Trial reportJournal for immunotherapy of cancer2019
Tumor mutation burden and circulating tumor DNA in combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma - results of a prospective biomarker study.
Trial report in Journal for immunotherapy of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05644457 (Exploratory Study of Early Biomarkers Allowing Dynamic Assessment of Response to Treatment in Cancers of the Head and Neck), which is not on this map. Cited by 122 papers, 4 of them syntheses that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Exploratory Study of Early Biomarkers Allowing Dynamic Assessment of Response to Treatment in Cancers of the Head and Neck
Who cites it
122 citing papers in PubMed, 4 syntheses or guidelines pooled it, 209 citations in OpenAlex.
- Plasma ctDNA kinetics as a predictor of systemic therapy response for advanced non-small cell lung cancer: a systematic review and meta-analysis.The oncologist · 2025Pooled it
- Role of Surgery in Metastatic Melanoma and Review of Melanoma Molecular Characteristics.Cells · 2024Pooled it
- The prognostic value of circulating tumor DNA in malignant melanoma patients treated with immune checkpoint inhibitors: a systematic review and meta-analysis.Frontiers in immunology · 2024Pooled it
- Integrated genomic analysis identifies a genetic mutation model predicting response to immune checkpoint inhibitors in melanoma.Cancer medicine · 2020Pooled it
- Bempegaldesleukin Plus Nivolumab in First-Line Metastatic Melanoma.Journal of clinical oncology : official journal of the American Society of Clinical Oncology · 2021Trial
- Recent advances in the molecular genetic mechanisms and immune microenvironment of uveal melanoma.Melanoma research · 2026Review
- Overcoming tumour resistance in cancer immunotherapy through predictive and pharmacodynamic biomarkers.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Clinical, Dermatoscopic, Histological and Molecular Prognostic and Predictive Factors of Metastatic Melanoma Response to Immunotherapy: A Systematic Review and Drug Class Meta-Analysis.Journal of clinical medicine · 2026Review
- Oncofetal chondroitin sulfate positive circulating tumor cells as prognostic biomarkers in early-stage melanoma.Scientific reports · 2026Article
- Proteogenomic detection of tumor-specific somatic mutant proteins in urinary extracellular vesicles for non-invasive monitoring of bladder cancer.Frontiers in oncology · 2026Article
- A combination of low TMB and PD-L1 expression predict poor progression-free survival of metastatic melanoma patients treated with first-line ipilimumab plus nivolumab.Frontiers in immunology · 2026Article
- Research hotspots and trends of immunotherapy and melanoma: A bibliometric analysis during 2014-2024.Human vaccines & immunotherapeutics · 2025Article
- Personalized Circulating Tumor DNA Assay to Assess Long-Term Clinical Benefit in Patients with Advanced Melanoma.Cancers · 2025Article
- Circulating tumor DNA monitoring in advanced mutated melanoma (LIQUID-MEL).The journal of liquid biopsy · 2025Article
- Mechanisms of Resistance to Anti-PD-1 Immunotherapy in Melanoma and Strategies to Overcome It.Biomolecules · 2025Review
- Detection of Circulating Tumor DNA in Liquid Biopsy: Current Techniques and Potential Applications in Melanoma.International journal of molecular sciences · 2025Review
- Immunotherapy of Human Melanoma: Past, Present, Future.Current medicinal chemistry · 2025Review
- Adjuvant anti-PD-1 therapy improves melanoma-specific survival in stage IIIC-IV melanoma patients with high tumor mutation burden andFrontiers in oncology · 2025Article
- Strategies to Overcome PD-1/PD-L1 Blockade Resistance: Focusing on Combination with Immune Checkpoint Blockades.Journal of Cancer · 2025Review
- CTLA-4 and PD-1 combined blockade therapy for malignant melanoma brain metastases: mechanisms, challenges, and prospects.Frontiers in immunology · 2025Review
62 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
18 authors at 6 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMetastasized or unresectable melanoma has been the first malignant tumor to be successfully treated with checkpoint inhibitors. Nevertheless, about 40-50% of the patients do not respond to these treatments and severe side effects are observed in up to 60%. Therefore, there is a high need to identify reliable biomarkers predicting response. Tumor Mutation Burden (TMB) is a debated predictor for response to checkpoint inhibitors and early measurement of ctDNA can help to detect treatment failure to immunotherapy in selected melanoma patients. However, it has not yet been clarified how TMB and ctDNA can be used to estimate response to combined CTLA-4 and PD-1 antibody therapy in metastatic melanoma. PATIENTS AND
methodsIn this prospective biomarker study, we included 35 melanoma patients with ipilimumab (anti-CTLA-4) and nivolumab (anti-PD-1) therapy. In all patients, a tumor panel of 710 tumor-associated genes was applied (tumor vs. reference tissue comparison), followed by repetitive liquid biopsies. Cell-free DNA was extracted and at least one driver mutation was monitored. Treatment response was evaluated after about three months of therapy.
resultsTMB was significantly higher in responders than in nonresponders and TMB > 23.1 Mut/Mb (TMB-high) was associated with a survival benefit compared to TMB ≤ 23.1 Mut/Mb (TMB-low or TMB-intermediate). Furthermore, a > 50% decrease of cell-free DNA concentration or undetectable circulating tumor DNA (ctDNA), measured by tumor-specific variant copies/ml of plasma at first follow-up three weeks after treatment initiation were significantly associated with response to combined immunotherapy and improved overall survival, respectively. It is noticeable that no patient with TMB ≤ 23.1 Mut/Mb and detectable or increasing ctDNA at first follow-up responded to immunotherapy.
conclusionHigh TMB, > 50% decrease of cell-free DNA concentration, and undetectable ctDNA at first follow-up seem to be associated with response and overall survival under combined immunotherapy. The evaluation of ctDNA and cell-free DNA three weeks after treatment initiation may be suitable for early assessment of efficacy of immunotherapy.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.