Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade
With the increasing use of immune checkpoint inhibitors (ICIs) in combination regimens and in earlier stages of advanced melanoma, the effective management of immune-related adverse events (irAEs) is key to balancing immunotherapy efficacy and toxicity. Conflicting evidence exists on possible detrim...
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Taylor & Francis Group
2025-12-01
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| Series: | OncoImmunology |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2494433 |
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| author | Nina B. Curkovic Rebecca Irlmeier Xue Bai Can Cui Fei Ye Hannah R. Burnette Aleigha R. Lawless Juliane Andrade Czapla Ryan Sullivan Douglas B. Johnson |
| author_facet | Nina B. Curkovic Rebecca Irlmeier Xue Bai Can Cui Fei Ye Hannah R. Burnette Aleigha R. Lawless Juliane Andrade Czapla Ryan Sullivan Douglas B. Johnson |
| author_sort | Nina B. Curkovic |
| collection | DOAJ |
| description | With the increasing use of immune checkpoint inhibitors (ICIs) in combination regimens and in earlier stages of advanced melanoma, the effective management of immune-related adverse events (irAEs) is key to balancing immunotherapy efficacy and toxicity. Conflicting evidence exists on possible detrimental effects of immunosuppression with corticosteroids for irAEs on ICI effectiveness. We conducted a multicenter, retrospective cohort study of immunotherapy-naïve advanced melanoma patients undergoing treatment with ipilimumab and nivolumab and a small cohort treated with nivolumab/relatlimab. We utilized univariate tests to assess response, PFS, and OS based on presence of irAE, receipt of steroids for irAEs, peak dose, and time-to-steroid, as well as multivariable analysis for response, OS, and PFS in patients receiving steroids for irAEs. Among 226 total ipilimumab/nivolumab patients, those without irAEs had poorer PFS and OS compared to irAE groups regardless of steroid administration. In subgroup analysis of patients receiving steroids for an irAE, increased time-to-steroid was significantly associated with improved response (aOR, 1.026 p = 0.0005), PFS (aHR, 0.986 p = 0.001), and OS (aHR, 0.983 p = 0.0008). Higher peak steroid dose was significantly associated with poorer PFS (aHR, 1.002 p = 0.005), and OS (aHR, 1.002 p = 0.003). Use of additional immunosuppressants was associated with poorer OS (aHR, 1.941 p = 0.018). Cumulative dose was not significantly associated with outcomes. Among 42 additional patients treated with nivolumab/relatlimab, irAEs were significantly associated with improved PFS/OS, which appeared to be slightly mitigated by steroid administration; dosing relationships were limited by small numbers. |
| format | Article |
| id | doaj-art-9e3b6bd2035b4331a4bdebe2c2cff8cc |
| institution | DOAJ |
| issn | 2162-402X |
| language | English |
| publishDate | 2025-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | OncoImmunology |
| spelling | doaj-art-9e3b6bd2035b4331a4bdebe2c2cff8cc2025-08-20T03:18:08ZengTaylor & Francis GroupOncoImmunology2162-402X2025-12-0114110.1080/2162402X.2025.2494433Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockadeNina B. Curkovic0Rebecca Irlmeier1Xue Bai2Can Cui3Fei Ye4Hannah R. Burnette5Aleigha R. Lawless6Juliane Andrade Czapla7Ryan Sullivan8Douglas B. Johnson9School of Medicine, Vanderbilt University, Nashville, TN, USAVanderbilt Ingram Cancer Center, Department of Biostatistics, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USADepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USASchool of Medicine, Vanderbilt University, Nashville, TN, USAVanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USADepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USADepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USADepartment of Medicine, Massachusetts General Hospital Cancer Center, Boston, MA, USAVanderbilt Ingram Cancer Center, Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USAWith the increasing use of immune checkpoint inhibitors (ICIs) in combination regimens and in earlier stages of advanced melanoma, the effective management of immune-related adverse events (irAEs) is key to balancing immunotherapy efficacy and toxicity. Conflicting evidence exists on possible detrimental effects of immunosuppression with corticosteroids for irAEs on ICI effectiveness. We conducted a multicenter, retrospective cohort study of immunotherapy-naïve advanced melanoma patients undergoing treatment with ipilimumab and nivolumab and a small cohort treated with nivolumab/relatlimab. We utilized univariate tests to assess response, PFS, and OS based on presence of irAE, receipt of steroids for irAEs, peak dose, and time-to-steroid, as well as multivariable analysis for response, OS, and PFS in patients receiving steroids for irAEs. Among 226 total ipilimumab/nivolumab patients, those without irAEs had poorer PFS and OS compared to irAE groups regardless of steroid administration. In subgroup analysis of patients receiving steroids for an irAE, increased time-to-steroid was significantly associated with improved response (aOR, 1.026 p = 0.0005), PFS (aHR, 0.986 p = 0.001), and OS (aHR, 0.983 p = 0.0008). Higher peak steroid dose was significantly associated with poorer PFS (aHR, 1.002 p = 0.005), and OS (aHR, 1.002 p = 0.003). Use of additional immunosuppressants was associated with poorer OS (aHR, 1.941 p = 0.018). Cumulative dose was not significantly associated with outcomes. Among 42 additional patients treated with nivolumab/relatlimab, irAEs were significantly associated with improved PFS/OS, which appeared to be slightly mitigated by steroid administration; dosing relationships were limited by small numbers.https://www.tandfonline.com/doi/10.1080/2162402X.2025.2494433Immune checkpoint inhibitorimmune-related adverse event - irAEimmunosuppressionimmunotherapy |
| spellingShingle | Nina B. Curkovic Rebecca Irlmeier Xue Bai Can Cui Fei Ye Hannah R. Burnette Aleigha R. Lawless Juliane Andrade Czapla Ryan Sullivan Douglas B. Johnson Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade OncoImmunology Immune checkpoint inhibitor immune-related adverse event - irAE immunosuppression immunotherapy |
| title | Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade |
| title_full | Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade |
| title_fullStr | Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade |
| title_full_unstemmed | Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade |
| title_short | Impact of steroid dose and timing on efficacy of combination PD-1/CTLA-4 blockade |
| title_sort | impact of steroid dose and timing on efficacy of combination pd 1 ctla 4 blockade |
| topic | Immune checkpoint inhibitor immune-related adverse event - irAE immunosuppression immunotherapy |
| url | https://www.tandfonline.com/doi/10.1080/2162402X.2025.2494433 |
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