Clinical potential of introducing next‐generation sequencing in patients at relapse of acute myeloid leukemia

Relapse of acute myeloid leukemia (AML) remains a major determinant of outcome. A number of molecularly directed treatment options have recently emerged making comprehensive diagnostics an important pillar of clinical decision making at relapse. Acknowledging the high degree of individual genetic va...

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Bibliographic Details
Published in:Hematological oncology 2020-10, Vol.38 (4), p.425-431
Main Authors: Flach, Johanna, Shumilov, Evgenii, Wiedemann, Gertrud, Porret, Naomi, Shakhanova, Inna, Bürki, Susanne, Legros, Myriam, Joncourt, Raphael, Pabst, Thomas, Bacher, Ulrike
Format: Article
Language:English
Subjects:
Acute myeloid leukemia
acute myeloid leukemia (AML)
Decision making
Devolution
Genetic variability
Inhibitors
Leukemia
minimal residual disease (MRD)
Mutation
Myeloid leukemia
next‐generation sequencing (NGS)
Patients
relapse
Stem cell transplantation
Stem cells
Transplantation
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Summary:Relapse of acute myeloid leukemia (AML) remains a major determinant of outcome. A number of molecularly directed treatment options have recently emerged making comprehensive diagnostics an important pillar of clinical decision making at relapse. Acknowledging the high degree of individual genetic variability at AML relapse, next‐generation sequencing (NGS) has opened the opportunity for assessing the unique clonal hierarchy of individual AML patients. Knowledge on the genetic makeup of AML is reflected in patient customized treatment strategies thereby providing improved outcomes. For example, the emergence of druggable mutations at relapse enable the use of novel targeted therapies, including FLT3 inhibitors or the recently approved IDH1/2 inhibitors ivosidenib and enasidenib, respectively. Consequently, some patients may undergo novel bridging approaches for reinduction before allogeneic stem cell transplantation, or the identification of an adverse prognostic marker may initiate early donor search. In this review, we summarize the current knowledge of NGS in identifying clonal stability, clonal evolution, and clonal devolution in the context of AML relapse. In light of recent improvements in AML treatment options, NGS‐based molecular diagnostics emerges as the basis for molecularly directed treatment decisions in patients at relapse.
ISSN:0278-0232
1099-1069
DOI:10.1002/hon.2739