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Updated: Jun 8, 2025
A Syngeneic Mouse Model of Metastatic Renal Cell Carcinoma for Quantitative and Longitudinal Assessment of Preclinical Therapies
Published on: April 12, 2017
Dynamic Changes in Serum Immunoglobulin G Predict Clinical Response and Prognosis in Metastatic Clear-cell Renal Cell
Honglei Cui1, Jie Wu2, Gan Du1
1Department of Urology, National Cancer Center/National Clinical Research Center for Cancer/Chinese Academy of Medical Sciences and Peking Union Medical College Cancer Hospital, Beijing, China.
Background And Objective:
Systemic treatments involving immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations and TKI monotherapy have significantly improved outcomes for patients with metastatic clear-cell renal cell carcinoma (mccRCC). However, there are no biomarkers for predicting the efficacy of these treatments. Our aim was to investigate the prognostic and therapeutic significance of serum immunoglobulin G (IgG) in patients with mccRCC patients receiving systemic therapy.
Methods:
We included 318 patients with mccRCC who received TKI or IO-TKI therapy. Patients were classified into groups according to whether they had an increase or decrease in serum IgG after systemic treatment. The association between baseline serum IgG and the objective response rate (ORR) was compared between the groups using a t test. The association of the change in serum IgG with progression-free survival (PFS) and overall survival (OS) was evaluated via Cox proportional-hazards regression, and survival curves were generated using the Kaplan-Meier method.
Key Findings And Limitations:
Baseline serum IgG was not significantly associated with ORR (p = 0.055). After 3-mo systemic therapy, 133 patients (42%) exhibited an increase in serum IgG. The group with an IgG increase had significantly poorer median PFS (5.6 vs 16.2 mo; hazard ratio [HR] 3.36, 95% confidence interval [CI] 2.58-4.36; p < 0.001) and OS (26.0 vs 52.2 mo; HR 2.26, 95% CI 1.66-3.08; p < 0.001) than the group with an IgG decrease. Multivariable analysis revealed that an increase in serum IgG after 3-mo systemic therapy was an independent risk factor for both PFS (HR 3.28, 95% CI 2.51-4.30; p < 0.001) and OS (HR 1.94, 95% CI 1.41-2.68; p < 0.001). An increase in serum IgG after 1-mo treatment (n = 160) was also significantly associated with poorer median PFS (7.9 vs 13.7 mo; HR 1.62, 95% CI 1.13-2.32; p = 0.008) and OS (32.6 vs 50.5 mo; HR 1.68, 95% CI 1.09-2.59; p = 0.017).
Conclusions And Clinical Implications:
The change in serum IgG after 3-mo systemic therapy can predict the therapeutic effect and prognosis for patients with mccRCC. This predictive value was observed as early as 1 mo after treatment initiation. Our findings highlight the potential of serum IgG as a predictive biomarker in this setting. Further validation is required in large prospective studies.
Patient Summary:
We found that for patients with metastatic kidney cancer, changes in the level of an antibody called immunoglobulin G (IgG) in blood during systemic treatment can predict their overall response. Early measurement of IgG could help doctors in personalizing treatment plans and might possibly improve the effectiveness of treatment for these patients.
Insights
Increases in serum immunoglobulin G (IgG) during systemic therapy predict poorer outcomes for metastatic clear-cell renal cell carcinoma (mccRCC) patients. Early IgG monitoring may aid personalized treatment strategies.
Area of Science:
- Oncology
- Immunology
- Biomarker Discovery
Background:
- Metastatic clear-cell renal cell carcinoma (mccRCC) treatment has improved with immunotherapy-tyrosine kinase inhibitor (IO-TKI) combinations and TKI monotherapy.
- Predictive biomarkers for these systemic therapies in mccRCC are currently lacking.
- Serum immunoglobulin G (IgG) was investigated for its prognostic and therapeutic significance in mccRCC patients undergoing systemic therapy.
Purpose of the Study:
- To investigate the prognostic and therapeutic significance of serum immunoglobulin G (IgG) in patients with mccRCC receiving systemic therapy.
- To determine if changes in serum IgG levels can predict treatment efficacy and patient outcomes.
- To explore the potential of serum IgG as a predictive biomarker for mccRCC.
Main Methods:
- A cohort of 318 mccRCC patients receiving TKI or IO-TKI therapy was analyzed.
- Patients were grouped based on increases or decreases in serum IgG after systemic treatment.
- Progression-free survival (PFS) and overall survival (OS) were evaluated using Cox regression and Kaplan-Meier analysis, assessing the association of serum IgG changes with outcomes.
Main Results:
- An increase in serum IgG after 3 months of systemic therapy was associated with significantly poorer median PFS (5.6 vs 16.2 months) and OS (26.0 vs 52.2 months).
- Multivariable analysis confirmed that a serum IgG increase after 3 months was an independent risk factor for both PFS and OS.
- This predictive association was significant as early as 1 month after treatment initiation.
Conclusions:
- Changes in serum IgG levels following systemic therapy can predict therapeutic effect and prognosis in mccRCC patients.
- Serum IgG demonstrates potential as an early predictive biomarker, with significant findings observed after just one month of treatment.
- Further validation in large prospective studies is recommended to solidify serum IgG's role in guiding mccRCC treatment decisions.
