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Mutation testing in AML:
What you need to know
with Charles Craddock, Ralph Hills, and Gail Roboz
Wednesday, April 23, 2025
17:30-18:30 BST
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The “How I Treat” series, featured in Blood, highlights expert perspectives on the diagnosis and treatment of patients using sample patient cases, and the AML Hub has previously covered topics in these series on the use of new therapeutics and updated classification systems. Although there have been some major advancements in the treatment of patients with acute myeloid leukemia (AML) in recent years, relapsed/refractory (R/R) AML is still associated with poor outcomes.1
Here, we summarize key points from a recent “How I Treat” article by Thor et al.,1 discussing the treatment of patients with R/R AML, in three patient cases.
The 2022 European LeukemiaNet (ELN) recommendations include response criteria for R/R AML, incorporating both hematologic measures and the assessment of measurable residual disease (MRD). Molecular reevaluation should be carried out when diagnosing a patient with R/R AML as this may influence treatment decisions (Figure 1). Due to the poor outcomes associated with R/R AML, patients should be enrolled in clinical trials where possible (Figure 1). Allogeneic hematopoietic stem cell transplantation (allo-HSCT) rescues around one-third of R/R patients, and a donor search in all transplantable patients should be carried out if not already done at the initial diagnosis.
Figure 1. header...
Allo-HSCT, allogeneic hematopoietic stem cell transplantation; AML, acute myeloid leukemia; BM, bone marrow; BSC, best supportive care; FLAG-Ida, fludarabine, cytarabine, granulocyte colony-stimulating factor, and idarubicin; HAM, high-dose cytarabine, mitoxantrone; HMA, hypomethylating agent; MEC, mitoxantrone, etoposide, cytarabine; R/R, relapsed/refractory; Ven, venetoclax.
*Adapted from Thor, et al.1
†Some patients may go directly to allo-HSCT or receive lower-intensity regimens.
‡Not approved by the European Medicines Agency for patients with R/R AML.
Figure 2. Case study 1 presentation*
AML, acute myeloid leukemia; FLT3, FMS‐like tyrosine kinase 3; ITD, internal tandem duplication; NPM1, nucleophosmin; TET2, tet methylcytosine dioxygenase 2.
*Adapted from Thor, et al.1
Created with BioRender.com.
What does MRD relapse mean, and how can we clinically react to prevent morphological relapse?
How do first-line therapy and mutational profile influence treatment options at relapse?
Figure 3. Case study 2 presentation*
AML, acute myeloid leukemia; ASXL1, additional sex comb-like 1; IDH2, isocitrate dehydrogenase 2; NF1, neurofibromatosis 1.
*Adapted from Thor, et al.1
Created with BioRender.com.
What is the outlook for R/R AML patients after treatment with azacitidine/venetoclax, and what are their treatment options?
Figure 4. Case study 3 presentation*
AML, acute myeloid leukemia; DNMT3A, DNA methyltransferase 3 alpha; ECOG, Eastern Cooperative Oncology Group; NRAS, neuroblastoma RAS viral oncogene homolog; TP53, tumor protein p53.
*Adapted from Thor, et al.1
Created with BioRender.com.
How could we prevent relapse after allo-HSCT in this patient, and what can we do if relapse occurs?
The landscape of treatment for patients with R/R AML is evolving. Triplet combinations of azacitidine and venetoclax plus targeted therapy or novel agents are currently being investigated, with promising initial results. Novel immunotherapies, including chimeric antigen receptor T cells, bispecific T-cell engaging antibodies, or dual-affinity retargeting antibodies are currently under evaluation. However, substantial effort is required to improve outcomes for this patient population.
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