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Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. / Seremet, Teofila; Jansen, Yanina; Planken, Simon; Njimi, Hassan; Delaunoy, Melanie; El Housni, Hakim; Awada, Gil; Schwarze, Julia Katharina; Keyaerts, Marleen; Everaert, Hendrik; Lienard, Danielle; Del Marmol, Veronique; Heimann, Pierre; Neyns, Bart.

In: Journal of Translational Medicine, Vol. 17, No. 1, 303, 05.09.2019.

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Seremet, Teofila ; Jansen, Yanina ; Planken, Simon ; Njimi, Hassan ; Delaunoy, Melanie ; El Housni, Hakim ; Awada, Gil ; Schwarze, Julia Katharina ; Keyaerts, Marleen ; Everaert, Hendrik ; Lienard, Danielle ; Del Marmol, Veronique ; Heimann, Pierre ; Neyns, Bart. / Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. In: Journal of Translational Medicine. 2019 ; Vol. 17, No. 1.

BibTeX

@article{39872ac8d2bc46f2bf0ebc05dfa65230,
title = "Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy",
abstract = "Background: Treatment with anti-PD1 monoclonal antibodies improves the survival of metastatic melanoma patients but only a subgroup of patients benefits from durable disease control. Predictive biomarkers for durable benefit could improve the clinical management of patients. Methods: Plasma samples were collected from patients receiving anti-PD1 therapy for ctDNA quantitative assessment of BRAFV600 and NRASQ61/G12/G13 mutations. Results: After a median follow-up of 84 weeks 457 samples from 85 patients were analyzed. Patients with undetectable ctDNA at baseline had a better PFS (Hazard ratio (HR) = 0.47, median 26 weeks versus 9 weeks, p = 0.01) and OS (HR = 0.37, median not reached versus 21.3 weeks, p = 0.005) than patients with detectable ctDNA. Additionally, the HR for death was lower after the ctDNA level became undetectable during follow-up (adjusted HR: 0.16 (95{\%} CI 0.07-0.36), p-value < 0.001). ctDNA levels > 500 copies/ml at baseline or week 3 were associated with poor clinical outcome. Patients progressive exclusively in the central nervous system (CNS) had undetectable ctDNA at baseline and at subsequent assessments. In multivariate analysis adjusted for LDH, CRP, ECOG and number of metastatic sites, the ctDNA remained significant for PFS and OS. A positive correlation was observed between ctDNA levels and total metabolic tumor volume (TMTV), number of metastatic sites and total tumor burden. Conclusions: Assessment of ctDNA baseline and during therapy was predictive for tumor response and clinical outcome in metastatic melanoma patients and reflected the tumor burden. ctDNA evaluation provided reliable complementary information during anti-PD1 antibody therapy.",
keywords = "Translational research, Liquid biopsy, Circulating tumor DNA, Monitoring, Immunotherapy, Metastatic melanoma, BRAF, NRAS mutations monitoring",
author = "Teofila Seremet and Yanina Jansen and Simon Planken and Hassan Njimi and Melanie Delaunoy and {El Housni}, Hakim and Gil Awada and Schwarze, {Julia Katharina} and Marleen Keyaerts and Hendrik Everaert and Danielle Lienard and {Del Marmol}, Veronique and Pierre Heimann and Bart Neyns",
year = "2019",
month = "9",
day = "5",
doi = "10.1186/s12967-019-2051-8",
language = "English",
volume = "17",
journal = "Journal of Translational Medicine",
issn = "1479-5876",
number = "1",

}

RIS

TY - JOUR

T1 - Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy

AU - Seremet, Teofila

AU - Jansen, Yanina

AU - Planken, Simon

AU - Njimi, Hassan

AU - Delaunoy, Melanie

AU - El Housni, Hakim

AU - Awada, Gil

AU - Schwarze, Julia Katharina

AU - Keyaerts, Marleen

AU - Everaert, Hendrik

AU - Lienard, Danielle

AU - Del Marmol, Veronique

AU - Heimann, Pierre

AU - Neyns, Bart

PY - 2019/9/5

Y1 - 2019/9/5

N2 - Background: Treatment with anti-PD1 monoclonal antibodies improves the survival of metastatic melanoma patients but only a subgroup of patients benefits from durable disease control. Predictive biomarkers for durable benefit could improve the clinical management of patients. Methods: Plasma samples were collected from patients receiving anti-PD1 therapy for ctDNA quantitative assessment of BRAFV600 and NRASQ61/G12/G13 mutations. Results: After a median follow-up of 84 weeks 457 samples from 85 patients were analyzed. Patients with undetectable ctDNA at baseline had a better PFS (Hazard ratio (HR) = 0.47, median 26 weeks versus 9 weeks, p = 0.01) and OS (HR = 0.37, median not reached versus 21.3 weeks, p = 0.005) than patients with detectable ctDNA. Additionally, the HR for death was lower after the ctDNA level became undetectable during follow-up (adjusted HR: 0.16 (95% CI 0.07-0.36), p-value < 0.001). ctDNA levels > 500 copies/ml at baseline or week 3 were associated with poor clinical outcome. Patients progressive exclusively in the central nervous system (CNS) had undetectable ctDNA at baseline and at subsequent assessments. In multivariate analysis adjusted for LDH, CRP, ECOG and number of metastatic sites, the ctDNA remained significant for PFS and OS. A positive correlation was observed between ctDNA levels and total metabolic tumor volume (TMTV), number of metastatic sites and total tumor burden. Conclusions: Assessment of ctDNA baseline and during therapy was predictive for tumor response and clinical outcome in metastatic melanoma patients and reflected the tumor burden. ctDNA evaluation provided reliable complementary information during anti-PD1 antibody therapy.

AB - Background: Treatment with anti-PD1 monoclonal antibodies improves the survival of metastatic melanoma patients but only a subgroup of patients benefits from durable disease control. Predictive biomarkers for durable benefit could improve the clinical management of patients. Methods: Plasma samples were collected from patients receiving anti-PD1 therapy for ctDNA quantitative assessment of BRAFV600 and NRASQ61/G12/G13 mutations. Results: After a median follow-up of 84 weeks 457 samples from 85 patients were analyzed. Patients with undetectable ctDNA at baseline had a better PFS (Hazard ratio (HR) = 0.47, median 26 weeks versus 9 weeks, p = 0.01) and OS (HR = 0.37, median not reached versus 21.3 weeks, p = 0.005) than patients with detectable ctDNA. Additionally, the HR for death was lower after the ctDNA level became undetectable during follow-up (adjusted HR: 0.16 (95% CI 0.07-0.36), p-value < 0.001). ctDNA levels > 500 copies/ml at baseline or week 3 were associated with poor clinical outcome. Patients progressive exclusively in the central nervous system (CNS) had undetectable ctDNA at baseline and at subsequent assessments. In multivariate analysis adjusted for LDH, CRP, ECOG and number of metastatic sites, the ctDNA remained significant for PFS and OS. A positive correlation was observed between ctDNA levels and total metabolic tumor volume (TMTV), number of metastatic sites and total tumor burden. Conclusions: Assessment of ctDNA baseline and during therapy was predictive for tumor response and clinical outcome in metastatic melanoma patients and reflected the tumor burden. ctDNA evaluation provided reliable complementary information during anti-PD1 antibody therapy.

KW - Translational research

KW - Liquid biopsy

KW - Circulating tumor DNA

KW - Monitoring

KW - Immunotherapy

KW - Metastatic melanoma

KW - BRAF

KW - NRAS mutations monitoring

U2 - 10.1186/s12967-019-2051-8

DO - 10.1186/s12967-019-2051-8

M3 - Article

VL - 17

JO - Journal of Translational Medicine

JF - Journal of Translational Medicine

SN - 1479-5876

IS - 1

M1 - 303

ER -

ID: 49112943