Epigenetic modifier gene mutations‐positive AML patients with intermediate‐risk karyotypes benefit from decitabine with CAG regimen. Issue 5 (14th August 2019)

• Record Type: Journal Article
• Authors: Xu, Qingyu; Li, Yan; Jing, Yu; Lv, Na; Wang, Lili; Li, Yonghui; Yu, Li
• Is Part Of: International journal of cancer. Volume 146:Issue 5(2020)
• Page Start: 1457
• Page End: 1467
• Publication Date: 2019-08-14
• Subjects: acute myeloid leukemia with intermediate‐risk karyotypes -- epigenetic modifier gene mutations -- hypomethylating agents -- prognosis; Cancer -- Periodicals; Cancer -- Prevention -- Periodicals; 616.994
• DOI: 10.1002/ijc.32593
• Languages: English
• ISSNs: 0020-7136

Abstract

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. Abstract : What's new? Hypomethylating agent (HMA) decitabine is approved for treating acute myeloid leukemia patients unfit for intensive chemotherapy. However, there is a lack of prognostic and predictive biomarkers for selecting patients who would most benefit from HMAs. The relationship between the therapeutic effects of HMAs and epigenetic modifier gene mutations (EMMs) in patients with cytogenetically intermediate‐risk acute myeloid leukemia (IR‐AML) remains unclear. This study offers evidence that EMMs might serve as biomarkers to predict better response to the regimen of decitabine in combination with cytarabine, aclarubicin hydrochloride, and granulocyte colony‐stimulating factor in IR‐AML patients, indicating their potential capabilities in guiding clinical decisions.