2. Academic Validation
  3. 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

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. doi: 10.1038/s41392-023-01614-1.
Ruoyang Shao # 1 2,  Yu Zhang # 1 2,  Jinping He # 1 2,  Fen Huang # 1 2,  Zhiping Fan # 1 2,  Kaibo Yang 1 2,  Yajing Xu 3,  Na Xu 1 2,  Yi Luo 4,  Lan Deng 5 6,  Xi Zhang 7,  Jia Chen 8,  Mingzhe Han 9,  Xudong Li 10,  Sijian Yu 1 2,  Hui Liu 1 2,  Xinquan Liang 11,  Xiaodan Luo 12 13,  Pengcheng Shi 1 2,  Zhixiang Wang 1 2,  Ling Jiang 1 2,  Xuan Zhou 1 2,  Ren Lin 1 2,  Yan Chen 3,  Sanfang Tu 5,  Jing Sun 1 2,  Yu Wang 14,  Qifa Liu 15 16 17,  Li Xuan 18 19
Affiliations

Affiliations

  • 1 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China.
  • 2 Clinical Medical Research Center of Hematology Diseases of Guangdong Province, Guangzhou, 510515, China.
  • 3 Department of Hematology, Xiangya Hospital, Central South University, Changsha, 410008, China.
  • 4 Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou, 310009, China.
  • 5 Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, 510280, China.
  • 6 Department of Hematology, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, 200125, China.
  • 7 Department of Hematology, Xinqiao Hospital, Third Military Medical University, Chongqing, 400037, China.
  • 8 The First Affiliated Hospital of Soochow University, Suzhou, 215006, China.
  • 9 Hematopoietic Stem Cell Transplantation Center, Institute of Hematology and Blood Diseases Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Tianjin, 300020, China.
  • 10 Department of Hematology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, 510630, China.
  • 11 Department of Hematology, the First People's Hospital of Chenzhou, Chenzhou, 423099, China.
  • 12 Department of Hematology, the First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, China.
  • 13 Department of Hematology, the Fifth Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510799, China.
  • 14 Department of Hematology, Peking University People's Hospital, Beijing, 100044, China. [email protected].
  • 15 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 16 Clinical Medical Research Center of Hematology Diseases of Guangdong Province, Guangzhou, 510515, China. [email protected].
  • 17 Guangdong Provincial Key Laboratory of Digital Medicine and Biomechanics, National Key Discipline of Human Anatomy, School of Basic Medical Sciences, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 18 Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, China. [email protected].
  • 19 Clinical Medical Research Center of Hematology Diseases of Guangdong Province, Guangzhou, 510515, China. [email protected].
  • # Contributed equally.
PMID: 37704613 DOI: 10.1038/s41392-023-01614-1
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.

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