Baseline and Dynamic Changes in Hemoglobin Levels Predict Treatment Response and Prognosis in Metastatic Renal Cell Carcinoma: A Multicenter Retrospective Study

In this retrospective cohort study of 276 patients with metastatic renal cell carcinoma (mRCC), we demonstrate that higher hemoglobin (Hb) levels prior to, and increases in Hb during systemic therapy predict better outcomes across three established frontline treatments. This study identifies Hb as a promising clinical marker of treatment outcomes in mRCC, of which there have been few to date. Introduction: Clinical markers of response in metastatic renal cell carcinoma (mRCC) are lacking. Low hemoglobin (Hb) is associated with poor outcomes in the IMDC risk score. This study evaluates the role of Hb as a marker of treatment outcomes in mRCC. Patients and Methods: This multicenter retrospective study evaluated 276 patients with mRCC treated with frontline immune checkpoint inhibitor (ICI) therapy, ICI and vascular endothelial growth factor (VEGF) inhibitor (VEGFI) combinations (ICI/VEGFI), or VEGFI monotherapy between 2014 and 2021. Hb levels at baseline, week 6 and 12 and at disease progression or death were recorded. Patients were categorized as responders (CR + PR) or nonresponders (SD + PD) using cross-sectional imaging at week 12. The association between baseline and dynamic changes in Hb and oncological outcomes was assessed. Results: Thirty-seven percent, 40% and 22% of patients received ICIs, ICI/VEGFI and VEGFI respectively. In patients receiving ICIs, there was a significant increase in Hb amongst responders from baseline to week 12 ( P = .02). Amongst patients receiving ICI/VEGFI, there was an increase in Hb from baseline to week 12 which was greater in responders ( P < .001). In patients receiving VEGFI monotherapy, responders had a higher Hb at baseline ( P = .01), week 6 ( P = .04), and week 12 ( P = .003). An increase in Hb was a significant independent predictor of progression-free survival amongst patients receiving ICIs (HR 0.40, 95%CI, 0.19-0.83, P = .009). Conclusion: Baseline and dynamic changes in Hb are associated with first-line treatment outcomes in patients with mRCC and represent a pragmatic early serological marker.