Epigenetic modifier gene mutations‐positive AML patients with intermediate‐risk karyotypes benefit from decitabine with CAG regimen

Abstract

It remains unclear whether there is a relationship between therapeutic effects of hypomethylating agents (HMAs) and epigenetic modifier gene mutations (EMMs) in patients with cytogenetically intermediate‐risk acute myeloid leukemia (IR‐AML). Based on targeted‐capture sequencing, we retrospectively analyzed the correlation between EMMs and prognosis in 83 IR‐AML patients treated with decitabine in combination with cytarabine, aclarubicin hydrochloride and granulocyte colony‐stimulating factor (DCAG, n = 35) or “7 + 3” induction regimens (n = 48). In the multivariate analyses, EMM (+) patients did not show any statistically significant difference in remission rates from EMM (−) patients in the DCAG group (p > 0.05), but achieved inferior complete remission (CR; p = 0.03) and overall remission rates (ORR; p = 0.04) after the first course of standard induction regimens (p < 0.05). In the EMM (−) cohort, the DCAG group showed the tendency of adverse total CR (p = 0.06). Besides, DCAG group with EMMs achieved the best survival outcome independent of baseline characteristics, whereas it was opposite in EMM (+) patients receiving standard induction regimens (p < 0.05). Additionally, in the EMM (+) cohort, the survival rate of isolated DCAG group was statistically similar to that of the combination of standard chemotherapies and allogeneic hematopoietic stem cell transplantation (allo‐HSCT) (p > 0.40), whereas patients who received only standard regimens had the worst survival rate (0.0%, p < 0.01). It can be concluded that the EMMs might be regarded as the potentially predictive biomarkers of better response to DCAG in IR‐AML patients.

Mutation profile and prognostic relevance in elderly patients with de novo acute myeloid leukemia treated with decitabine‐based chemotherapy

“…These results suggested that decitabine‐based regimens might improve the unfavorable impact of DNMT3A and TP53 mutations. In line with our data, Xu et al suggested that AML patients with epigenetic modifier gene mutations, including DNMT3A , tended to have better survival when treated with decitabine‐based regimens compared to standard induction chemotherapy 27 . TP53 mutation was reported to be correlated with exceedingly adverse outcomes under intensive chemotherapy modality 28 .…”

Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia

“…In our study, the ORR of DCAG chemotherapy was 76.9%, and 69.2% of patients achieved CR, which showed obvious advantage when compared with standard chemotherapy or palliative treatment. Most patients in our study who were effective with DCAG chemotherapy regimen contained epigenetic modifier gene mutations like IDH1/ IDH2, ASXL1, TET2 or DNMT3A mutations, and this was consistent with our team's previous research [53]. However, due to the limited sample, there were no statistically genetic subgroups that could be most effective with DCAG regimen for these elderly patients.…”

Aberrant DNA methylation in t(8;21) acute myeloid leukemia

“…However, no specific promoter methylation change was found to be correlated with therapy response to HMAs (Issa et al, 2004). While a retrospective study of intermediaterisk patients confirmed a significant positive relationship between epigenetic modifier gene mutations and clinical response to HMAs (Xu et al, 2020a). Consistent with the phenomenon that genetic mutations of DNA methylation regulators contribute to a remarkable change in DNA methylation profiles (Delhommeau et al, 2009).…”