Epigenetic mutations play an important role in the outcomes of elderly patients with acute myeloid leukemia (AML), and understanding these mutations can help guide the use of decitabine-based regimens, according to research published in Hematology.
Elderly patients (age 60 years and older) with AML tend to have a poor prognosis, and improvements in outcomes haven’t advanced for elderly patients as much as for younger patients. This study sought to increase understanding of genetic mutations in elderly adults and how those mutations affect outcomes.
This study analyzed bone marrow cells from 213 patients with newly diagnosed de novo AML. A total of 52 patients were age 60 and older, while 161 patients were younger than 60 years. They also analyzed blood and saliva samples from 79 adults without AML.
Using next generation sequencing techniques the researchers found about 2.79 relevant mutations in each AML sample. A total of 111 genes have mutations associated with AML pathogenesis, and the researchers identified 68 genes of those 111 in the AML patient population.
The most common epigenetic mutations were found in CEBPA (23%), DNMT3A (17.8%), FLT3-ITD (16%), NPM1 (16%), NRAS (13.6%), TET2 (13.6%), and ASXL1 (12.2%).
Chromosome data was available for 50 older patients and 157 younger patients. Older patients tended to have more unfavorable karyotype (26% vs 13.4%), such as complex chromosomal abnormalities, and less favorable karyotypes (4% vs 22.9%) compared to younger patients. Epigenetic mutations in DNMT3A, TET2, ASXL1, and IDH2 were found more frequently in older patients than younger patients.
A total of 39 older patients received a decitabine-based chemotherapy regimen and 30 of those patients had an overall response rate (ORR) of 76.9% after the first cycle. There were 2 patients who had favorable karyotypes both achieved a complete remission (CR), while 8 of 13 patients (61.5%) with unfavorable karyotypes achieved a CR. Patients who received standard chemotherapy achieved a 20% CR rate (1 of 5 patients).
Overall, in this study, patients who received decitabine-based chemotherapy had better complete remission than those receiving standard chemotherapy or palliative care. Based on these results, the authors suggested genotyping to inform targeted therapy options for older adults with AML. However, larger studies will still be needed to confirm and expand upon these results.
Wang B, Guan W, Lv N, et al. Genetic features and efficacy of decitabine-based chemotherapy in elderly patients with acute myeloid leukemia. Hematology. 2021;26(1):371-379. doi:10.1080/16078454.2021.1921434