attention. These are important, and honestly, generally poor prognostic indicators for our patients, and we must pay attention to these things. The other thing that they said was that prior cytotoxic therapy is now a qualifier, but not a subtype. Why is this important? Because we’ve always known that if you had chemotherapy from breast cancer, but you got a core-binding factor leukemia, that the biology was most important, not that you had had previous chemotherapy. Again, they’re saying to us, the biology is what’s important. These abnormalities, FLT3, the most common for a prognosis abnormality that we see in our clinics. I think that the new classification systems are pushing us to look at what is important, which is the molecular abnormalities and the biology of the disease, and much less about what we used to classically think of as sub-categorizations by things like morphology.

Expert perspectives on current classification strategies in acute myeloid leukemia and how these guidelines make use of molecular markers.

Current Classifications of Acute Myeloid Leukemia  

titled, “Expert Perspectives on Current and Emerging Therapies for AML.” My name is Jorge Cortes. I’m the director of the Georgia Cancer Center at Augusta University in Augusta, Georgia. I’m joined today by a panel of experts in AML [acute myeloid leukemia]. I would like to welcome all my esteemed fellow panelist and I would like to ask them to introduce themselves. I will start with Dr Carraway, please.

 Hi, everybody. My name is Dr Hetty Carraway. I’m the leukemia director at Cleveland Clinic in Cleveland, Ohio, and I’m delighted to be here and excited for our discussion.

 Hi, I’m Dr Margie Kasner. I am the leukemia director at Thomas Jefferson in Philadelphia, and I’m looking forward to today.

 I’m Dr Brian Jonas. I’m at UC Davis, California, and I lead our leukemia program, both clinical and research.

 Thank you, and welcome everyone. Thank you again for joining us in this program. Today we’re going to discuss several recent updates in the treatment of acute myeloid leukemia with a focus on what has been presented at key conferences in this year 2022. We will discuss the data and put it in the context of the guidelines and the treatment landscape, and our own clinical practice and how it impacts some of what we’ve been doing so far. First, we’re going to do a quick overview of acute myeloid leukemia. Acute myeloid leukemias represent a relatively small percentage of all cancers; it’s about 1% of all cancers in the United States. It is estimated that in 2022, approximately 20,000 individuals will be diagnosed with acute leukemia. And there’ll be approximately 11,000 to 11,500 deaths from acute myeloid leukemia in 2022; that represents about 1.9% of all cancer-related deaths. The relative incidents of AML have not changed much over the years but the relative survival has somewhat improved over the years. Right now, the estimated 5-year relative survival is about 30%. There is not much of a difference in the relative survival or in the relative mortality. Over the years, the incidents and survival are both somewhat higher in men than in women, and there is some difference in the survival rate according to different races, and that’s an important topic that has led to much discussion in access to clinical care. But we don’t have much time to address that at this moment. One important recent change has been the awareness of the molecular complexity of acute myeloid leukemia. When we talk about acute myeloid leukemia nowadays, we’re no longer talking about 1 disease, but many diseases. We’ve evolved from the old FAB [French-American-British] classification that some of us are old enough to remember from M1 to M7, eventually we added M0. We no longer use that classification, but we are talking more about the cytogenetics and the molecular complexities. I’d like to ask our panel, how have you incorporated that molecular classification and that cytogenetic, and put it all together into your practice today? First, Dr Carraway, how are you doing this in your practice? How do you incorporate this into your treatment algorithms?

 When we think about our patients with AML, the standard approach to our patients and their workup includes evaluating their complete blood count and obtaining a bone marrow biopsy with aspirate, and that aspirate helps us to collect information such as flow cytometry and chromosome analysis, as well as next-generation sequencing. It is a central part of setting up a patient’s next steps in terms of their therapy. For example, the results from the next-generation sequencing can inform and help us understand the risk profile that a patient may have. We are often challenged by waiting for some of those results, but in our patients that are older and have white count that’s in an unmanageable state, we can wait for the information for comprehensive cytogenetics, the FISH [fluorescence in situ hybridization] testing, as well as the next-generation sequencing. This can help us profile patients as to whether they’re in a favorable-risk category, or an intermediate-risk category/adverse-risk category. This is important because we need to have these conversations with our patients and their loved ones, regarding the likelihood of benefit of intensive therapy and the outcomes that they should expect with the treatments moving forward. It’s important to have these discussions with patients because as you alluded to and reviewed, the outcomes for our patients, although they’re somewhat better than in years past, still aren’t what we hope they should be. I imagine that Dr Kasner will be able to highlight some of that, especially with our expertise in the older patient population where we must have these conversations with them. If we have patients that have a core-binding factor cytogenetic abnormality, we are hopeful that they’re sensitive to cytarabine-based therapy. We have novel therapies with targeted agents that we’ll be talking about today, and we also have agents, such as venetoclax [Venclexta] in combination with azacitidine [Vidaza], that we’ll be walking through. Some of the challenges in our older patient population include the fact that many of the leukemias are not de novo, but rather a secondary or an emerging AML from an underlying antecedent hematologic malignancy. For those patients, we worry that their outcomes will not be enduring with a chemotherapy-only based approach, and we must balance that with the morbidity and mortality of transplants. I’m eagerly interested in the comments from our colleagues today and what thoughts the group has today to talk about.

Opening their discussion on the management of acute myeloid leukemia (AML), expert oncologists provide an overview on the incidence, diagnosis, and stratification of patients. 

Overview of Acute Myeloid Leukemia 

Hetty Carraway, MD, associate professor of Medicine, the Cleveland Clinic Lerner College of Medicine of Case Western Reserve University, and member, Hematology and Medical Oncology, the Cleveland Clinic, discusses the role of biomarker testing in patients with myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). 

Identifying relevant genomic information has helped shape treatment options for patients with myeloid malignancies, AML, or MDS, Carraway says. This information has helped physicians better classify a disease’s underlying biology and its drivers to the leukemogenesis and pathogenesis, Carraway explains. The speed of these tests has also improved, allowing for faster identification of the best therapy plan for each patient, Carraway adds.

Oncologists continue to ask if mutations can help to identify resistance pathways to specific drugs, and this has shaped frontline treatment choices, Carraway continues. These tools help evaluate minimal residual disease, plus optimal therapy at diagnosis and during remission, Carraway concludes.

Hetty Carraway, MD, discusses the role of biomarker testing in patients with myelodysplastic syndromes and acute myeloid leukemia. 


Dr. Carraway on the Importance of Testing for Biomarkers in Patients with MDS and AML

Hetty Carraway, MD, associate professor of medicine, Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, vice chair, Strategy and Enterprise Development, Taussig Cancer Institute, Cleveland Clinic, discusses important considerations for the future of acute myeloid leukemia (AML) regarding mutations and next-generation sequencing.

Mutations in AML are crucial markers of patient prognoses, Carraway says. Sequencing at the time of diagnosis, as well as throughout therapy, can reveal which mutations may be most sensitive to certain therapies, Carraway continues.

Sequencing should not be a static event but rather a way to receive data about refractory and responsive patients and gain more knowledge of resistance pathways, Carraway notes. Thinking about measurable residual disease is an important step toward determining additional treatment options for many patients with AML, Carraway concludes.

Sponsored in part by Servier Pharmaceuticals. Content independently developed by OncLive.

Hetty Carraway, MD, discusses important considerations for the future of acute myeloid leukemia regarding mutations and next-generation sequencing.

Dr. Carraway on Next-Generation Sequencing in AML

Hetty Carraway, MD, oncologist, Cleveland Clinic, discusses predisposition to acute myeloid leukemia (AML).

Research has been done on the presence of mutations in patients who do not possess a hematologic malignancy. This research led to understanding of the presence of mutations and clonal hematopoiesis of indeterminate potential. That work was seminal in leading other research groups to question the development of AML in larger cohorts of patients, says Carrway.

In that research, as many as 150,000 patients who had leukemia were selected. These patients were retrospectively examined via serial samples of blood as far as 10 years prior to their diagnosis to see what happened following the detection of mutations. In that time span, researchers were able to identify differences in the presence of mutations and the variant allele frequency in specific genes that were associated with a higher risk of progression to AML compared to those who did not have those mutations, states Carrway. That work has enabled physicians to think more deeply about changing that trajectory for patients, adds Carrway.

Hetty Carraway, MD

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