Whether it is feasible to obtain patient genomic data for precision therapy
Last Update: 2021-02-24
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precision therapy has always been the ideal treatment strategy pursued by clinical medicine, and many clinical trials and scientific research work have been carried out to this end, from the clinical characteristics of the disease to its molecular basis, the gap seems difficult to bridge.
Acute myeloid leukemia (AML) is one of the most common leukemias. It is currently believed that acute myeloid leukemia originates from a explicit mutation and then obtains a co-transformation mutation, which leads to myelin transformation and clinical/biological heterogeneity. Many relapsed mutations have been found in patients with acute myeloid leukemia in old age, and their cumulative increase is related to the progress of advanced diseases. Different mutations have different functional effects, including destruction of apoptosis (TP53), production of metabolites (IDH1, IDH2) and lead to oscic genetic remodeling, carcinogenic signals (FLT3, KIT, NRAS, KRAS, PTPN11) and ophthalmological genetic disorders (DNMT3A, TET2, WT1, ASXL1).
On October 26, 2020, the John C. Byrd team at Ohio State University published a paper in the journal Nature Medicine entitled "Precision medicine treatment inacute myeloid leukemia using prospective genomic profiling: feasibility and preleminary efficacy of the Beat AML Master Trial", revealing the feasibility and efficiency of genomic analysis in acute myeloid leukemia treatment for precision medicine.
The researchers included ≥ 60-year-old untreated patients with untreated acute myeloid leukemia in the ongoing Beat acute myeloid leukemia trial, which aims to provide cytogenetic and gene mutation data from patients seven days from the time of receipt of the sample and before the selection of treatment, and then assign the results to a sub-study based on explicit cloning.
The study showed that 487 suspected AML patients were admitted to the group between November 2016 and January 2019. 395 are eligible. The middle age is 72 years (60-92 years; 38% ≥ 75 years). 374 patients (94.7%) completed genetic and cytogenetic analysis within 7 days and were centrally assigned to the Beat AML sub-study.
Of all eligible participants, 224 (56.7%) participated in the BeatAML sub-study. The remaining 171 patients were classified as standard care (SOC) (103), research therapy (28) or palliative care (40);
There was no significant difference in demographic, laboratory, and molecular characteristics between patients in the BeatAML sub-study and those who received SOC (induced with acetic cytosine and erythromycin (7-3 or the same level) or submethylated agents. Patients in the Beat AML sub-study had a lower 30-day mortality rate and significantly longer total survival than those who chose SOC.
As a result, AML's precise drug treatment strategy is feasible within 7 days, allowing patients and doctors to quickly incorporate genomic data into treatment decisions without increasing early death or adversely affecting overall survival.
this forward-looking precision drug trial provides some important insights into future precision drug trials for acute myeloid leukemia and other malignant tumors.
First, the trial showed that for most elderly patients with acute myeloid leukemia, it is safe to delay treatment for detailed molecular spectrum analysis. But patients with rapidly growing diseases or white blood cell stagnation were excluded from the study. Second, this approach requires detailed team coordination efforts by investigators, patients and caregivers, genomics laboratories, cytogenetics laboratories and central treatment distribution teams. Third, most patients with acute myeloid leukemia can carry out specific treatment according to molecular analysis of the cloning of explicit acute myeloid leukemia. Fourth, the experiment also showed that patients who chose to receive treatment based on molecular characteristic analysis had lower early mortality and higher overall survival rates than those who chose to receive SOC. (Biological Exploration)
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