Cytogenetics and gene mutations influence survival in older patients with acute myeloid leukemia treated with azacitidine or conventional care. Issue 12 (December 2018)

• Record Type: Journal Article
• Authors: Döhner, Hartmut; Dolnik, Anna; Tang, Lin; Seymour, John; Minden, Mark; Stone, Richard; del Castillo, Teresa; Al-Ali, Haifa; Santini, Valeria; Vyas, Paresh; Beach, C.; MacBeth, Kyle; Skikne, Barry; Songer, Steve; Tu, Nora; Bullinger, Lars; Dombret, Hervé
• Is Part Of: Leukemia. Volume 32:Issue 12(2018)
• Page Start: 2546
• Page End: 2557
• Publication Date: 2018-12
• Subjects: Leukemia -- Periodicals; 616.99419
• DOI: 10.1038/s41375-018-0257-z
• Languages: English
• ISSNs: 0887-6924

Abstract

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/m2 /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 wereDNMT3A (27%), TET2 (25%), IDH2 (23% [R140, 15%; R172, 8%]), andTP53 (21%). Compared with wild-type, OS was significantly reduced among CCR-treated patients withTP53 orNRAS mutations and azacitidine-treated patients withFLT3 orTET2 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.