Prognostic Significance of Increases in Hemoglobin in Renal Cell Carcinoma Patients During Treatment With VEGF-directed Therapy

Background Increases in hemoglobin have been reported in renal cell carcinoma (RCC) patients treated with vascular endothelial growth factor (VEGF) pathway–targeted therapies and have been associated with increased progression-free survival (PFS). We retrospectively evaluated its significance as a predictive biomarker of clinical response in RCC. Patients and Methods Patients with advanced RCC treated with VEGF receptor tyrosine kinase inhibitors (TKIs) or bevacizumab as a first-line therapy were identified. Hemoglobin levels were retrieved at baseline and then at monthly intervals for 6 months. Absolute and percentage increases over baseline were evaluated as predictors of objective response rate, PFS, time to treatment failure, and overall survival. Cox regression was used to estimate change status hazard ratios (HR) in univariate and multivariable models. Results Among the 71 eligible patients, elevations in hemoglobin were observed in 83%, with a median time to increase of 2.4 weeks since treatment initiation. Changes in hemoglobin at time of response were not associated with objective response rate. Landmark analysis at 3 months showed that increases in hemoglobin were associated with worse PFS (8.0 vs. 19.4 months; HR = 2.29; 95% confidence interval, 1.01-5.16; P = .05) and time to treatment failure (6.4 vs. 18.1 months; HR = 2.14; 95% confidence interval, 0.99-4.60, P = .05). Patients with greater increases (15% or more) had significantly shorter PFS (5.5 vs. 13.6 months) and overall survival (20.8 vs. 30.4 months) compared to those with lesser degree of elevations. Conclusion Contrary to prior reports, elevation in hemoglobin on VEGF-directed therapy was associated with worse clinical outcomes, and the greater the degree of elevation, the poorer the prognosis.