Evaluating Two New Options for Hereditary Hemorrhagic Telangiectasia

At EHA2021 Virtual, researchers shared safety and efficacy findings of two agents for the treatment of the rare disease hereditary hemorrhagic telangiectasia (HHT): pazopanib and bevacizumab. Hanny Al-Samkari, MD, of Massachusetts General Hospital, presented findings from both studies.

“HHT is a rare, progressive multisystem bleeding disorder of abnormal vessel formation causing chronic gastrointestinal hemorrhage, epistaxis, and severe iron-deficiency anemia,” Dr. Al-Samkari explained, and there is no FDA-approved therapeutic for its treatment.

In the first study, researchers evaluated pazopanib, an oral multi-kinase angiogenesis inhibitor intended to treat severe HHT-associated bleeding. The study enrolled 13 patients with red blood cell (RBC)–transfusion-dependent HHT and severe epistaxis and/or gastrointestinal bleeding. Transfusion dependence was defined as requiring ≥2 packed RBC units per month for ≥3 months.

Patients’ median age was 66 years. Twelve patients (92%) were on medical disability due to severe chronic bleeding and anemia and five (38%) had been recommended to pursue palliative care as all available therapeutic options had been exhausted, the authors noted. Notably, eight patients (62%) had previously received systemic bevacizumab but had no response.

Participants received pazopanib at a median dose of 100 mg/day (range = 25-300 mg/day) for a median of 22 months. All participants achieved RBC transfusion independence. Compared with baseline, after 12 months of treatment, pazopanib increased mean hemoglobin by 4.8 g/dL (7.8 vs. 12.7 g/dL; p<0.0001) and decreased mean epistaxis severity score by 4.77 points (7.20 vs. 2.43 points; p<0.0001). Most patients (n=11) experienced freedom from anemia at 12 months.

Compared with the three months before pazopanib treatment, RBC transfusions decreased by 93% (from 16.0 to 0.0 units; p<0.0001). These improvements were maintained over time, the researchers noted. The number of required hemostatic procedures also decreased by 90% (from a median of 4 to 0; p=0.0002).

The authors also reported that pazopanib was well-tolerated, and the most common adverse events (AEs) were hypertension (31%), lymphocytopenia (23%), and fatigue (23%). Together with the efficacy findings, the tolerable safety profile suggests that pazopanib is a promising option for managing HHT-related severe bleeding, “durably liberating all patients from transfusion dependence and normalizing hematologic parameters at doses much lower than the dose used to treat malignancies.”

In the second study, Dr. Al-Samkari shared results from a study of bevacizumab, an anti-vascular endothelial growth factor antibody, to treat bleeding and resultant anemia in HHT by suppressing telangiectasia formation. The researchers conducted a retrospective study of 238 patients who were treated with bevacizumab for a median of 12 months.

Mean patient age was 63 years (range = 29-91). Primary bleeding source was epistaxis in 42% and gastrointestinal bleeding in 19%, and 39% had primary bleeding in both sources.

Comparing outcomes in the pretreatment period and the bevacizumab treatment period, the researchers found that bevacizumab increased mean hemoglobin by 3.2 g/dL (8.6 g/dL vs. 11.8 g/dL; p<0.0001). Treatment also decreased the epistaxis severity score by 3.4 points (6.8 vs. 3.4; p<0.0001). The median number of RBC units transfused decreased by 82% (9.0 vs. 0; p<0.0001) compared with the six months prior to study treatment.

Bevacizumab was effective regardless of disease severity, Dr. Al-Samkari noted, with similar outcomes in patients with different underlying pathogenic mutations. The researchers also reported that a schedule of continuous bevacizumab maintenance achieved higher hemoglobin and lower epistaxis severity scores than intermittent or as-needed maintenance (in response to recurrence of bleeding symptoms or iron deficiency).

Regarding safety, 38% of patients experienced AEs attributable to bevacizumab. The most common of these were hypertension (18%), fatigue (10%), proteinuria (9%), and myalgia/arthralgia (6%). A total of 5% of patients discontinued treatment due to AEs.

“Systemic bevacizumab was highly effective to manage chronic bleeding and iron deficiency anemia in HHT, with dramatic improvements in hemoglobin, red cell transfusion and iron infusion requirements, and epistaxis severity,” the researchers concluded.

The findings of these reports are limited by the small study populations, and the retrospective nature of the bevacizumab study.

The authors report relationships with Novartis and Amgen, the study drug’s manufacturers.


  1. Parambil J, Gossage J, McCrae K, et al. Pazopanib for severe bleeding and transfusion-dependent anemia in hereditary hemorrhagic telangiectasia. Abstract S103. Presented at the EHA 2021 Virtual Congress, June 9-17, 2021.
  2. Al-Samkari H, Kasthuri R, Albitar H, et al. An international multicenter study of systemic bevacizumab for bleeding in hereditary hemorrhagic telangiectasia: the InHIBIT-BLEED study. Abstract S320. Presented at the EHA 2021 Virtual Congress, June 9-17, 2021.