Session: 102. Regulation of Iron Metabolism: Translating Iron Biology to the Clinic
Hematology Disease Topics & Pathways:
Adult, antibodies, Biological, Bleeding Disorders, Anemias, Diseases, Therapies, Hemostasis, Bleeding and clotting, Elderly, Biological Processes, iron deficiency, Young Adult, Study Population, Clinically relevant, Vascular Wall, iron metabolism
Methods: All HHT patients treated with systemic bevacizumab for chronic bleeding were selected for retrospective analysis. Data was collected for each patient over a 14-month course, divided into a pretreatment period (six months), induction period (two months), and maintenance period (six months) and included demographics, baseline HHT characteristics, epistaxis grade, surgical interventions, bevacizumab dosing, adverse events, hemoglobin, red cell transfusions, intravenous iron infusions, and other anemia and/or bleeding-directed therapies. Additionally, the peak hemoglobin on bevacizumab over the course of all available follow-up was collected for each patient. Our institution’s bevacizumab treatment pathway began with an induction phase (5 mg/kg of IV bevacizumab every two weeks for four treatments) followed by a maintenance phase (5 mg/kg administered monthly thereafter). Statistical tests used in data analysis included the paired t-test, Wilcoxon signed rank test, and Fisher’s exact test.
Results: 13 HHT patients were treated with bevacizumab for chronic bleeding for a median of 13.9 (range, 4.9-30.1) months. Baseline patient characteristics are shown in Table 1 and hematologic parameters during the pretreatment, induction, and maintenance periods are shown in Table 2. Compared with pretreatment values, bevacizumab treatment increased the mean hemoglobin by 4.0 g/dL (95% CI, 2.6-5.3 g/dL) [mean (95% CI) hemoglobin 8.5 (7.8, 9.9) g/dL versus 12.5 (11.2, 13.7) g/dL, p<0.001)], reduced red cell units transfused by 92% [median of 6 (range, 0-59) units versus 0 (range, 0-15) units, p=0.004], and reduced quantity of iron infused by 73% [mean (95% CI) 462 (257, 668) mg/month versus 126 (75, 178) mg/month, p=0.002]. The peak hemoglobin value measured over the course of all available follow up ranged from 12.1-17.6 mg/dL (Figure 1), with all but two patients (85%) achieving a hemoglobin within the normal range for gender. Twelve of 13 patients did not require red cell transfusions during the entire maintenance period and 11 of 13 patients did not require iron infusions during the latter half of the maintenance period (Figure 2). Epistaxis control (reduction of epistaxis grade to <2) was achieved in 85% with bevacizumab, versus 0% before treatment (p<0.001) and all but one patient experienced improvement in epistaxis grade. No patient required nasal or GI procedures during the maintenance period. Four out of 5 patients receiving antifibrinolytic agents or erythropoiesis-stimulating agents prior to initiation of bevacizumab were able to discontinue these agents during bevacizumab induction and not resume them thereafter. Bevacizumab was well-tolerated, with two patients (15%) developing grade 3 hypertension requiring medical management.
Conclusions: Systemic bevacizumab was highly effective to treat chronic bleeding and iron deficiency anemia in HHT. This study is the first to demonstrate the impact of bevacizumab on objective hematologic parameters, such as hemoglobin and iron infusion requirements. Further study is needed to confirm the benefit magnitude and define optimal dosing, treatment duration, and long-term safety.
Disclosures: Al-Samkari: Agios: Consultancy. Kuter: Protalex: Research Funding; Rigel: Consultancy, Research Funding; Novartis: Consultancy; Amgen Inc.: Consultancy; Argenx: Consultancy; Bioverativ: Consultancy, Research Funding; BMS: Research Funding; Syntimmune: Consultancy; Pfizer: Consultancy; Dova Pharmaceuticals: Consultancy, Membership on an entity's Board of Directors or advisory committees; Principia: Research Funding; ONO: Consultancy.
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