Genomic landscape of myelodysplastic/myeloproliferative neoplasm can predict response to hypomethylating agent therapy

Abstract

There are currently no known predictors of myelodysplastic syndrome (MDS)/myeloproliferative overlap neoplasm (MPN) patients’ response to hypomethylating agents (HMA). Forty-three patients with MDS/MPN who were treated with HMA during chronic phase and had next-generation sequencing using the established 63-genes panel were identified. Complete and partial remission and marrow response were assessed based on the MDS/MPN International Working Group response criteria. On univariate analysis, younger age, higher number of mutations, and mutations in SETBP1, RUNX1, or EZH2 were associated with no response. Multivariable analysis for modeling response were conducted via least absolute shrinkage and selection operator logistic regression approach, and showed that mutations in SETBP1, RUNX1, or EZH2 predict lack of HMA response. While limited by sample size, our findings suggest that genomic landscape can potentially identify MDS/MPN patients with lower likelihood of response to HMA.

Keywords:

• MDS/MPN
• HMA
• genomics
• response
• survival

Author contributions

T.K. and T.J. conceptualized the project, wrote the first draft of the manuscript, and were responsible for acquiring, analyzing, and interpreting the data. H-L.T. and R.V. conducted the statistical analysis. L.P.G. and A.E.D. contributed to data acquisition and analysis. All the other authors contributed to the collection of data, revising the manuscript critically for important intellectual content. All authors approved the final version of the manuscript. T.K. and T.J. are accountable for all aspects of the work related to accuracy and integrity

Disclosure statement

T.J. has institutional research support from CTI Biopharma, Syneos Health, Incyte; Consultancy with Targeted Healthcare Communications; Advisory board participation with Care Dx, Bristol Myers Squibb, and CTI. J.W. does consultancy for Amgen and Pfizer. The remaining authors declare no competing interest.

Additional information

Funding

TK was funded by T32HL007525 NIH/NHLBI and the ASH Research Training Award for Fellows.