Cytogenetics and mutations could predict outcome in relapsed and refractory acute myeloid leukemia patients receiving BCL-2 inhibitor venetoclax
Journal
Annals of hematology
Journal Volume
99
Journal Issue
3
Pages
501
Date Issued
2020-03
Author(s)
Wang, Yu-Wen
Chen, Yu-Wen
HSIN-YI LIN
Lin, Chien-Ting
Abstract
Venetoclax, a selective B cell leukemia/lymphoma-2 (BCL2) inhibitor, has recently shown activity in relapsed or refractory (R/R) acute myeloid leukemia (AML). Effective biomarkers for identifying patients most likely to respond to venetoclax-based treatment are of clinical utility. In this study, we aimed to evaluate the efficacy and safety profiles of venetoclax-based therapy in a total 40 R/R AML patients and identify the potentially predictive factors for response. Overall response rate was 50%, including 9 (22.5%) complete response (CR) or CR with incomplete hematologic recovery of either neutrophil or platelet counts (CRi). Median time to best response was 1.4 months and the median overall survival (OS) was 6.6 months. Presence of intermediate-risk cytogenetics predicted better OS compared to unfavorable-risk cytogenetics. Patients harboring NPM1, RUNX1, or SRSF2 mutations seemed to have higher CR/CRi rates and median OS was significantly longer in RUNX1-mutated patients. On the contrary, patients with FLT3-ITD, TP53, or DNMT3A mutations did not reach any objective response and had worse OS. No laboratory or clinical tumor lysis syndrome was observed and the most common adverse events were prolonged cytopenias which resulted in 67.5% of febrile neutropenia. Patients with concurrent use of azole antifungals had similar incidence of cytopenias compared with those without azole antifungals. In summary, we demonstrate that venetoclax is an effective and well-tolerated salvage option for R/R AML patients. Survival benefits were particularly remarkable in patients with intermediate-risk cytogenetics or RUNX1 mutations. In contrast, TP53, NRAS, and DNMT3A mutations as well as FLT3-ITD conferred negative impact on survival.
Subjects
Acute myeloid leukemia; Mutations; Refractory; Relapse; Venetoclax
SDGs
Other Subjects
CD135 antigen; DNA methyltransferase 3A; febuxostat; nucleophosmin; protein bcl 2; protein p53; transcription factor RUNX1; venetoclax; BCL2 protein, human; fused heterocyclic rings; protein bcl 2; sulfonamide; venetoclax; acute myeloid leukemia; adult; aged; Article; bacteremia; cancer chemotherapy; cancer survival; candidiasis; clinical article; clinical effectiveness; clinical evaluation; cytogenetics; cytopenia; DNMT3A gene; drug effect; drug safety; febrile neutropenia; female; FLT3 gene; gene mutation; human; intermediate risk patient; leukemia relapse; male; middle aged; mutator gene; mycobacteriosis; neutrophil count; NPM1 gene; outcome assessment; overall survival; platelet count; prediction; priority journal; RUNX1 gene; SRSF2 gene; survival rate; survival time; systemic mycosis; tumor lysis syndrome; tumor suppressor gene; clinical trial; cytogenetics; disease free survival; febrile neutropenia; genetics; mortality; mutation; risk factor; very elderly; Adult; Aged; Aged, 80 and over; Bridged Bicyclo Compounds, Heterocyclic; Cytogenetics; Disease-Free Survival; Febrile Neutropenia; Female; Humans; Leukemia, Myeloid, Acute; Male; Middle Aged; Mutation; Proto-Oncogene Proteins c-bcl-2; Risk Factors; Sulfonamides; Survival Rate
Publisher
SPRINGER