Serum IgG: A novel biomarker for efficacy and prognosis in metastatic clear cell renal cell carcinoma patients receiving first-line immunotherapy combined with tyrosine kinase inhibitors.

Abstract

445 Background: The first-line use of immunotherapy in combination with tyrosine kinase inhibitors (IO-TKIs) significantly improves the overall prognosis of patients with metastatic clear cell renal cell carcinoma (mccRCC). Nevertheless, clinically applicable biomarkers for predicting the prognosis and efficacy of first-line IO-TKIs therapy remain elusive. Methods: We retrospectively evaluated 121 mccRCC patients treated with first-line IO-TKIs to assess the prognostic value of serum immunoglobulin G (IgG), neutrophil-to-lymphocyte ratio (NLR), modified Glasgow prognostic score (mGPS), their 3-month dynamic changes, and the International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) risk group. The Kaplan-Meier survival curves were drawn to show the differences in progression-free survival (PFS) and overall survival (OS) among various clinical subgroups. Univariate and multivariate COX analyses were used to identify the independent prognostic factors. The time-dependent ROC curves were plotted to compare the ability of each model to predict specific PFS and OS time points. Results: At a median follow-up of 31 months for the cohort (median age 60 years), the objective response rate was 63.64%. The median PFS was 18 months; however, the median OS was not reached. Baseline IgG levels were comparable across the partial response (PR)/complete response (CR), stable disease (SD), and progressive disease (PD) groups (P = 0.160). Following 3 months of treatment, PR/CR group experienced a significant decline in IgG (P < 0.001), SD group showed stable levels (P = 0.235), and PD group demonstrated a significant elevation (P < 0.001). Elevated serum IgG after 3 months of treatment was associated with worse PFS (HR = 3.92, P < 0.001) and OS (HR = 3.96, P < 0.001). High IMDC score, high baseline mGPS, and baseline NLR (≥3) predicted poorer PFS and OS. Multivariate COX analysis showed that IgG alteration and baseline mGPS were independent prognostic factors for PFS and OS in mccRCC patients receiving first-line IO-TKIs. At 16 months of PFS, IgG alteration (AUC = 0.795) exhibited superior performance compared to other predictors (baseline mGPS: AUC = 0.679, baseline NLR: AUC = 0.694, IMDC: AUC = 0.651). At 50 months of OS, IgG alteration (AUC = 0.680) demonstrated non-inferior predictive capability compared to other indicators (baseline mGPS: AUC = 0.747, baseline NLR: AUC = 0.673, IMDC: AUC = 0.574). Conclusions: Serum IgG alterations emerge as a superior independent prognostic biomarker in mccRCC patients receiving first-line IO-TKIs.