Circulating Tumor DNA Early Kinetics Predict Response of Metastatic Melanoma to Anti-PD1 Immunotherapy: Validation Study

Autor: Audrey Vallée, Amir Khammari, Brigitte Dréno, Anne-Chantal Knol, Guillaume Herbreteau, Emilie Varey, Marc G. Denis, Sandrine Théoleyre, Gaëlle Quéreux
Přispěvatelé: Clinical and Translational Research in Skin Cancer (CRCINA-ÉQUIPE 2), Centre de Recherche en Cancérologie et Immunologie Nantes-Angers (CRCINA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR de Médecine et des Techniques Médicales (UFR MEDECINE), Université de Nantes (UN)-Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Centre National de la Recherche Scientifique (CNRS)-Université d'Angers (UA), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre d’Investigation Clinique de Nantes (CIC Nantes), Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre hospitalier universitaire de Nantes (CHU Nantes), Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes)-Université d'Angers (UA)-Université de Nantes (UN)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Khammari, Amir
Rok vydání: 2021
Předmět:
0301 basic medicine
Oncology
Neuroblastoma RAS viral oncogene homolog
Cancer Research
medicine.medical_specialty
Metastatic melanoma
medicine.medical_treatment
[SDV.CAN]Life Sciences [q-bio]/Cancer
lcsh:RC254-282
Article
cell-free DNA
03 medical and health sciences
0302 clinical medicine
[SDV.CAN] Life Sciences [q-bio]/Cancer
Internal medicine
medicine
follow-up
melanoma
Digital polymerase chain reaction
anti-PD1
Anti pd1
circulating tumor DNA
criteria
business.industry
digital PCR
Melanoma
Immunotherapy
[SDV.IMM.IMM]Life Sciences [q-bio]/Immunology/Immunotherapy
medicine.disease
lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens
3. Good health
monitoring
030104 developmental biology
Cell-free fetal DNA
Circulating tumor DNA
030220 oncology & carcinogenesis
immunotherapy
[SDV.IMM.IMM] Life Sciences [q-bio]/Immunology/Immunotherapy
business
metastatic melanoma
Zdroj: Cancers
Cancers, MDPI, 2021, 13 (8), pp.1826. ⟨10.3390/cancers13081826⟩
Cancers, Vol 13, Iss 1826, p 1826 (2021)
Cancers, 2021, 13 (8), pp.1826. ⟨10.3390/cancers13081826⟩
Volume 13
Issue 8
ISSN: 2072-6694
DOI: 10.3390/cancers13081826⟩
Popis: The ability of early (first weeks of treatment) ctDNA kinetics to identify primary resistance to anti-PD1 immunotherapies was evaluated with a validation cohort of 49 patients treated with anti‑PD1 for metastatic BRAF or NRAS-mutated melanoma, alone and pooled with the 53 patients from a previously described derivation cohort. BRAF or NRAS mutations were quantified on plasma DNA by digital PCR at baseline and after two or four weeks of treatment. ctDNA kinetics were interpreted according to pre-established biological response criteria. A biological progression (bP, i.e., a significant increase in ctDNA levels) at week two or week four was associated with a lack of benefit from anti-PD1 (4-month PFS = 0%
1‑year OS = 13%
n = 12/102). Patients without initial bP had significantly better PFS and OS (4-month PFS = 78%
1‑year OS = 73%
n = 26/102), as did patients whose ctDNA kinetics were not evaluable, due to low/undetectable baseline ctDNA (4-month PFS = 80%
1‑year OS = 81%
n = 64/102). ctDNA detection at first-line anti-PD1 initiation was an independent prognostic factor for OS and PFS in multivariate analysis. Overall, early ctDNA quantitative monitoring may allow the detection of primary resistances of metastatic melanoma to anti-PD1 immunotherapies.
Databáze: OpenAIRE
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