Impact of next generation sequencing results on clinical management in patients with hematological disorders

Abstract

Application of next generation sequencing (NGS) has shed light on the molecular heterogeneity of hematological malignancies. NGS panels targeting recurrent mutations have become common in many large centers and commercial laboratories. However, its impact in clinical practice is unclear. We sought to characterize the use of NGS at a tertiary care center in an observational study of 343 patients with suspected hematological malignancies. We found that NGS changed or refined the clinical and pathologic diagnosis in 9% of patients and affected management decisions in 65% (including clinical trial eligibility, targeted therapy selection, and consideration for stem cell transplantation). This study emphasizes early incorporation of NGS in clinical practice while also highlighting the present limitations. As our understanding of these disorders increases and more clinically relevant genetic targets emerge, it will be important to refine the molecular testing strategy to deliver personalized medicine given the high cost associated with this technology.

Keywords:

• Next generation sequencing
• myeloid neoplasms
• somatic mutation
• AML
• MDS/MPN
• clinical outcomes

Author contributions

B.J.P and S.V. B. designed the study, collected, analyzed and interpreted data and wrote the manuscript. Y.X. collected and analyzed the clinical data. J. R. C, H. E.C and E.D.H. designed the study, analyzed and interpreted data, and edited the manuscript.

Disclosure statement

B.J.P., S.V.B., Y.X. and J.R.C declare no conflict of interest. E.D.H: Advisory board/consultancy – Seattle Genetics, Miltenyi; Research funding: Eli Lilly, Abbvie. H.E.C: Research support from BMS/Celgene for an investigator-initiated study and Sydax also supplies drug (only). Consultant/speaker for BMS, Agios, Stemline, Novartis, Jazz and has served on advisory boards for BMS, Celgene, Agios, Abbvie, Novartis, Stemline and Jazz. Serves on Independent Review Committees for Takeda, ASTX and also for Abbvie.