TY - JOUR
T1 - Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors
AU - Ahmed, Murtaza
AU - Von Itzstein, Mitchell S.
AU - Sheffield, Thomas
AU - Khan, Shaheen
AU - Fattah, Farjana
AU - Park, Jason Y.
AU - Popat, Vinita
AU - Saltarski, Jessica M.
AU - Gloria-Mccutchen, Yvonne
AU - Hsiehchen, David
AU - Ostmeyer, Jared
AU - Khan, Saad
AU - Sultana, Nazima
AU - Xie, Yang
AU - Li, Quan-zhen
AU - Wakeland, Edward K.
AU - Gerber, David E.
N1 - Funding Information:
Funding Funded in part by a National Cancer Institute Midcareer Investigator Award in Patient-Oriented Research (K24 CA201543-01; to DEG), the National Institute of Allergy and Infectious Disease (1U01AI156189-01; to DEG, EKW, YX), an American Cancer Society-Melanoma Research Alliance Team Award (MRAT-18-114-01-LIB; to DEG), a V Foundation Robin Roberts Cancer Survivorship Award (DT2019-007; to DEG), the University of Texas Lung Cancer Specialized Program of Research Excellence (SPORE) (P50CA070907-21), and the Harold C. Simmons Comprehensive Cancer Center Data Sciences Shared Resource (1P30 CA 142543-03).
Publisher Copyright:
© 2021 EDP Sciences. All rights reserved.
PY - 2021/6/14
Y1 - 2021/6/14
N2 - 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.
AB - 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.
KW - Th1-Th2 balance
KW - immunotherapy
KW - obesity
KW - programmed cell death 1 receptor
KW - tumor
KW - tumor microenvironment
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U2 - 10.1136/jitc-2021-002349
DO - 10.1136/jitc-2021-002349
M3 - Article
C2 - 34127546
AN - SCOPUS:85108165464
SN - 2051-1426
VL - 9
JO - Journal for ImmunoTherapy of Cancer
JF - Journal for ImmunoTherapy of Cancer
IS - 6
M1 - e002349
ER -