Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors
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...
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BMJ Publishing Group
2021-06-01
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| Series: | Journal for ImmunoTherapy of Cancer |
| Online Access: | https://jitc.bmj.com/content/9/6/e002349.full |
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| author | Yang Xie Vinita Popat Shaheen Khan Saad A Khan Edward K Wakeland Quan-Zhen Li Murtaza Ahmed Mitchell S von Itzstein Thomas Sheffield Farjana Fattah Jason Y Park Jessica M Saltarski Yvonne Gloria-McCutchen David Hsiehchen Jared Ostmeyer Nazima Sultana David E Gerber |
| author_facet | Yang Xie Vinita Popat Shaheen Khan Saad A Khan Edward K Wakeland Quan-Zhen Li Murtaza Ahmed Mitchell S von Itzstein Thomas Sheffield Farjana Fattah Jason Y Park Jessica M Saltarski Yvonne Gloria-McCutchen David Hsiehchen Jared Ostmeyer Nazima Sultana David E Gerber |
| author_sort | Yang Xie |
| collection | DOAJ |
| description | 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 BMI<25 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. |
| format | Article |
| id | doaj-art-621df1a1a67640a2af6757144a9d4c70 |
| institution | Kabale University |
| issn | 2051-1426 |
| language | English |
| publishDate | 2021-06-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | Journal for ImmunoTherapy of Cancer |
| spelling | doaj-art-621df1a1a67640a2af6757144a9d4c702024-11-08T18:45:08ZengBMJ Publishing GroupJournal for ImmunoTherapy of Cancer2051-14262021-06-019610.1136/jitc-2021-002349Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitorsYang Xie0Vinita Popat1Shaheen Khan2Saad A Khan3Edward K Wakeland4Quan-Zhen Li5Murtaza Ahmed6Mitchell S von Itzstein7Thomas Sheffield8Farjana Fattah9Jason Y Park10Jessica M Saltarski11Yvonne Gloria-McCutchen12David Hsiehchen13Jared Ostmeyer14Nazima Sultana15David E Gerber162 Department of Respiratory Diseases, The First Affiliated Hospital of Henan University of Chinese Medicine, Zhengzhou, China1 School of Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USADepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA2 Department of Internal Medicine (Division of Hematology-Oncology), The University of Texas Southwestern Medical Center, Dallas, Texas, USADepartment of Immunology, University of Texas Southwestern Medical Center, Dallas, Texas, USA1Department of Immunology, UT Southwestern Medical Center, Dallas, TX USA1 School of Medicine, The University of Texas Southwestern Medical Center, Dallas, Texas, USADivision of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA3 Department of Population and Data Sciences, The University of Texas Southwestern Medical Center, Dallas, Texas, USAHarold C Simmons Comprehensive Cancer Center, University of Texas Southwestern Medical Center, Dallas, Texas, USADepartment of Pathology, University of Texas Southwestern Medical Center, Dallas, Texas, USA5 Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USA5 Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USADepartment of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USA3 Department of Population and Data Sciences, The University of Texas Southwestern Medical Center, Dallas, Texas, USA5 Harold C. Simmons Comprehensive Cancer Center, The University of Texas Southwestern Medical Center, Dallas, Texas, USADivision of Hematology and Oncology, Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, Texas, USABackground 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 BMI<25 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.https://jitc.bmj.com/content/9/6/e002349.full |
| spellingShingle | Yang Xie Vinita Popat Shaheen Khan Saad A Khan Edward K Wakeland Quan-Zhen Li Murtaza Ahmed Mitchell S von Itzstein Thomas Sheffield Farjana Fattah Jason Y Park Jessica M Saltarski Yvonne Gloria-McCutchen David Hsiehchen Jared Ostmeyer Nazima Sultana David E Gerber Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors Journal for ImmunoTherapy of Cancer |
| title | Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors |
| title_full | Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors |
| title_fullStr | Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors |
| title_full_unstemmed | Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors |
| title_short | Association between body mass index, dosing strategy, and efficacy of immune checkpoint inhibitors |
| title_sort | association between body mass index dosing strategy and efficacy of immune checkpoint inhibitors |
| url | https://jitc.bmj.com/content/9/6/e002349.full |
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