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Sarcopenia and high NLR are associated with the development of hyperprogressive disease after second-line pembrolizumab in patients with non-small-cell lung cancer
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  • Ivan Donev,
  • Mila Petrova,
  • Maria Radanova,
  • Mariana Eneva,
  • Eleonora Dimitrova,
  • Georgi ValchevOrcid,
  • Velko Minchev,
  • Margarita Taushanova,
  • Marsella Boneva,
  • Teodora Karanikolova,
  • Radostina Gencheva,
  • Anika Ivanova,
  • Constanta Timcheva,
  • Boian Pavlov,
  • Vera Megdanova,
  • Bozhil Robev,
  • Nikolay Conev
Ivan Donev
MHAT Nadezhda
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Mila Petrova
MHAT Nadezhda
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Maria Radanova
Medical University Varna Prof Dr Paraskev Stoyanov
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Mariana Eneva
MHAT Nadezhda
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Eleonora Dimitrova
UMHAT St Marina
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Georgi Valchev
Orcid
UMHAT St Marina Varna
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Velko Minchev
University Hospital Sofiamed
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Margarita Taushanova
University Hospital Sofiamed
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Marsella Boneva
University Hospital Sofiamed
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Teodora Karanikolova
MHAT Nadezhda
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Radostina Gencheva
MHAT Nadezhda
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Anika Ivanova
MHAT Nadezhda
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Constanta Timcheva
MHAT Nadezhda
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Boian Pavlov
MHAT Nadezhda
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Vera Megdanova
University Hospital St Giovanna
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Bozhil Robev
UMHAT St Ivan Rilski
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Nikolay Conev
UMHAT St Marina
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Peer review status:UNDER REVIEW

24 Apr 2020Submitted to Clinical & Experimental Immunology
27 Apr 2020Submission Checks Completed
27 Apr 2020Assigned to Editor
11 May 2020Reviewer(s) Assigned
26 May 2020Review(s) Completed, Editorial Evaluation Pending
04 Jun 2020Editorial Decision: Revise Major
03 Jul 20201st Revision Received
03 Jul 2020Reviewer(s) Assigned
04 Jul 2020Review(s) Completed, Editorial Evaluation Pending
07 Jul 2020Editorial Decision: Revise Minor
13 Jul 20202nd Revision Received
13 Jul 2020Review(s) Completed, Editorial Evaluation Pending

Abstract

The aim of this multicenter retrospective study was to evaluate the incidence of hyperprogressive disease after treatment with pembrolizumab as a second-line treatment in patients (n=167) with non-small-cell lung cancer (NSCLC) with metastatic disease whose tumors expressed programmed death-ligand-1 in ≥1% and to search for factors associated with its development. All patients received platinum-containing chemotherapy as a first-line treatment. The neutrophil to lymphocyte ratio (NLR), platelet to lymphocyte ratio (PLR), and their derivations were retrospectively analyzed. The psoas major muscle area (PMMA) was calculated at the L3 position on computed tomography before chemotherapy and immunotherapy. Patients with ∆PMMA≥10% were considered to have sarcopenia (low muscle mass). We also performed multinomial logistic regression to estimate the effects of hematological biomarkers and ∆PMMA on the response to immunotherapy. Hyperprogressors (HPs) had significantly higher NLRs, PLRs and ∆PMMA levels than the other patients. Moreover, in multivariate regression analysis, higher levels of ∆PMMA were associated with a decreased likelihood of being a progressor (P) (OR, 0.81; 95% CI, 0.65-0.99; p=0.047) or a nonprogressor (NP) (OR, 0.76; 95% CI, 0.62-0.94; p=0.012) vs an HP. In multivariate analysis, higher NLRs tended to decrease the likelihood of being a P vs an HP (OR, 0.66; 95% CI, 0.42-1.06; p=0.09) and significantly decrease the likelihood of being an NP vs an HP (OR, 0.44; 95% CI, 0.28-0.69; p<0.0001). Our data suggest that a high pre-immunotherapy NLR and the presence of sarcopenia are potential risk factors for the development of hyperprogressive disease.