Circulating tumor DNA predicts response in Chinese patients with relapsed or refractory classical hodgkin lymphoma treated with sintilimab

Autor: Chuan Jin, Xinhua Du, Wei Zhang, Yuhuan Gao, Wei Li, Xiong Wang, Yongping Song, Wenqi Jiang, Yuankai Shi, Bo Peng, Hui Zhou, Zhengming Jin, Jianmin Yang, Yan Xiong, Wenbin Qian, Jianfeng Zhou, Lugui Qiu, Ming Hou, Xiuhua Sun, Liqun Zou, Hang Su
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Male
0301 basic medicine
Oncology
Jumonji Domain-Containing Histone Demethylases
Research paper
medicine.medical_treatment
lcsh:Medicine
Gene mutation
Circulating Tumor DNA
ORR
objective response rate
0302 clinical medicine
ctDNA
circulating tumor DNA
Immune Checkpoint Inhibitors
lcsh:R5-920
PET/CT
positron emission tomography and computed tomography
PR
partial remission
HRS
Hodgkin Reed-Sternberg
General Medicine
Middle Aged
Sintilimab
TTR
time to response
Hodgkin Disease
PFS
progression-free survival
DNA-Binding Proteins
030220 oncology & carcinogenesis
Biomarker (medicine)
Female
Immunotherapy
lcsh:Medicine (General)
Receptors
Tumor Necrosis Factor
Member 14
Adult
medicine.medical_specialty
PD
progressive disease
Antineoplastic Agents
VAF
variant allelic frequency
Antibodies
Monoclonal
Humanized
General Biochemistry
Genetics and Molecular Biology
03 medical and health sciences
cHL
classical Hodgkin lymphoma
Internal medicine
Biomarkers
Tumor
medicine
Humans
HL
Hodgkin lymphoma
Progression-free survival
r/r
relapsed or refractory
Genotyping
Aged
PET-CT
business.industry
F-Box Proteins
Classical hodgkin lymphoma
SD
stable disease
lcsh:R
Biomarker
PD-1
programmed cell death-1
CR
complete remission
medicine.disease
Precision medicine
030104 developmental biology
Drug Resistance
Neoplasm
Mutation
anti-PD-1
beta 2-Microglobulin
business
MRI
magnetic resonance imaging
Progressive disease
Transcription Factors
Zdroj: EBioMedicine, Vol 54, Iss, Pp-(2020)
EBioMedicine
ISSN: 2352-3964
Popis: Background: Blood-based biomarker such as circulating tumor DNA (ctDNA) has emerged as a promising tool for assessment of response to immunotherapy in solid tumors; But in hematological malignances, evidences are still lacking to support its clinical utility. In current study the feasibility of ctDNA for prediction and monitoring of response to anti-PD-1 therapy in Chinese patients with relapsed or refractory classical Hodgkin lymphoma (r/r cHL) was assessed. Methods: A total of 192 plasma samples from 75 patients with r/r cHL were collected at baseline and upon therapeutic evaluation. ctDNA were sequenced by targeting panels capturing frequently mutated genes in cHL and other hematological malignancies and then quantified. Analysis on: 1) Gene mutation profile and association of the gene mutations with progression-free survival; 2) Association of pre- and post-treatment ctDNA variant allelic frequencies with clinical outcome; (3) Correlation of the mutated genes with treatment resistance; were performed. Findings: Somatic mutations were detected in 50 out of 61 patients by ctDNA genotyping. The mutations of CHD8 was significantly higher in patients with PFS ≥ 12 months. Baseline ctDNA was significantly higher in responders and a decrease of ctDNA ≥ 40% from baseline indicated superior clinical outcome. Strong agreement between ctDNA dynamic and radiographic response change during therapy was observed in majority of the patients. Furthermore, the mutations of B2M, TNFRSF14 and KDM2B were found to be associated with acquired resistance. Interpretation: ctDNA could be an informative biomarker for anti-PD-1 immunotherapy in r/r cHL. Funding: This work was supported by Innovent Biologics, Eli Lilly and Companyhttps://doi.org/10.13039/501100002852, China National New Drug Innovation Program (2014ZX09201041-001 and 2017ZX09304015), Chinese Academy of Medical Sciences (CAMS) Innovation Fund for Medical Sciences (CIFMS) (2016-I2M-1-001) and National Key Scientific Program Precision Medicine Research Fund of China (2017YFC0909801). The funders had no role in study design, data collection, data analysis, interpretation or writing. Keywords: Circulating tumor DNA, Immunotherapy, anti-PD-1, Biomarker, Classical hodgkin lymphoma, Sintilimab
Databáze: OpenAIRE
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