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Impact of genetic patterns on sorafenib efficacy in patients with FLT3-ITD acute myeloid leukemia undergoing allogeneic hematopoietic stem cell transplantation: a multi-center, cohort study. Signal Transduct Target Ther 2023 Sep 14;8(1):348

Date

09/14/2023

Pubmed ID

37704613

Pubmed Central ID

PMC10499827

DOI

10.1038/s41392-023-01614-1

Scopus ID

2-s2.0-85171142787 (requires institutional sign-in at Scopus site)   17 Citations

Abstract

Sorafenib therapy improves overall survival (OS) in patients with FLT3 internal tandem duplication (ITD) acute myeloid leukemia (AML) undergoing allogeneic hematopoietic stem cell transplantation. We explored the efficacy of sorafenib therapy in this population with different concomitant genetic patterns. In this multi-center, cohort study, we enrolled patients with FLT3-ITD AML undergoing allogenic hematopoietic cell transplantation. Patients with sorafenib maintenance post-transplantation for at least four weeks were allocated to the sorafenib group, and otherwise to the control group. Endpoints were OS, disease-free survival, and relapse for the whole cohort and OS for genetic pattern subgroups. Among 613 patients enrolled, 275 were in the sorafenib and 338 the control group. Median follow-up was 36.5 (interquartile range (IQR), 25.2-44.7) months post-transplantation. The 3-year OS post-transplantation was 79.6% (95% confidential interval (CI) 74.8%-84.6%) and 65.2% (95% CI 60.3%-70.6%) (Hazard ratio (HR) 0.50, 95% CI 0.37-0.69; P < 0.0001) in both groups. Sorafenib maintenance post-transplantation improved OS in the favorable (HR 0.33, 95% CI 0.14-0.77; P = 0.011) and adverse (HR 0.56, 95% CI 0.33-0.93; P = 0.026) ELN 2017 risk subgroups. Patients with mutated NPM1, DNMT3A, co-occurring NPM1/DNMT3A, "activated signaling" and "DNA methylation" genes benefited in OS from sorafenib maintenance, while those carrying CEBPA, "tumor suppressors" and "myeloid transcription factors" genes did not. Patients with FLT3-ITDhigh and FLT3-ITDlow AML both benefited in OS from sorafenib maintenance. Our results identify the response of genetic patterns to sorafenib maintenance, providing new viewpoints for the optimal use of sorafenib in FLT3-ITD AML in the transplantation setting.

Author List

Shao R, Zhang Y, He J, Huang F, Fan Z, Yang K, Xu Y, Xu N, Luo Y, Deng L, Zhang X, Chen J, Han M, Li X, Yu S, Liu H, Liang X, Luo X, Shi P, Wang Z, Jiang L, Zhou X, Lin R, Chen Y, Tu S, Sun J, Wang Y, Liu Q, Xuan L

Author

Kaipo Yang Postdoctoral Researcher in the Microbiology and Immunology department at Medical College of Wisconsin




MESH terms used to index this publication - Major topics in bold

Cohort Studies
Hematopoietic Stem Cell Transplantation
Humans
Leukemia, Myeloid, Acute
Nuclear Proteins
fms-Like Tyrosine Kinase 3