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| Item Type: | Article |
|---|---|
| Title: | Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care |
| Creators Name: | Döhner, H., Dolnik, A., Tang, L., Seymour, J.F., Minden, M.D., Stone, R.M., Del Castillo, T.B., Al-Ali, H.K., Santini, V., Vyas, P., Beach, C L., MacBeth, K.J., Skikne, B.S., Songer, S., Tu, N., Bullinger, L. and Dombret, H. |
| Abstract: | Older patients with newly diagnosed acute myeloid leukemia (AML) in the phase 3 AZA-AML-001 study were evaluated at entry for cytogenetic abnormalities, and a subgroup of patients was assessed for gene mutations. Patients received azacitidine 75 mg/m/day x7 days (n = 240) or conventional care regimens (CCR; n = 245): intensive chemotherapy, low-dose cytarabine, or best supportive care only. Overall survival (OS) was assessed for patients with common (occurring in ≥10% of patients) cytogenetic abnormalities and karyotypes, and for patients with recurring gene mutations. There was a significant OS improvement with azacitidine vs CCR for patients with European LeukemiaNet-defined Adverse karyotype (HR 0.71 [95%CI 0.51-0.99]; P = 0.046). Azacitidine-treated patients with -5/5q-, -7/7q-, or 17p abnormalities, or with monosomal or complex karyotypes, had a 31-46% reduced risk of death vs CCR. The most frequent gene mutations were DNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), and TP53 (21%). Compared with wild-type, OS was significantly reduced among CCR-treated patients with TP53 or NRAS mutations and azacitidine-treated patients with FLT3 or TET2 mutations. Azacitidine may be a preferred treatment for older patients with AML with Adverse-risk cytogenetics, particularly those with chromosome 5, 7, and/or 17 abnormalities and complex or monosomal karyotypes. The influence of gene mutations in azacitidine-treated patients warrants further study. |
| Keywords: | Acute Myeloid Leukemia, Antineoplastic Antimetabolites, Azacitidine, Cytarabine, Cytogenetics, Karyotype, Mutation |
| Source: | Leukemia |
| ISSN: | 1476-5551 |
| Publisher: | Nature Publishing Group |
| Volume: | 32 |
| Number: | 12 |
| Page Range: | 2546-2557 |
| Date: | December 2018 |
| Official Publication: | https://doi.org/10.1038/s41375-018-0257-z |
| PubMed: | View item in PubMed |
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