Page 104 - 2019_02-Haematologica-web

C.Y. Ok et al.
between patients in the high and low MAF groups (6.2 and 9.9 months, respectively) was not statistically signifi- cant (P=0.18). We also assessed different MAF as cutoffs for high versus low mutation burden (5%, 20% and 30%), but correlation with relapse was not observed using any of these cutoffs (data not shown).
IDH mutations in remission predict relapse in the context of co-mutations
Other gene mutations were detected in 89% of patients who had IDH1/2 mutations in a pre-treatment sample.
NPM1 (n=38) was the most frequently co-mutated gene followed by DNMT3A R882 (n=25), FLT3-ITD (internal tandem duplication) (n=22), and KRAS/NRAS (n=12). Few (<5) patients had mutations in ASXL1, BRAF, CEBPA, JAK2, RUNX1, TET2 or TP53. CRIDH+ was significantly more common (39%) than CRFLT3+ (n=3, 14%), CRNPM1+ (n=4, 11%), and CRKRAS/NRAS+ (n=0, 0%) in CR or CRi (P>0.05). CRDNMT3A+ was present with a similar frequency, being seen in 36% of patients (n=9). We assessed the effect of CRIDH+ in the context of co-mutations using the Fine and Gray regression model. By univariate analysis,
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Figure 1. Persistent IDH1/2 mutations in remission and changes in mutant allelic frequencies in pretreatment and remission samples. (A) Percentages of persist- ent IDH1/2 mutations in patients with acute myeloid leukemia in remission. Persistent mutations occur at similar frequencies for the different mutations. (B) Mutant allelic frequency (MAF) of IDH mutations present in pretreatment samples and remission samples. The median mutant allelic frequency is shown for each occasion.
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Figure 2. Cumulative incidence rates of relapse in patients with persistent IDH1/2 mutations in remission. (A) Cumulative incidences of relapse in patients with persistent IDH1/2 mutation and patients without detectable IDH1/2 mutation. The cumulative incidence rate is significantly higher in patients with persistent IDH1/2 mutation in remission (CRIDH+) than in patients without detectable IDH1/2 mutation in remission (CRIDH-). (B) Cumulative incidence rate of relapse in patients with respect to mutational status in IDH1/2 and flow cytometrically determined presence of minimal residual disease in remission. The cumulative incidence of relapse was significantly higher in patients who were positive in both molecular and flow cytometry tests compared to patients with a positive result in either of the tests or negative in both. CRIDH+; persistent IDH1/2 mutation in remission, CRIDH-; non-detectable IDH1/2 mutation in remission, FC+; positive for minimal residual dis- ease by flow cytometry, FC–; negative for minimal residual disease by flow cytometry.
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