The panelists, Gail J. Roboz, Jorge Sierra, and Jorge Cortes, shared their perspectives on treatment decisions for patients with FLT3-mutated acute myeloid leukemia, including choice of FLT3 inhibitor, how FLT3-mutated measurable residual disease (MRD) might guide transplant decisions, as well as the importance of monitoring FLT3-mutated MRD with the appropriate assay. 

This educational resource is independently supported by Daiichi Sankyo. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

Roboz reflected on whether 7+3 regimens are the most appropriate approach for older patients with FLT3-mutated AML, and reviewed considerations for using targeted FLT3 inhibitor therapies in combination with standard intensive chemotherapy. She then highlighted the importance of measurable residual disease (MRD) assessment in guiding treatment decisions before and after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and the potential of triplet therapies for the treatment of patients with FLT3m AML.

This educational resource is independently supported by Daiichi Sankyo. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

Cortes describes the mechanisms of action of Type I and Type II FLT3 inhibitors, followed by an overview of key efficacy and survival data from clinical trials of FLT3-targeted therapies.

This educational resource is independently supported by Daiichi Sankyo. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

Sierra provided an overview of the role of FLT3-internal tandem duplication (ITD) and -tyrosine kinase domain (TKD) mutations in AML pathogenesis, and the differences in their molecular characteristics. He then discussed the prognostic value of FLT3-ITD and -TKD and concomitant mutations in patients with AML, and current risk stratification guidelines.

This educational resource is independently supported by Daiichi Sankyo. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

In this interview, Roboz discusses key findings from a preliminary subgroup analysis of a phase Ib/II trial (NCT04086264), investigating the anti-CD123 antibody–drug conjugate pivekimab sunirine in combination with azacitidine and venetoclax, for ≥14 days or 28 days, in unfit patients with newly diagnosed CD123-positive AML. The primary endpoint was antileukemic activity, including complete remission (CR) and composite CR with incomplete hematologic recovery (CR/CRi) rates.

This educational resource is independently supported by AbbVie. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

In this interview, Fathi discussed key findings from the open-label, randomized, phase II PARADIGM trial comparing azacitidine + venetoclax with conventional induction chemotherapy in functionally fit patients with newly diagnosed AML (NCT04801797). The primary endpoint was event-free survival.

This educational resource is independently supported by AbbVie. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

Stein starts by discussing therapies approved for the treatment of IDH1-mutated (IDH1m) AML, including ivosidenib and olutasidenib, and supporting data. He then considers strategies in development for IDH-mutated AML, such as combining IDH1 inhibitors with venetoclax, before concluding with areas of interest for future research. Stein talks about the potential of IDH1 inhibitors in precursor states of myeloid malignancies, such as clonal cytopenia of undetermined significance (CCUS), and the aims of ongoing studies.

This educational resource is independently supported by Servier. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

Searle summarizes the key considerations when using menin inhibitors in the treatment of NPM1-mutated (NPM1m) or KMT2A-rearranged (KMT2Ar) acute myeloid leukemia (AML) in clinical practice, and her thoughts on key areas of interest looking forward.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

Hosted on Acast. See acast.com/privacy for more information.

This educational resource is independently supported by Johnson & Johnson. All content was developed by SES in collaboration with an expert steering committee. Funders were allowed no influence on the content of this resource.

Hosted on Acast. See acast.com/privacy for more information.

This independent educational activity is supported by Thermo Fisher Scientific. All content was developed independently by the faculty. The funder was allowed no influence on the content.

Hosted on Acast. See acast.com/privacy for more information.

Know AML hosted a webinar for patients and healthcare professionals (HCPs) on April 23, 2025, titled ‘Mutation testing in AML: What you need to know’. Here, we share a discussion between Gail J. Roboz, Weill Cornell Medicine, New York, US, and Ralph Hills, Connecticut, US, where they consider how physicians and patients can communicate more clearly about mutation testing in AML.

Roboz emphasized the importance of providing patients with clear, evidence-based information in a supportive manner, avoiding overwhelming technical language unless requested. She highlighted the need for open communication, encouraging questions, and creating a space where patients feel comfortable and empowered to make decisions. Hills enquired about the application of artificial intelligence (AI) in guiding treatment. Roboz explained that though online tools such as Google and AI may seem helpful, they can often mislead, and put forward that, regardless of how much information patients have, patients want to feel genuinely cared for and to know someone is looking out for them, while Craddock noted that AI could be useful in streamlining clinical trials and improving their accessibility for patients. Roboz identified the value of staying informed about the latest treatments, especially for serious conditions such as AML, and encouraged patients to ask critical questions about their disease, diagnosis, and treatment plan. Craddock added that collaboration among physicians is also crucial to ensure patients receive the best possible care.

Hosted on Acast. See acast.com/privacy for more information.

They went on to debate challenges faced by patients during an AML diagnosis, including access to mutation testing and discussions between physicians and patients. They concluded by describing the importance of shared decision-making, and the role of physicians and patients in enabling clearer conversations about mutation testing in AML going forward.

Key points

• The estimated number of new cases of AML in the US in 2024 was 20,800 – 1% of all new cancer cases in the US. Survival rates have improved steadily over the past 50 years.
• Since 2017, many drugs designed to target specific mutations have been approved by the U.S. Food and Drug Administration (FDA) and the European Union (EU).
• Patients face several challenges during the process of being diagnosed with AML, including lack of awareness of testing methods, the wait time for test results , and accessing appropriate testing methods; therefore, clear communication between physicians and patients is essential.
• Several mutation testing methods are available, including conventional cytogenetics (karyotyping), fluorescence in situ hybridization (FISH), polymerase chain reaction (PCR), and next-generation sequencing (NGS), and these techniques continue to evolve.
• Physicians play a vital role in guiding patients towards appropriate diagnostic tests needed to inform treatment decisions. Providing access to testing methods, whether as part of diagnosis and monitoring in clinics or through clinical trials, is important. For example, the US myeloMATCH trial uses NGS mutation testing to assign patients to treatments that target their specific mutations and then tests how well and safely these treatments work.
• Shared decision-making between physicians and patients is crucial to set realistic expectations for treatment and recovery, improve results following treatments, and help patients to feel more confident, independent, and in control of their health.

This independent educational activity is supported by Thermo Fisher Scientific. All content is developed independently by the faculty. The funder is allowed no influence on the content.

Hosted on Acast. See acast.com/privacy for more information.

This independent educational activity is supported by Thermo Fisher Scientific. All content is developed independently by the faculty. The funder is allowed no influence on the content.

Hosted on Acast. See acast.com/privacy for more information.

This educational resource is independently supported by Bristol Myers Squibb. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource. 

Hosted on Acast. See acast.com/privacy for more information.

Hosted on Acast. See acast.com/privacy for more information.

In this interview, Roboz walks through the changes in the classification criteria for AML over the last 50 years, highlighting the implications of these changes and the lack of consensus on the diagnosis and management strategies for patients. Roboz goes on to discuss both classification and prognostic risk stratification tools to aid in the development of management strategies, including in HR AML, and concludes by highlighting the importance of considering patient preferences and health when making clinical decisions.

This educational resource is independently supported by Jazz Pharmaceuticals. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource. 

Hosted on Acast. See acast.com/privacy for more information.

Hosted on Acast. See acast.com/privacy for more information.

Hosted on Acast. See acast.com/privacy for more information.

Hosted on Acast. See acast.com/privacy for more information.

Firstly, Roboz and Daver discuss the impact of blast count on the diagnosis of AML and how a patient's mutational profile can affect treatment decisions. They highlight available, effective lower-intensity and targeted therapies and a potential transition to a fully genomic- and cytogenetic-based classification of AML. Finally, they discuss current patient selection strategies for intensive induction chemotherapy and future directions in AML treatment.

Hosted on Acast. See acast.com/privacy for more information.

Gavriilaki begins by discussing a study presented at EBMT 2022 that explored outcomes of fludarabine + treosulfan, which followed on from previous studies exploring treosulfan. Gavriilaki details the study design and patient population, explaining which comparative therapies were used and why. Finally, Gavriilaki outlines different studies presented at EBMT covering fludarabine combinations for patients with AML and MDS.

Hosted on Acast. See acast.com/privacy for more information.

Nagler begins by discussing the importance of MRD in AML treatment and transplantation. He highlights the significance of MRD in different settings as a prognosis factor and describes the result of his study presented at EHA2021. Finally, he outlines the current treatment landscape for transplants in relation to MRD status and makes recommendations for MRD-positive patients.

Hosted on Acast. See acast.com/privacy for more information.

Craddock begins by outlining the reasons for the increased use of allogeneic transplant and reviews data that discuss the exclusion criteria and benefits of transplant. He goes on to discuss how patient outcomes could be improved and the importance of post-transplant maintenance. Finally, he highlights the need to generate prospective data, referring to the ongoing studies COSI and AMADEUS.

Hosted on Acast. See acast.com/privacy for more information.

Ossenkoppele begins by outlining emerging techniques in MRD, such as next-generation sequencing. He goes on to describe how risk category and MRD status can inform treatment decisions, such as for allogeneic stem cell transplant.

Hosted on Acast. See acast.com/privacy for more information.

Ravandi begins by highlighting the limited maintenance approaches for patients with AML. He continues with the promising results from the QUAZAR AML-001 study evaluating oral azacitidine (CC-486), an oral hypomethylating agent, which can be used for maintenance and to improve eligibility for hematopoietic stem cell transplantation.

Hosted on Acast. See acast.com/privacy for more information.

Wei starts by introducing the clinical study data from AMLM16, a randomized, placebo-controlled trial evaluating sorafenib versus placebo in combination with intensive chemotherapy for previously untreated adult patients with FLT3-ITD AML. In this study, sorafenib did not improve event-free survival when combined with intensive chemotherapy; Wei discusses the possible causes of this result and the subgroups that did better in the sorafenib arm. Anstee then reports the results from the correlative studies evaluating the impact of sorafenib on phospho-FLT3 inhibition and the presence of FLT3-ITD measurable residual disease after chemotherapy.

Hosted on Acast. See acast.com/privacy for more information.

Clinical studies evaluating the combination of venetoclax + azacitidine versus azacitidine alone have shown that patients with AML with IDH1/2 mutations treated with venetoclax + azacitidine achieved higher response rates, and had better outcomes, compared with patients treated with azacitidine alone.

In this podcast, Pollyea discusses the results of a study further evaluating the efficacy and safety of venetoclax + azacitidine in treatment-naïve patients with AML with IDH1/2 mutations unfit for intensive treatment. Data were combined from two different studies: a phase Ib study where patients were treated with venetoclax + azacitidine and the VIALE-A study (NCT02993523) comparing patients treated with venetoclax + azacitidine versus placebo + azacitidine.

Hosted on Acast. See acast.com/privacy for more information.

Emerging data on venetoclax combinations in patients with FLT3-mutated AML have been presented at ASH 2020. FLT3 mutations are the most common mutations in patients with AML.

In this podcast, Daver discusses the results of a study comparing the combination of azacitidine plus venetoclax versus azacitidine plus placebo in patients with FLT3-mutated AML. He also talks about a study evaluating the combination of gilteritinib with venetoclax in patients with relapsed/refractory FLT3-mutated AML and reports the results of the first combination of decitabine + venetoclax + FLT3 inhibitor of clinician’s choice in patients with FLT3-mutated AML.

Hosted on Acast. See acast.com/privacy for more information.

In this podcast, DiNardo gives an overview of the studies on venetoclax combinations presented at ASH 2020, especially venetoclax plus azacitidine, in mutation subtypes of AML.

DiNardo focuses on three specific subgroups: patients with IDH1/2 mutations; patients with FLT3 mutations; and patients with TP53 mutations. After talking about the promising results reported at ASH, DiNardo pointed out that unmet needs still exist, especially for patients with TP53 mutations.

Hosted on Acast. See acast.com/privacy for more information.

Jorge Sierra describes the clinical benefit of adding drugs that target mutations into treatment regimens and explains the importance of mutational profiling at diagnosis and relapse to determine treatment options. He discusses target therapies that are available to patients, including the following:

• midostaurin (FLT3 inhibitor) for the frontline setting
• ivosidenib (IDH1 inhibitor) for the relapsed/refractory (R/R) setting
• enasidenib (IDH2 inhibitor) for the R/R setting
• gilteritinib (FLT3 inhibitor) for the R/R setting

He concludes by discussing other novel agents that have shown efficacy in the treatment of AML, including venetoclax and gemtuzumab ozogamicin.

Hosted on Acast. See acast.com/privacy for more information.

Identification of disease-driving genetic aberrations has allowed for major advancements in the AML setting. TP53 mutations are observed in around 15% of patients with AML, with distinct patterns between patient subsets. Despite the development of targeted therapies, such as FLT3 and IDH1/2 inhibitors, treatments targeting TP53 mutations are yet to be established.

TP53-mutant AML is an area of unmet need, demonstrating high interpatient heterogeneity. Here, Naval Daver describes the efforts being made to establish TP53 as a therapeutic target, with the aim to further improve patient outcomes.

Hosted on Acast. See acast.com/privacy for more information.

In this podcast, Dr Davar starts by providing a background on the importance of the microbiome in adaptive and innate immunity, while Dr Spencer states the importance of the cross-talk between the microbiome and immune system through microbial products, peptides, and metabolites. Dr Davar then explains the concept of immunosurveillance, immunoediting, and checkpoint inhibitors. Dr Spencer describes fecal microbiome transplant studies that showed features of the microbiome can predict response to immunotherapy and effect T-cell expression. Dr Davar then describes some of the studies that are looking at fecal microbiome transplant in combination with checkpoint inhibitors. He goes on to discuss studies investigating the use of live bacterial products to elicit the same effects as fecal microbiome transplant, particularly the mediation of CD8 T cells. Dr Spencer also talks about probiotics, antibiotics, and diet and explains how this can affect the gut microbiome and describes studies looking at these features in terms of response to immunotherapies. She also describes the microbiome research related to graft-versus-host-disease and the impact of higher alpha diversity on post-transplant survival, while Dr Davar explains how the microbiome may also affect toxicity and side-effects of cancer immunotherapies. 

Hosted on Acast. See acast.com/privacy for more information.

The question was, Is CD47-directed antibody therapy safe and effective in patients with AML and myelodysplastic syndromes?

CD47 is a dominant negative immune checkpoint expressed by cancer cells, which facilitates immune evasion by decreasing recognition by macrophages. Increased expression of CD47 on cancer cells has been associated with inferior survival in patients with AML. The first-in-class anti-CD47 antibody magrolimab reinstates macrophage-mediated phagocytosis of tumor cells and has demonstrated anti-tumor activity in preclinical models.

Here, David Sallman and Naval Daver discuss the potential and clinical status of CD47-directed antibody therapy for the treatment of AML and myelodysplastic syndromes.

Hosted on Acast. See acast.com/privacy for more information.

The group start by discussing the problems clinicians face when deciding treatment plans for patients with secondary myeloid neoplasms and describe how exposure to prior DNA damaging agents, cytotoxic therapies, and genotoxic therapies, can lead to a complex karyotype in these patients.

The group then discuss the role of clonal hematopoiesis in the evolution of secondary myeloid neoplasms. Dr Saygin describes how this could be a possibility especially for TP53 mutated, therapy-related AML, he also provides another hypothesis that genotoxic agents could cause de novo mutations. The group also discuss other driving mutations for clonal hematopoiesis including MPN1, SRSF2, and ASXL1, before moving on to discuss how specific genotoxic therapies can generate specific mutations. Dr Saygin and Dr Ozga describe their study in which they analyzed the molecular footprint of patients who had received various genotoxic and cytotoxic agents in order to answer this. Dr Singh also discusses his data on how the development of novel agents, such as immunotherapies may actually reduce the risk of secondary myeloid neoplasms compared to previous treatment options.

The discussion ends on the note that these types of studies will eventuality allow clinicians to predict disease risk better and provide more suitable therapies based on the patient's particular molecular profile.

Hosted on Acast. See acast.com/privacy for more information.