Serum immunoglobulin G alteration tracks survival in metastatic clear cell renal cell carcinoma receiving first line immunotherapy combined with tyrosine kinase inhibitors

To assess the predictive power of serum immunoglobulin G (IgG) for outcomes in metastatic clear cell renal cell carcinoma (mccRCC) patients receiving first-line immunotherapy in combination with tyrosine kinase inhibitors (IO-TKIs) and to compare it with established biomarkers. We retrospectively analyzed 121 mccRCC patients receiving first-line IO-TKIs to assess prognostic value of serum IgG, neutrophil-to-lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), and International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk score. Univariate and multivariate Cox analyses identified the independent prognostic factors. The predictive performance of each prognostic indicator was compared using Harrell’s concordance index (C-index) and time-dependent area under the curve (AUC). At 3 months after first‑line IO‑TKIs therapy, serum IgG alteration was associated with treatment response and prognosis. IgG levels decreased in patients with partial or complete response, increased in those with progressive disease, and remained stable in those with stable disease. Patients with increased IgG had worse progression‑free survival (PFS) (HR = 3.92, P < 0.001) and overall survival (OS) (HR = 3.96, P < 0.001). Multivariate Cox analysis confirmed increased IgG as an independent prognostic factor for both worse PFS and OS. In predictive performance comparison, IgG alteration achieved a C-index of 0.71 for PFS and 0.68 for OS, with time-dependent AUCs of 0.795 (16-month PFS) and 0.68 (50-month OS), comparable or superior to IMDC, NLR, and mGPS. Serum IgG alteration provides an on-treatment risk stratification tool for mccRCC patients receiving first-line IO-TKIs. Elevated IgG at 3 months predicts poor prognosis, supporting intensified monitoring and earlier therapeutic reconsideration.