Body mass index, adiposity and tumour infiltrating lymphocytes as prognostic biomarkers in patients treated with immunotherapy: A multi-parametric analysis

Eur J Cancer. 2021 Mar:145:197-209. doi: 10.1016/j.ejca.2020.12.028. Epub 2021 Jan 22.

Abstract

Background: We performed a multi-parametric analysis investigating the association between adiposity (as measured using body mass index [BMI] and computed tomography [CT]-based body composition), tumour infiltrating lymphocytes (TILs) and clinical outcomes in patients with advanced-stage cancer treated with immunotherapy in phase I clinical trials.

Material and methods: All consecutive patients (N = 153) with metastatic solid tumours treated within immunotherapy-based phase I clinical trials between August 2014 and May 2019 at our institution were included. Baseline characteristics, BMI, TILs value and CT-assessed fat indices (total fat area [TFA], subcutaneous fat area [SFA] and visceral fat [VFA]) were collected. The primary endpoints were to evaluate the impact of these parameters on overall survival (OS) and progression-free survival (PFS). Kaplan-Meier method and Cox proportional-hazards model were used for survival analyses.

Results: At both univariate and multivariate analyses, BMI was not associated with PFS neither when considered as continuous variable (HR 0.90, 95% CI 0.74-1.09, P = 0.28) nor as dichotomous variable (underweight/normal versus overweight/obese) (HR 0.79, 95% CI 0.55-1.14, P = 0.21). Interestingly, patients diagnosed with 'immunogenic' tumours and higher VFA/SFA ratio (1st and 2nd tertile versus 3rd tertile) presented an increased OS (HR 0.88, 95% CI 0.78-1.00, P = 0.047).

Conclusion: Our analysis showed that patients with tumours that are already known as responsive to ICIs with higher VFA/SFA ratio presented an increased OS. Further studies are needed to elucidate the effect of adiposity on the host immune response to immunotherapy.

Keywords: Biomarkers; Body composition; Body mass index; Immune checkpoint inhibitors; Immunotherapy; Phase I; Solid tumours.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity*
  • Adult
  • Aged
  • Aged, 80 and over
  • Body Mass Index*
  • Clinical Trials, Phase I as Topic
  • Female
  • Humans
  • Immunotherapy* / adverse effects
  • Lymphocytes, Tumor-Infiltrating / immunology*
  • Male
  • Middle Aged
  • Neoplasm Metastasis
  • Neoplasms / immunology
  • Neoplasms / mortality
  • Neoplasms / pathology
  • Neoplasms / therapy*
  • Obesity / diagnosis*
  • Obesity / mortality
  • Obesity / physiopathology
  • Progression-Free Survival
  • Retrospective Studies
  • Risk Assessment
  • Risk Factors
  • Time Factors
  • Tumor Microenvironment