Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors

Murtaza Ahmed, Mitchell S. Von Itzstein, Thomas Sheffield, Shaheen Khan, Farjana Fattah, Jason Y. Park, Vinita Popat, Jessica M. Saltarski, Yvonne Gloria-Mccutchen, David Hsiehchen, Jared Ostmeyer, Saad A. Khan, Nazima Sultana, Yang Xie, Quan Zhen Li, Edward K. Wakeland, David E. Gerber

Research output: Contribution to journalArticlepeer-review

Abstract

Background Increased body mass index (BMI) has been associated with improved response to immune checkpoint inhibitors (ICIs) in multiple cancer types. We evaluated associations between BMI, ICI dosing strategy, and clinical outcomes. Methods We abstracted clinical data on patients with cancer treated with ICI, including age, sex, cancer type, BMI, ICI type, dosing strategy (weight-based or fixed), radiographic response, overall survival (OS), and progression-free survival (PFS). We compared clinical outcomes between low-BMI and high-BMI populations using Kaplan-Meier curves, Cox regressions, and Pearson product-moment correlation coefficients. Results A total of 297 patients were enrolled, of whom 40% were women and 59% were overweight (BMI≥25). Of these, 204 (69%) received fixed and 93 (31%) received weight-based ICI dosing. In the overall cohort, overweight BMI was associated with improved PFS (HR 0.69; 95% CI 0.51 to 0.94; p=0.02) and had a trend toward improved OS (HR 0.77; 95% CI 0.57 to 1.04; p=0.08). For both endpoints, improved outcomes in the overweight population were limited to patients who received weight-based ICI dosing (PFS HR 0.53; p=0.04 for weight-based; vs HR 0.79; p=0.2 for fixed dosing) (OS HR 0.56; p=0.03 for weight-based; vs HR 0.89; p=0.54 for fixed dosing). In multivariable analysis, BMI was not associated with PFS or OS. However, the interaction of BMI25 and weight-based dosing had a trend toward association with PFS (HR 0.53; 95% CI 0.26 to 1.10; p=0.09) and was associated with OS (HR 0.50; 95% CI 0.25 to 0.99; p=0.05). Patients with BMI25 tended to have better outcomes with fixed-dose compared with weight-based ICI, while patients with BMI≥25 tended to have better outcomes with weight-based ICI, although these differences did not achieve statistical significance. There was no association between radiographic response and BMI with fixed-dose ICI (p=0.97), but a near-significant trend with weight-based ICI (p=0.1). In subset analyses, the association between BMI, ICI dosing strategy, and clinical outcomes appeared limited to men. Conclusions The clinical benefit of ICI in high-BMI populations appears limited to individuals receiving weight-based ICI dosing. Further research into optimal ICI dosing strategies may be warranted.

Original languageEnglish (US)
Article numbere002349
JournalJournal for ImmunoTherapy of Cancer
Volume9
Issue number6
DOIs
StatePublished - Jun 14 2021

Keywords

  • Th1-Th2 balance
  • immunotherapy
  • obesity
  • programmed cell death 1 receptor
  • tumor
  • tumor microenvironment

ASJC Scopus subject areas

  • Immunology and Allergy
  • Immunology
  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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