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

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Micro-AbstractVascular endothelial growth factor (VEGF)-targeted agents are extensively used in treatment of renal-cell carcinoma, and treatment-related increases in hemoglobin have been observed in patients with durable responses. In this retrospective study, we found that increases in hemoglobin were associated with significantly shorter time to treatment failure such that higher degrees of hemoglobin elevation portended worse prognosis.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.

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