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

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

Publication date: Sep 05, 2019

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.

Plasma samples were collected from patients receiving anti-PD1 therapy for ctDNA quantitative assessment of BRAF and NRAS mutations.

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  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.

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.

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Seremet, T., Jansen, Y., Planken, S., Njimi, H., Delaunoy, M., El Housni, H., Awada, G., Schwarze, J.K., Keyaerts, M., Everaert, H., Lienard, D., Marmol, Del, Heimann, P., and Neyns, B. Undetectable circulating tumor DNA (ctDNA) levels correlate with favorable outcome in metastatic melanoma patients treated with anti-PD1 therapy. 24029. 2019 J Transl Med (17):1.

Concepts Keywords
Biomarkers Survival metastatic melanoma
BRAF Tumor
Central Nervous System Antibody therapy
Correlation Immunotherapy
LDH Medicine
Melanoma Clinical medicine
Metastatic Branches of biology
Monoclonal Antibodies DNA
Multivariate Cancer
Progressive Anatomical pathology
Subgroup Circulating tumor DNA
Tumor Neoplasms
Liquid biopsy
Biomarker
Melanoma
BRAF
Antibodies

Semantics

Type Source Name
pathway BSID Small cell lung cancer
disease MESH small cell lung cancer
drug DRUGBANK Guanosine
gene UNIPROT TSPAN33
gene UNIPROT ERBB2
gene UNIPROT PAEP
drug DRUGBANK Polyethylene glycol
disease MESH diagnosis
gene UNIPROT LIAS
gene UNIPROT WDR48
gene UNIPROT IL1R1
gene UNIPROT RBM15
gene UNIPROT TIE1
gene UNIPROT IL4I1
drug DRUGBANK Ibuprofen
gene UNIPROT CXCL2
gene UNIPROT EXOG
gene UNIPROT TNIP1
disease DOID Cancer
gene UNIPROT ENPEP
gene UNIPROT RPL22
gene UNIPROT AHR
drug DRUGBANK L-Threonine
drug DRUGBANK Serine
gene UNIPROT RAF1
gene UNIPROT ZHX2
drug DRUGBANK Nevirapine
gene UNIPROT CYREN
gene UNIPROT ARR3
gene UNIPROT CXADR
gene UNIPROT CASR
gene UNIPROT NR1I3
gene UNIPROT SPG7
disease MESH carcinomatosis
gene UNIPROT CSF2
disease MESH emergency
gene UNIPROT SET
gene UNIPROT PSD4
disease MESH tic
gene UNIPROT EGFR
disease MESH relapse
gene UNIPROT MAX
gene UNIPROT CTLA4
gene UNIPROT NR1H4
gene UNIPROT BFAR
gene UNIPROT RAB8A
drug DRUGBANK Honey
gene UNIPROT IK
gene UNIPROT MAP6
gene UNIPROT MRLN
gene UNIPROT MLN
drug DRUGBANK Trametinib
gene UNIPROT BID
drug DRUGBANK Dabrafenib
gene UNIPROT MUC1
drug DRUGBANK Coenzyme M
disease MESH dif
drug DRUGBANK Indoleacetic acid
gene UNIPROT CARD16
drug DRUGBANK Creatinolfosfate
gene UNIPROT FURIN
gene UNIPROT SULT2A1
gene UNIPROT PDGFB
gene UNIPROT BPIFA4P
gene UNIPROT DEPP1
drug DRUGBANK Stavudine
gene UNIPROT PELI1
disease MESH metastasis
gene UNIPROT MTSS1
gene UNIPROT CPOX
gene UNIPROT TNFRSF11A
disease DOID BOR
gene UNIPROT RRAD
gene UNIPROT KIT
gene UNIPROT TALDO1
gene UNIPROT LRSAM1
gene UNIPROT TNFSF13
gene UNIPROT ANP32B
pathway BSID Colorectal cancer
disease DOID colorectal cancer
disease MESH colorectal cancer
disease DOID uveal melanoma
disease MESH uveal melanoma
disease DOID lung cancer
disease MESH lung cancer
disease DOID ers
pathway BSID Immune System
drug DRUGBANK Pembrolizumab
drug DRUGBANK Nivolumab
drug DRUGBANK Ipilimumab
gene UNIPROT MS4A2
gene UNIPROT GOPC
pathway BSID Reproduction
gene UNIPROT ATF6B
gene UNIPROT MENT
drug DRUGBANK Trestolone
gene UNIPROT ARL2BP
gene UNIPROT BSND
gene UNIPROT SCN8A
gene UNIPROT CSRP1
gene UNIPROT CRP
disease MESH death
drug DRUGBANK Tropicamide
gene UNIPROT NRAS
gene UNIPROT BRAF
gene UNIPROT PDCD1
gene UNIPROT SPATA2
pathway BSID Melanoma
disease DOID melanoma
disease MESH melanoma
disease MESH tumor

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