Impact of numerical variation, allele burden, mutation length and co-occurring mutations on the efficacy of tyrosine kinase inhibitors in newly diagnosed FLT3- mutant acute myeloid leukemia
Autor: | Naval Daver, Courtney D. DiNardo, Ahmad Ghorab, Farhad Ravandi, Allyson Price, Tapan M. Kadia, Naveen Pemmaraju, Gautam Borthakur, Xuemei Wang, Dai Chihara, Fevzi Firat Yalniz, Koji Sasaki, Hagop M. Kantarjian, Keyur P. Patel, Ghayas C. Issa, Jorge E. Cortes, Hyunsoo Hwang, Iman Abou Dalle |
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Jazyk: | angličtina |
Rok vydání: | 2020 |
Předmět: |
Oncology
Adult Male NPM1 medicine.medical_specialty Myeloid Adolescent medicine.medical_treatment lcsh:RC254-282 Article Acute myeloid leukaemia Cytogenetics Young Adult Medical research fluids and secretions Internal medicine hemic and lymphatic diseases Medicine Humans Young adult Protein Kinase Inhibitors Survival analysis Alleles Aged Aged 80 and over Chemotherapy business.industry Myeloid leukemia hemic and immune systems Hematology Middle Aged medicine.disease Prognosis lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Survival Analysis Leukemia Leukemia Myeloid Acute medicine.anatomical_structure Treatment Outcome fms-Like Tyrosine Kinase 3 Mutation embryonic structures Female business Nucleophosmin |
Zdroj: | Blood Cancer Journal, Vol 10, Iss 5, Pp 1-10 (2020) Blood Cancer Journal |
ISSN: | 2044-5385 |
Popis: | FLT3-ITD mutations in newly diagnosed acute myeloid leukemia (AML) are associated with worse overall survival (OS). FLT3-ITD diversity can further influence clinical outcomes. Addition of FLT3 inhibitors to standard chemotherapy has improved OS. The aim of this study is to evaluate the prognostic impact of FLT3 diversity and identify predictors of efficacy of FLT3 inhibitors. We reviewed prospectively collected data from 395 patients with newly diagnosed FLT3-ITD mutant AML. 156 (39%) patients received FLT3 inhibitors combined with either high or low intensity chemotherapy. There was no statistically significant difference in clinical outcomes among patients treated with FLT3 inhibitors based on FLT3 numerical variation (p = 0.85), mutation length (p = 0.67). Overall, the addition of FLT3 inhibitor to intensive chemotherapy was associated with an improved OS (HR = 0.35, 95% CI: 0.24–0.5, p = 0.0005), but not in combination with lower intensity chemotherapy (HR = 0.98, 95%CI: 0.7–1.36, p = 0.85). A differential effect of FLT3 inhibitor on OS was more pronounced in younger patients with FLT3 allelic ratio ≥0.5 (HR = 0.41, 95% CI: 0.25–0.66, p p = 0.01), diploid cytogenetics (HR = 0.52, 95% CI: 0.35–0.76, p = 0.001), NPM1 co-mutation (HR = 0.35, 95% CI: 0.19–0.67, p = 0.001). Our analysis identifies predictors of survival among diverse FLT3 related variables in patients treated with FLT3 inhibitor. |
Databáze: | OpenAIRE |
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