A Comprehensive Analysis of Baseline Clinical Characteristics and Biomarkers Associated with Outcome in Advanced Melanoma Patients Treated with Pembrolizumab

Gil Awada, Yanina Jansen, Julia Katharina Schwarze, Jens Tijtgat, Lennert Hellinckx, Odrade Gondry, Sim Vermeulen, Sarah Warren, Kelly Schats, Pieter-Jan van Dam, Mark Kockx, Marleen Keyaerts, Hendrik Everaert, Teofila Seremet, Anne Rogiers, Bart Neyns

Research output: Contribution to journalArticle

Abstract

BACKGROUND: Pembrolizumab improves the survival of patients with advanced melanoma. A comprehensive analysis of baseline variables that predict the benefit of pembrolizumab monotherapy has not been conducted.

METHODS: Survival data of patients with advanced melanoma who were treated with pembrolizumab in a single university hospital were collected. A multivariate Cox regression analysis was performed to correlate baseline clinical, laboratory, and radiologic characteristics and NanoString IO360 gene expression profiling (GEP) with survival.

RESULTS: 183 patients were included (stage IV 85.2%, WHO performance status ≥1 31.1%; pembrolizumab first-line 25.7%), of whom 112 underwent baseline 18F-FDG-PET/CT imaging, 58 had circulating tumor DNA (ctDNA) assessments, and GEP was available in 27 patients. Active brain metastases, a higher number of metastatic sites, lower albumin and absolute lymphocyte count (ALC), higher C-reactive protein (CRP) and neutrophil-to-lymphocyte ratio, higher total metabolic tumor volume (TMTV), and higher ctDNA levels were associated with worse survival. Elevated lactate dehydrogenase (LDH) ≥ 2ULN (upper limit of normal), CRP ≥ 10ULN, or ALC < 750/mm3 delineate a subpopulation where treatment with pembrolizumab is futile. A TMTV ≥ 80 mL encompassed 17/21 patients with LDH ≥ 2ULN, CRP ≥ 10ULN, or ALC < 750/mm3. No significant associations were observed between baseline GEP scores and survival.

CONCLUSION: Multiple baseline variables correlate with survival on pembrolizumab. TMTV is a more comprehensive baseline biomarker than CRP, LDH, or ALC in predicting the futility of pembrolizumab.

Original languageEnglish
Article number168
Pages (from-to)1-18
Number of pages18
JournalCancers
Volume13
Issue number2
DOIs
Publication statusPublished - 2 Jan 2021

Keywords

  • advanced melanoma
  • biomarkers
  • immunotherapy
  • multivariate analysis
  • pembrolizumab

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