Page 76 - 2019_08-Haematologica-web

M. Sebert et al.
failure in one, and from unknown cause in five. None of the patients had received allogeneic SCT.
Prognostic factors of response and overall survival
Response was seen in four (26%) of the 15 patients with primary failure, and four (9%) of the 41 relapsing patients (P=0.12). The median number of mutations was one [range, 0-3 in responders, compared with 2 (range, 0- 6) mutations in non-responders (P=0.035)], and the response rate was significantly higher in patients with no
detectable somatic mutations compared to patients with at least one somatic mutation (P=0.036). None of the 11 patients with TP53 mutation achieved response. Clonal architecture was followed during treatment in five responders with mutations at baseline. There was no sig- nificant decrease in VAF of the mutated clone(s) at hema- tologic response (Figure 2B). Treatment with guadecitabine resulted in a maximum LINE-1 demethyla- tion relative to baseline (D0) of 12.3% on day 8 of cycle 1 in peripheral blood samples and of 3.3% on day 28 of
A
Figure 2. Molecular characteristics of the patients after azacitidine (AZA) failure and dur- ing guadecitabine treatment. (A) Spectrum of mutations in the 56 high-risk myelodypslastic syndrome (MDS) patients included (refractory to or relapsing after AZA therapy) in 36 selected genes. Each column represents an individual patient sample, and each colored cell represents a mutation of the gene or gene group listed to the left of that row. The number of mutations in each row is indicated in the column on the right. Darker cells of patient numbers indicate respon- ders to guadecitabine. (B) Evolution of different clones, according to variant allele frequency (VAF), in five patients responding to guadecitabine after AZA failure.
B
1568
haematologica | 2019; 104(8)