Getting personal with myelodysplastic syndromes: is now the right time?

ABSTRACT

Introduction: Commonly used scoring systems rely on blood counts, histological and cytological examination of bone marrow and peripheral blood as well as cytogenetic assessments to estimate prognosis of patients with myelodysplastic syndromes (MDS) and guide therapy decisions. Next-generation sequencing (NGS) has identified recurrent genetic abnormalities in up to 90% of patients with MDS and may provide important information regarding the pathogenesis of the disease, diagnostic and prognostic evaluation, and therapy selection.

Areas covered: Herein, the authors review the role of NGS in diagnosis, treatment, and prognosis of MDS at various disease stages, and discuss advantages and caveats of incorporating molecular genetics in routine management of MDS. While a vast majority of patients harbor recurrent mutations implicated in MDS pathogenesis, similar mutations can be detected in otherwise healthy individuals with other hematologic malignancies. Besides establishing a diagnosis, NGS may be used to monitor minimal residual disease following treatment.

Expert opinion: As more targeted therapies become available, assessment of genetic mutations will become central to individualized therapy selection and may improve diagnostic accuracy and further guide management for each patient. However, multiple challenges remain before NGS can be incorporated into routine clinical practice.

KEYWORDS:

• Genetics
• myelodysplastic syndrome
• MDS
• mutations
• next generation sequencing
• NGS

Article highlights

• Next-generation sequencing (NGS) is a highly sensitive method to detect specific mutations in the blood and bone marrow of patients with hematologic disorders and can be helpful to distinguish morphologically similar appearing conditions.

• NGS may have additional diagnostic, therapeutic, and prognostic value when combined with established risk stratification tools.

• As of now, there is insufficient evidence to base treatment choices on NGS-based mutational testing, although there is increasing data that show that the presence or absence of specific genetic mutations may confer a higher or lower likelihood of response to a certain treatment.

• Major limitations to the routine use of NGS in MDS include the genetic heterogeneity, the small clonal size, a lack of understanding of the impact of a certain mutation and the combination of various mutations on prognosis and treatment response, and the high cost in the absence of a clear benefit for patients.

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Declaration of interest

AM Zeidan has received research funding (institutional) from Celgene, Acceleron, Abbvie, Otsuka, Pfizer, Medimmune/AstraZeneca, Boehringer-Ingelheim, Trovagene, Incyte, Takeda, and ADC Therapeutics. AM Zeidan had a consultancy with and received honoraria from AbbVie, Otsuka, Pfizer, Celgene, Ariad, Incyte, Agios, Boehringer-Ingelheim, Novartis, Acceleron, Astellas, Daiichi Sankyo, Cardinal Health, Seattle Genetics, BeyondSpring, and Takeda. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or conflict with the subject matter or materials discussed in this manuscript apart from those disclosed.

Reviewer disclosures

Peer reviewers on this manuscript have no relevant financial or other relationships to disclose.

Additional information

Funding

AM Zeidan is a Leukemia and Lymphoma Society Scholar in Clinical Research and is also supported by a NCI’s Cancer Clinical Investigator Team Leadership Award (CCITLA). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number P30 CA016359. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.