Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors
Open Access
- 14 June 2021
- journal article
- research article
- Published by BMJ in Journal for ImmunoTherapy of Cancer
- Vol. 9 (6), e002349
- https://doi.org/10.1136/jitc-2021-002349
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 BMI≥25 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 BMIConclusions 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.Keywords
Funding Information
- V Foundation Robin Roberts Cancer Survivorship Award (DT2019-007)
- National Institute of Allergy and Infectious Disease (1U01AI156189-01)
- Harold C. Simmons Comprehensive Cancer Center Data Sciences Shared Resource (1P30 CA 142543-03)
- University of Texas Lung Cancer Specialized Program of Research Excellence (P50CA070907-21)
- National Cancer Institute (K24 CA201543-01)
- American Cancer Society-Melanoma Research Alliance Team Award (MRAT-18-114-01-LIB)
This publication has 48 references indexed in Scilit:
- Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trialThe Lancet, 2015
- Pembrolizumab for the Treatment of Non–Small-Cell Lung CancerThe New England Journal of Medicine, 2015
- Mutational landscape determines sensitivity to PD-1 blockade in non–small cell lung cancerScience, 2015
- Adiposity induces lethal cytokine storm after systemic administration of stimulatory immunotherapy regimens in aged miceThe Journal of Experimental Medicine, 2014
- An Epidemiologic and Genomic Investigation Into the Obesity Paradox in Renal Cell CarcinomaJNCI Journal of the National Cancer Institute, 2013
- The weight of nations: an estimation of adult human biomassBMC Public Health, 2012
- New response evaluation criteria in solid tumours: Revised RECIST guideline (version 1.1)European Journal of Cancer, 2009
- Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studiesThe Lancet, 2008
- Mechanisms of Intravenous Immunoglobulin Action in Immune Thrombocytopenic PurpuraHuman Immunology, 2005
- Glutamine requirements in the generation of lymphokine-activated killer cellsClinical Nutrition, 1994