Genetic Risk Stratification and Outcomes Among Treatment-Naive Patients With AML Treated With Venetoclax and Azacitidine.

Autor:	Döhner H; Department of Internal Medicine III, Ulm University Hospital, Ulm,, Germany., Pratz KW; Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, United States., DiNardo CD; Department of Leukemia, Division of Cancer Medicine, University of Texas M.D. Anderson Cancer Center, Houston, TX, United States., Wei AH; Department of Clinical Haematology, Peter MacCallum Cancer Centre, Royal Melbourne Hospital, Walter and Eliza Hall Institute of Medical Research and University of Melbourne, Melbourne, Australia., Jonas BA; Department of Internal Medicine, Division of Malignant Hematology/Cellular Therapy, and Transplantation, University of California Davis School of Medicine, Sacramento, CA, United States., Pullarkat V; Department of Hematology and Hematopoietic Cell Transplantation and Gehr Family Center for Leukemia Research, City of Hope Comprehensive Cancer Center, Duarte, CA, United States., Thirman MJ; Section of Hematology and Oncology, Department of Medicine, University of Chicago Medicine, Chicago, IL, United States., Récher C; CHU de Toulouse, Toulouse, France., Schuh AC; Princess Margaret Cancer Centre, Toronto, Canada., Babu S; Fort Wayne Medical Oncology and Hematology, Fort Wayne, IN, USA; 11AbbVie Inc., North Chicago, IL, United States., Li X; AbbVie Inc., North Chicago, Illinois, United States., Ku G; Genentech, Inc., South San Francisco, California, United States., Liu Z; AbbVie Inc., new brunswick, New Jersey, United States., Sun Y; AbbVie, Inc, North Chicago, Illinois, United States., Potluri J; AbbVie, North Chicago, Illinois, United States., Dail M; Genentech, Inc., South San Francisco, California, United States., Chyla B; Abbvie, North Chicago, Illinois, United States., Pollyea DA; University of Colorado Division of Hematology, School of Medicine, Aurora, CO, United States.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2024 Aug 12. Date of Electronic Publication: 2024 Aug 12.
DOI:	10.1182/blood.2024024944
Abstrakt:	European LeukemiaNet (ELN) acute myeloid leukemia (AML) genetic risk classification systems were based on response to intensive chemotherapy; their ability to discriminate outcomes in older patients treated with venetoclax-azacitidine may be suboptimal. Here, pooled analysis of patients in the phase 3 VIALE-A trial (NCT02993523) and phase 1b study (NCT02203773) examined prognostic stratification according to 2017 and 2022 ELN risk classifications. A bioinformatic algorithm derived new molecular signatures differentiating venetoclax-azacitidine-treated patients based on median overall survival (OS). 279 patients treated with venetoclax-azacitidine and 113 patients treated with placebo-azacitidine were analyzed. When classified by ELN 2017 or 2022 prognostic criteria, most patients had adverse-risk AML (60.2% and 72.8% for venetoclax-azacitidine and 65.5% and 75.2% for placebo-azacitidine, respectively). While outcomes with venetoclax-azacitidine were improved across all ELN risk groups compared with placebo-azacitidine, ELN classification systems poorly discriminated venetoclax-azacitidine outcomes. By applying a bioinformatic algorithm, new molecular signatures were derived differentiating OS outcomes with venetoclax-azacitidine; the mutational status of TP53, FLT3-ITD, NRAS, and KRAS categorized patients into higher-, intermediate-, and lower-benefit groups (52%, 25%, and 23% of patients, respectively), each associated with a distinct median OS (26.5 months [95% CI, 20.2 to 32.7], 12.1 months [95% CI, 7.3 to 15.2], and 5.5 months [95% CI, 2.8 to 7.6], respectively). ELN prognostic classifiers do not provide clinically meaningful risk stratification of OS outcomes for patients with AML treated with venetoclax-azacitidine. TP53, FLT3-ITD, NRAS, and KRAS mutation status allows classification of these patients into three risk groups with distinct differences in median OS. (Copyright © 2024 American Society of Hematology.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu