Systemic Bevacizumab Improves Chronic Bleeding from GI Lesions, With Hanny Al-Samkari, MD

Systemic bevacizumab has proven its safety and efficacy in treating severe chronic bleeding from gastrointestinal (GI) vascular lesions across a variety of non-hereditary hemorrhagic telangiectasia (HHT) etiologies – including idiopathic angiodysplasia, esophageal varices, and von Willebrand disease – among adult and elderly patients, according to data from a recent observational study.1

Previous case studies have investigated systemic bevacizumab for various forms of GI bleeding. A patient with HHT and a massive transfusion dependence saw drastic improvement in required red blood cell (RBC) transfusions after 12 months of treatment with bevacizumab. Another patient, a 69-year-old man with severe anemia as a result of small bowel angioectasia bleeding, demonstrated improved hemoglobin levels after several months of bevacizumab treatment.2,3

Presented at the 67th American Society of Hematology (ASH) Annual Meeting and Exposition in Orlando, Florida, by Hanny Al-Samkari, MD, the Peggy S. Blitz Endowed Chair in hematology and oncology at the Massachusetts General Hospital and associate professor of medicine at Harvard Medical School, these data may provide a more efficient and longer-lasting method of treating severe chronic bleeding compared to surgical interventions.1

“Right now, the standard of care is to go in and do local ablation with argon plasma, coagulation, clipping, and things like this to the lesions,” Al-Samkari told HCPLive. “But all these conditions have an underlying angiogenic dysregulation such that there’s excessive angiogenic signal. And the more tissue injury you do, the more lesions you provoke to grow. You go in, you cauterize, you do whatever you can, but then a few months later, the bleeding is back, and often worse than before.”

Al-Samkari and colleagues conducted an observational study of patients with non-HHT severe chronic bleeding from GI vascular lesions of any etiology refractory to standard therapies, who had been treated with off-label systemic bevacizumab. The primary endpoint was hematologic support requirements, such as RBC transfusions and intravenous (IV) iron infusions, measured in RBC unit equivalents (1 RBC unit equivalent = 1 RBC unit or 250 mg IV elemental iron). Secondary endpoints included hemoglobin, IV iron, and RBC transfusions measured independently, as well as safety.1

A total of 23 patients with chronic, severe bleeding received bevacizumab. The median age was 78 years (range, 42-90), and all but 1 patient was ≥60 years. All patients began treatment at 5 mg/kg daily (77%) or 2.5 mm/kg daily (23%) and were infused every 2 weeks for 4 treatments, followed by 2.5-5 mg/kg daily every 4 weeks. Treatment lasted for up to 4.2 years.1

Ultimately, hematologic support required substantially improved from 6 months pretreatment (median 14.2 RBC unit equivalents [interquartile range [IQR] 10-23.9]) during months 1-6 (4.1 [2-7.1] RBC unit equivalents; P = .0003) and further improved during months 7-12 (0.6 [0-3.5] RBC unit equivalents; P >.001). These improvements coincided with improvements in median (IQR) hemoglobin, measured at 8.2 (7.7-9.4) g/dL at baseline, 10.1 (8.6-12.9) g/dL at month 3, 12.2 (9.6-13) g/dL at month 6, 10.6 (8.8-13.1) g/dL at month 9, and 10.4 (8.9-13.3) g/dL at month 12 of bevacizumab treatment (P = .0039).1

Additionally, patients in the cohort required 60 emergency department visits or hospital admissions specifically for GI vascular lesion bleeding in the 12 months prior to initiation, compared to 21 in the 12 months after the initiation. The median number of visits and admissions per patient improved from 3.5 (IQR, 1-5) to 1 (0-1.25) (P – .0049). Proteinuria was the most common treatment-emergent adverse event (TEAE), occurring in 7 patients (30%), followed by hypertension in 6 (26%) and fatigue in 3 (13%). No venous or arterial thromboembolic events occurred, and no fatal TEAEs were noted. Ultimately, 3 patients discontinued for TEAEs, all of which were grade 3 proteinuria, and 5 discontinued for inadequate treatment effect.1

“Not only did bevacizumab trigger a dramatic improvement in Hematologic Support Score, it reduced hospitalizations and emergency department visits, specifically due to vascular GI bleeding in these patients, by >50% in the year after versus the year before starting bevacizumab,” Al-Samkari said. “And it did it pretty safely; most patients were able to deal with the side effects and stay out of the hospital with monthly to every 2-month low-dose bevacizumab infusions.”

Editor’s Note: Al-Samkari reports disclosures with Pharmacosmos, Agios, Amgen, Vaderis, Novartis, Sobi, and others.

References

1. Ayad N, Al-Samkari H. Long-term safety and effectiveness of systemic bevacizumab for chronic severe bleeding in idiopathic gastrointestinal angiodysplasia, esophageal varices, and angiodysplasia of von Willebrand disease and acquired von Willebrand syndrome. Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

2. Ou G, Galorport C, Enns R. Bevacizumab and gastrointestinal bleeding in hereditary hemorrhagic telangiectasia. World J Gastrointest Surg. 2016;8(12):792-795. doi:10.4240/wjgs.v8.i12.792

3. Compare D, Sgamato C, Rocco A, et al. Long-term bevacizumab is safe and effective in managing small bowel angioectasias bleeding refractory to conventional treatments: a case report. Gastroenterol Rep (Oxf). 2024;12:goae070. Published 2024 Jul 6. doi:10.1093/gastro/goae070