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. 2021 Jan 6;13(2):168.
doi: 10.3390/cancers13020168.

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

Gil Awada  1 , Yanina Jansen  2 , Julia Katharina Schwarze  1 , Jens Tijtgat  1 , Lennert Hellinckx  1 , Odrade Gondry  3 , Sim Vermeulen  3 , Sarah Warren  4 , Kelly Schats  5 , Pieter-Jan van Dam  5 , Mark Kockx  5 , Marleen Keyaerts  3 , Hendrik Everaert  3 , Teofila Seremet  1 , Anne Rogiers  6 , Bart Neyns  1
Affiliations

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

Gil Awada et al. Cancers (Basel). .

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.

Keywords: advanced melanoma; biomarkers; immunotherapy; multivariate analysis; pembrolizumab.

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Conflict of interest statement

Gil Awada: consulting or advisory role—Novartis; speaker’s bureau—Novartis; research funding—Novartis (institutional), Pfizer (institutional); travel, accommodation, and expenses—Astellas Pharma, MSD Oncology, Novartis, Pfizer. Yanina Jansen: travel, accommodation, and expenses—Bristol-Myers Squibb, MSD, Pfizer. Julia Katharina Schwarze: travel, accommodation, and expenses—MSD, Amgen. Sarah Warren: employment—NanoString Technologies; stock and other ownership interests: NanoString Technologies. Kelly Schats: employment—HistoGeneX. Pieter-Jan van Dam: employment—HistoGeneX. Mark Kockx: employment—HistoGeneX; leadership—HistoGeneX; stock and other ownership—HistoGeneX; consulting or advisory role—AstraZeneca, Roche, Ventana Medical Systems; travel, accommodation, and expenses—AstraZeneca, Roche, Ventana Medical Systems. Marleen Keyaerts: research funding—senior clinical investigator mandate by Research Foundation—Flanders (FWO), Precirix (institutional); patents, royalties, other intellectual property—Vrije Universiteit Brussel (institutional). Teofila Seremet: employment—Johnson & Johnson (family member); consulting or advisory role—Novartis; speaker’s bureau—Novartis; travel, accommodation, expenses—GlaxoSmithKline, MSD, Novartis. Anne Rogiers: honoraria—Janssen-Cilag, Bristol-Myers Squibb, MSD. Bart Neyns: honoraria—Roche, Bristol-Myers Squibb, MSD, Novartis, AstraZeneca; consulting or advisory role—Amgen, Bristol-Myers Squibb, MSD, Novartis, Pfizer/EMD Serono, Roche, Sanofi; speaker’s bureau—Novartis; research funding—Merck, Novartis, Pfizer, Stichting tegen Kanker, Kom op tegen Kanker, Fonds voor Wetenschappelijk Onderzoek; travel, accommodation, expenses—Amgen, Bristol-Myers Squibb, MSD, Novartis, Roche. All other authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Progression-free and overall survival in subgroups of patients with LDH ≥ 2ULN (panels A,B), CRP ≥ 10ULN (panels C,D), and ALC < 750/mm3 (panels E,F) in the total study population. Abbreviations: ALC—absolute lymphocyte count; CRP—C-reactive protein; LDH—lactate dehydrogenase; ULN—upper limit of normal.
Figure 2
Figure 2
Venn diagram depicting overlap in the number of patients between the categories of LDH ≥ 2ULN (n = 18), CRP ≥ 10ULN (n = 14) and ALC < 750/mm3 (n = 13). Abbreviations: ALC—absolute lymphocyte count; CRP—C-reactive protein; LDH—lactate dehydrogenase; ULN—upper limit of normal.
Figure 3
Figure 3
Venn diagram depicting overlap in number of patients between the categories of LDH ≥ 2ULN (n = 5), CRP ≥ 10ULN (n = 3), ALC < 750/mm3 (n = 7), and TMTV ≥ 80 mL (n = 17). Abbreviations: ALC—absolute lymphocyte count; CRP—C-reactive protein; LDH—lactate dehydrogenase; TMTV—total metabolic tumor volume; ULN—upper limit of normal.
See this image and copyright information in PMC

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