Hepcidin Levels and Erythropoietin Alfa Resistance In Patients with Chemotherapy Induced Anemia (CIA)

Abstract Abstract 3216 Introduction: Hepcidin is a key regulator of iron metabolism and is a central mediator of anemia associated with inflammation. Hepcidin has previously been associated with resistance to ESAs in renal anemia and may also be a potential mediator of ESA resistance in chemotherapy-induced anemia (CIA). We therefore assessed hepcidin in a cohort of patients with CIA who received erythropoietin alfa (EPREX, Janssen-Cilag, Ltd.) as part of a post-approval safety study. Patients and Methods: All subjects were anemic (defined as baseline Hb ≤11 g/dL) and almost all patients had one of the following malignancies: breast, ovarian, gastric and pancreatic cancer, myeloma. Patients were receiving standard doses of EPREX for management of CIA. Patients with anemia secondary to iron deficiency (defined as transferrin saturation ≤ 20%) were excluded from study enrollment. Serum erythropoietin was not assessed as a condition of eligibility. Hemoglobin (Hb) response was defined as an increase of ≥ 1 g/dL through week 4. Baseline serum hepcidin levels were measured retrospectively using a hepcidin C-ELISA. The relationships between hepcidin, Hb, iron status (serum iron, ferritin, transferrin saturation), C-Reactive Protein (CRP) (a marker of inflammation and surrogate for IL-6 activity) and Hb response were evaluated. Results: Among 51 anemic patients with a median age of 56 (range 25–72), 42 were Hb responders. None of the patients studied received blood transfusions during the first 4 weeks of treatment. No significant difference in baseline hepcidin or CRP levels was found between the Hb responders and non-responders; hepcidin 129.43 ng/mL (9.5-722.4) versus 210.7 (9.9-399.6) and CRP 47.1 nmol/L (0-428.6) versus 46.0 (2.1-1145.7) respectively. All subjects who had a decrease in Hb through week 4 were tumor non-responders. Baseline hepcidin levels were inversely correlated with baseline Hb (p = 0.04) but did not predict for Hb response. Neither did baseline CRP nor iron status. Adjusting hepcidin for iron status did not improve predictive accuracy. No significant correlation was found between CRP change at week 4 and Hb response. A correlation was found between baseline hepcidin and week 4 CRP (p = 0.0004) but not with baseline CRP levels. Conclusions: Baseline hepcidin was not predictive of Hb response to ESA therapy. Hepcidin change may be a better predictor and warrants further evaluation. Lack of information on baseline erythropoietin levels is a significant limitation of this study. Correlation with additional markers (e.g., soluble transferrin receptor, inflammatory markers like IL-6) will also be important to fully determine the role of hepcidin as a predictor for EPO resistance in settings of chronic inflammation. Disclosures: Rijnbeek: Johnson & Johnson: Employment. Reddy:Johnson & Johnson: Employment. Li:Johnson & Johnson: Employment. Vercammen:Johnson & Johnson: Employment. Cornfeld:Johnson & Johnson: Employment.