Hanny Al-Samkari, MD, is the Peggy S. Blitz Endowed Chair in hematology and oncology at the Massachusetts General Hospital and an associate professor of medicine at Harvard Medical School.

Hanny Al-Samkari, MD

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

Systemic bevacizumab has proven its safety and efficacy in treating 

 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.

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 

 as a result of small bowel angioectasia bleeding, demonstrated improved hemoglobin levels after several months of bevacizumab treatment.

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.

“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 

. “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.

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.

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; 

 = .0003) and further improved during months 7-12 (0.6 [0-3.5] RBC unit equivalents; 

 >.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 (

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) (

 – .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.

“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.

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.

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

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. 

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Al-Samkari discusses a potentially novel use for bevacizumab in improving outcomes for patients with lesions from non-HHT etiologies.

Patients with HHT Exhibit More Severe Complications Than Previously Believed, With Hanny Al-Samkari, MD

Hereditary hemorrhagic telangiectasia (HHT)

 can result in substantially more frequent and significantly more severe complications than previously thought, according to an analysis of the Comprehensive HHT Outcomes Registry of the United States (CHORUS).

 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.

HHT is the second most common inherited bleeding disorder and is associated with the development of malformed blood vessels. These may be small and cutaneous or mucosal with frequent complications of bleeding, or large and visceral with additional risks that can lead to significant morbidity and mortality. HHT is also notoriously difficult to recognize, particularly in younger patients without a family history of disease or epistaxis.

“For every man with hemophilia, there is ≥1 man and 1 woman with HHT – it’s twice as common as hemophilia, at least,” Al-Samkari told 

 in an exclusive interview. “There are no approved therapies for it. It’s been largely neglected in the hemostasis community – for the longest time, it was really just managed with procedures to treat bleeding, which is not the way to adequately address this disease, as we now know.”

CHORUS is a prospective, multicenter, longitudinal registry enrolling unselected patients with HHT. It contains >2400 data elements, which were collected by trained research coordinators at enrollment and follow-up visits via medical records and direct participant interviews for the purpose of Al-Samkari’s and colleagues’ study.

Investigators included a total of 600 participants with either genetically- or Curacao-criteria-confirmed HHT from November 2023 to April 2025, across 15 HHT centers in the US. Median age was 53 years (range, 0-88), and 60% of patients were female. Most diagnoses were made during mid-to-late adulthood, despite most patients typically displaying manifestations of HHT by age 13.

A total of 568 patients (95%) developed recurrent spontaneous epistaxis, with 339 (60%) developing recurrent epistaxis before age 13. 43% had ≥1 nasal surgery/procedure and 22% had ≥1 medical therapy for epistaxis, such as antifibrinolytic or antiangiogenic. 180 (30%) had a known diagnosis of chronic GI bleeding. Among post-menarche female patients, 124 (34%) had been diagnosed with heavy menstrual bleeding. 247 (41%) reported other clinically significant mucocutaneous oral or skin bleeding.

454 patients (76%) had developed moderate-to-severe HHT-associated mucocutaneous bleeding, which was defined as an Epistaxis Severity Score >4, bleeding requiring targeted pharmaceutical or surgical intervention, intravenous iron, and/or red cell transfusion. This included 334 (56%) with moderate-to-severe HHT-associated epistaxis.

Additionally, 408 patients (68%) had been diagnosed with 

 (n = 351; 59%) or iron deficiency (n = 381; 64%). Of these, 247 (61%) and 150 (37%) required intravenous iron and red blood cell transfusion, respectively. Venous and arterial thromboembolism occurred in 44 (7%) and 38 (6%) patients, respectively, including 34 (6%) with ischemic stroke.

Solid organ AVMs, including brain, pulmonary, and liver, were diagnosed in 81 (15%), 268 (45%), and 128 (21%) patients, respectively. Only 30 with brain AVMs (37%) were diagnosed by age 25. Finally, 16 patients (3%) suffered ≥1 intracranial hemorrhage, with 10 (63%) suffering a first intracranial hemorrhage by age 25. 13 (2%) suffered ≥1 pulmonary hemorrhage.

 in 44 (7%), chronic liver disease in 17 (2.8%), epilepsy in 24 (4%), severe bacterial/deep-seated tissue infection in 35 (6%), and brain abscess in 15 (3%). Serious manifestations occurred in 128 (21%) of patients, and 241 (40%) required emergency room visits and/or hospital admissions for HHT complications.

“These very concerning manifestations, particularly intracranial hemorrhage, can affect people while they’re young,” Al-Samkari said. “Most intracranial hemorrhages in HHT occur before age 25, and the average age of diagnosis was about 37 years. It’s a very concerning diagnostic delay, which we knew was present in HHT, but this study really raised the stakes of just how problematic that delay is.”

Al-Samkari H, Friday C, Kasthuri R, et al. Clinical spectrum of hereditary hemorrhagic telangiectasia (HHT): Data from the comprehensive HHT outcomes registry of the United States (CHORUS). Abstract presented at the 67th American Society of Hematology Annual Meeting. Orlando, FL. December 6-9.

Hammill AM, Wusik K, Kasthuri RS. Hereditary hemorrhagic telangiectasia (HHT): a practical guide to management. Hematology Am Soc Hematol Educ Program. 2021;2021(1):469-477. 

Al-Samkari discusses the slew of HHT-related complications, their frequency, and their severity, highlighting the need for more active intervention.

Ianalumab Improves Stable Response, Reduces Fatigue in ITP, With Hanny Al-Samkari, MD

When combined with eltrombopag, ianalumab prolonged time to treatment failure (TTF), improved stable response at 6 months (SR6), reduced fatigue, facilitated tapering off eltrombopag, and delayed need for subsequent therapy in patients with 

 who had previously received corticosteroids, according to the VAYHIT2 trial.

ITP is an extremely common disorder, typically manifesting as bleeding. Its pathogenesis is highly complicated. ITP is caused by antibodies reacting to glycoproteins expressed on platelets and megakaryocytes, causing shortened survival of circulating platelets and impairing further production. Diminished numbers of regulatory T cells also contribute to its pathogenesis. While corticosteroids are the most common first-line therapy for ITP, they do not lead to durable remissions in most adults with ITP.

 American Society of Hematology (ASH) Annual Meeting and Exposition

 in Orlando, Florida, by Hammy 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 mark the second of 3 phase 3 studies in the VAYHIT program, evaluating the efficacy and safety of ianalumab.

“This is a very potent agent, a BAFF receptor inhibitor, that has a dual mechanism of action – it very potently depletes B cells and prevents the maturation and differentiation of new B cells,” Al-Samkari told 

 in an exclusive interview. “This is of significant potential in a disease driven by autoreactive B cells, particularly when given early in the course of the disease.”

VAYHIT2 was a randomized, double-blind, placebo-controlled phase 3 study. It included patients who had insufficient response to or relapse after first-line corticosteroid therapy (+/0 intravenous immunoglobulin), a platelet count <30x10

/L, and were naïve to and had an indication for second-line ITP treatment. Patients were randomly assigned in a 1:1:1 ratio to eltrombopag plus either ianalumab 9 mg/kg or 3 mg/kg, or placebo. Ianalumab and placebo were delivered as 4 once-monthly intravitreal infusions with eltrombopag for 16 weeks, followed by an 8-week eltrombopag tapering period.

The study’s primary endpoint was TTF, which was defined as time from randomization until platelet count reached <30x10

/L or start of rescue therapy 8 weeks after randomization, start of a new ITP therapy, inability to taper or discontinue eltrombopag by week 24, or death. The key secondary endpoint was SR6, defined as having ≥75% of platelet counts between weeks 19 and 25 being ≥50x10

Ultimately, 152 patients were enrolled in the trial – 50 were assigned to ianalumab 9 mg/kg, 51 to ianalumab 3 mg/kg, and 51 to placebo. The median follow-up period was 12.9 (interquartile range [IQR], 8.6-18), 13.6 (8.4-18.1), and 11.6 (8.1-18.2) months in the 9 mg/kg, 3 mg/kg, and placebo arms, respectively. TTF was substantially longer with ianalumab 9 mg/kg (HR 0.55; 95% CI, 0.32-0.92; log-rank 

 = .021) and ianalumab 3 mg/kg (HR, 0.58; 95% CI, 0.34-0.98; log-rank 

Additionally, substantially more patients achieved SR6 with ianalumab 9 mg/kg (n = 31) versus placebo (n = 20). At the end of the eltrombopag tapering period, fatigue reduction was -7.7 for ianalumab 9 mg/kg and -3.6 for placebo. All grade adverse events were also similar between arms, with grade ≥3 events occurring in 12, 10, and 2 patients in the 9 mg/kg, 3 mg/kg, and placebo arms, respectively. Grade ≥3 neutropenia occurred in 5 and 2 patients in the 9 mg/kg and 3 mg/kg arms, respectively, and no on-treatment events led to ianalumab discontinuations.

Ultimately, Al-Samkari and colleagues determined that ianalumab, when combined with eltrombopag, efficaciously reduces fatigue, facilitates tapering off eltrombopag, prolonged TTF, improved SR6, and delayed the need for subsequent therapy. It was well tolerated with no observed increase in infection risk versus placebo.

“The remaining question, which we will answer with long-term follow-up, is whether ianalumab will be disease-modifying in addition to providing a long duration of treatment-free response,” Al-Samkari said. “Will it allow patients who would have otherwise progressed to a more severe chronic course to have a milder course? That’s something we’re still looking to answer.”

Al-Samkari H, Cuker A, Zaja F, et al. Primary results from VAYHIT2, a randomized, double-blind, phase 3 trial of ianalumab plus eltrombopag versus placebo plus eltrombopag in patients with primary immune thrombocytopenia (ITP) who failed first-line corticosteroid treatment. Abstract presented at the 67

 American Society of Hematology Annual Meeting. Orlando, FL. December 6-9, 2025.

Kistangari G, McCrae KR. Immune thrombocytopenia. Hematol Oncol Clin North Am. 2013;27(3):495-520. 

Al-Samkari discusses the positive results from the VAYHIT2 trial, which investigated ianalumab in combination with eltrombopag in adults with ITP.

Hanny Al-Samkari, MD

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