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Clinical relevance of genetic mutation on treatment response to demethylating agents in myelodysplastic syndromes

Date

21 Dec 2015

Session

Haematological malignancies

Presenters

Hyun Ae Jung

Citation

Annals of Oncology (2015) 26 (suppl_9): 85-92. 10.1093/annonc/mdv526

Authors

H.A. Jung1, J.H. Jang2

Author affiliations

  • 1 Department Of Medidine, Dongtan Sacred Heart Hospital, 445-907 - HwaSeong-Si/KR
  • 2 Department Of Medidine, Samsung Medical Center Sungkyunkwan University School of Medicine, 135-710 - Seoul/KR
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Abstract 440

Aim/Background

In the post-epigenetic therapy era, treatment approaches for patients with MDS have improved significantly over the last decade, especifically, in terms of quality of life and leukemic transformation and survival. Unlike, conventional chemotherapy, it often takes several cycles of hypomethylating agent to visualize the effect of the therapy. However, previous study had heterogenous study populations and had low response rate to hypomethylating agent. We investigate the prevalence of recurrent genetic mutations in de novo MDS patients and elucidate the prognostic and predictive role of mutations on the 1st line decitabine treatment in MDS.

Methods

We investigated genes including methylating machinery genes (TET3 and DNMT2) by Sanger sequencing in patients who were diagnosed with de novo MDS at Samsung medical Center between June 2008 and December 2011 and who were treated with 1st line 5-day regimen of decitabine treatment.

Results

We analyzed clinical data including treatment outcomes in 70 patients (total 290 cycles). The overall response (complete remission, partial remission, marrow complete remission and hematologic improvement) rate was 52.5%. The median time to any response was two (range 1-6). Patients who showed hematologic improvements had significantly longer survival than those who did not (9.8 vs 22.9 months, P-value = 0.004). The prevalence of mutations in the methylating machinery genes were 17.1% (N = 12). In the baseline characteristic between wild type and mutated genes, there was no significant difference. The overall response rate was significantly higher in the patient who had the mutations in methylating machinery genes (43.1% vs 83.3%, P-value = 0.023).

Conclusions

The current results showed that methylating machinery gene TET2MUT, DNMT3AMUT had clinical relevance as preditive biomarker for hypomethylating agents.

Clinical trial identification

Disclosure

All authors have declared no conflicts of interest.

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