1. TP53 mutant status significantly associated with bone marrow blast clearance after treatment with decitabine in patients with acute myelogenous leukemia (AML) or myelodysplastic syndromes (MDS).
Evidence Rating Level: 2 (good)
Study Rundown: AML and MDS are clonal myeloid neoplasms. Decitabine is a hypomethylating agent that promotes re-expression of tumor suppressor genes, and is commonly used as a single-agent therapy in treating AML and MDS. In this prospective cohort study, researchers evaluated whether molecular determinants such as mutation status, in adult patients age ≥60 with AML, relapsed AML or transfusion-dependent MDS, impact clinical response to 10-day decitabine treatment. Overall, they found that AML and MDS patients categorized as having unfavorable-risk cytogenetic profiles, TP53 mutations or both, had significant clinical responses and mutation clearance after decitabine treatment. However, the authors note that while single-therapy decitabine is not a cure for AML and MDS, as rapid selection of resistant subclones frequently occurs after decitabine treatment, this therapy may nonetheless become an important way of inducing clinical remission.
Click to read the study, published in NEJM
Relevant Reading: Decitabine in the treatment of acute myeloid leukemia in elderly patients
In-Depth [prospective cohort]: In this prospective cohort study, 116 patients received a 10-day course of decitabine on days 1-10 of a 28-day. 84 patients received decitabine on days 1-10 of a 28-day cycle (median of two cycles) at Washington University in St. Louis. Response criteria categories were used per the International Working Group for AML and MDS and bone marrow samples were collected on days 0, 10 and 28 of cycle 1. The overall response rate was 46% – 15 of the 116 (13%) patients achieved complete remission and 38 (33%) had bone marrow clearance with ≤5% blasts. Overall, 54 patients had enhanced exome sequencing performed on them. 40% of the sequenced patients who had a response that included complete remission, complete remission with incomplete count recovery or morphologic complete remission also had TP53 mutations (p < 0.001). Bone marrow blast clearance occurred in 29 of 43 (67%) patients with unfavorable-risk karyotype, 24 of 71 (34%) patients intermediate risk karyotype (p < 0.001). Clearance also occurred in 21 of 21 (100%) of patients with TP53 mutations vs. 32 of 78 (41%) patients with wild-type TP53 mutations (p < 0.001).
Image: PD
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