Overall survival after intravenous iron use in patients with cancer and iron deficiency: A propensity-matched real-world study.

11128 Background: Iron deficiency affects up to two-thirds of patients with cancer and frequently coexists with anemia, with the highest prevalence in pancreatic, colorectal, and lung cancers. Functional iron deficiency driven by cancer-related inflammation predominates. Although intravenous (IV) iron is recommended to improve hematologic outcomes and reduce transfusion requirements, its impact on survival remains uncertain. We evaluated the association between IV iron use and overall survival (OS) in patients with advanced solid tumors using large real-world data. Methods: We conducted a retrospective cohort study using a TriNetX, a federated electronic health record network. Adults with solid malignancies and laboratory-defined iron deficiency (TSAT ≤ 20% and ferritin ≤ 500 ng/mL) were identified and categorized by IV iron exposure. Cohorts were matched 1:1 using propensity score matching for demographics, comorbidities, cancer site, iron indices (ferritin, transferrin saturation), hemoglobin, and treatment-related variables. OS was assessed using Kaplan–Meier analysis (5-year cap) and Cox proportional hazards modeling. Results: After propensity matching, 4,802 patients receiving IV iron were compared with 4,751 patients who did not receive IV iron, with a good balance across baseline characteristics. In Kaplan–Meier analysis (capped at 5 years), median overall survival (OS) was 875 days in the IV iron group and 858 days in the no IV iron group, with similar 5-year survival probabilities (38.6% vs 37.5%) and no significant difference by log-rank testing (p=0.53). On multivariable Cox proportional hazards modeling, IV iron exposure was not independently associated with mortality (HR 1.04, 95% CI 0.996–1.094; p=0.075). Male sex (HR 1.09, p<0.0001) and increasing age (HR 1.013 per year, p<0.0001) were associated with higher mortality. Iron indices demonstrated strong prognostic associations, with low transferrin saturation (<10%: HR 1.48; 10–20%: HR 1.24; both p<0.0001) and anemia diagnoses including iron deficiency anemia (HR 1.05, p=0.0048) and anemia of chronic disease (HR 1.23, p<0.0001) independently associated with increased mortality, while lower ferritin levels were associated with improved survival (<100 ng/mL: HR 0.53; 100–200 ng/mL: HR 0.78; both p<0.0001). Cancer site was also independently associated with OS, with higher mortality observed in digestive, respiratory, urinary tract, and central nervous system malignancies, and improved survival in breast and thyroid/endocrine cancers. Conclusions: In this large propensity-matched real-world cohort, IV iron was not associated with worse overall survival in patients with cancer and iron deficiency, supporting its survival safety while highlighting iron indices, anemia, and cancer type as key prognostic markers.