Clinical trial successfully treats rare blood disorder

Clinical trials have demonstrated that the anti-cancer drug pomalidomide is safe and effective for treating hereditary hemorrhagic telangiectasia (HHT), a rare bleeding disorder that affects more than 1 in 5,000 people worldwide.

The trial, led by Dr. Keith McRae of the Cleveland Clinic, was stopped early due to these successful findings. New England Journal of Medicine.

The impetus for this study was a patient: About 15 years ago, Dr. McCrae, chief of benign hematology at the Cleveland Clinic and senior author of the study, saw a patient with symptoms of HHT. At the time, there was very little information available about the disease, says Dr. McCrae, a hematologist and scientist.

HHT is Blood vessels The hair becomes abnormally tangled and twisted. This can lead to excessive nosebleeds, a hallmark of the disease. HHT can also cause bleeding in the digestive tract, which can lead to serious complications in the lungs, liver, and brain. Bleeding worsens with age, affecting quality of life and can lead to anemia and other life-threatening conditions. There are no FDA-approved medications for the long-term management of HHT.

The patient, then in his 50s, suffered from nosebleeds and severe gastrointestinal bleeding. He required several blood transfusions and multiple injections of concentrated plasma clotting factors every week. He was told that his only option was surgery to remove the diseased intestine, which would have a significant impact on his quality of life.

Dr. McRae began looking for new options and the cancer medicine Thalidomide is Positive results In several patients with similar symptoms, Dr. McCray treated them with low doses of the drug, and within two to three weeks the bleeding almost completely stopped. Dr. McCray has also tried thalidomide on other patients with similar HHT symptoms, who also responded well.

“It was amazing,” Dr. MacRae said. “I'd never seen anything like it before. Clinical Experienceand I thought it was important to study this.”

Thalidomide is a drug used primarily to treat multiple myeloma. Serious Side EffectsSo instead of pursuing a large-scale study with thalidomide, Dr. McRae used a drug with a similar chemical structure called pomalidomide, which is FDA-approved to treat bone marrow cancer. He Pilot Study When used in combination with pomalidomide, the drug was found to be effective and safe.

To study pomalidomide, researchers enrolled 144 adults with HHT at 11 medical centers in the United States between November 2019 and June 2023. Patient advocacy group CureHHT actively supported enrollment in the clinical trial.

All participants had moderate to severe nosebleeds and required iron supplementation or blood transfusions. RTI International in North Carolina served as the data coordinating center for the study, and C5Research, an academic research organization (ARO) at the Cleveland Clinic, served as the clinical coordinating center.

The researchers observed that HHT patients who took pomalidomide experienced a significant reduction in the severity of nosebleeds, required fewer blood transfusions and iron infusions, and had an improved quality of life. In June 2023, an interim analysis found pomalidomide to be effective, and the trial was closed.

The researchers speculate that pomalidomide works by blocking the growth of abnormal blood vessels. “The drug may normalize blood vessel structure or thicken blood vessel walls, potentially reducing their fragility,” said Dr. McCrae, but more research is needed.

“It's extremely rare to find a treatment that works for a rare disease, so this is a real success story,” said Andrei Kinzerski, M.D., program chief in the Division of Blood Disorders and Resources at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health. “To date, no effective therapies have been tested to treat HHT.”

Kinzerski said the discovery has broader life-saving implications for people with more severe HHT, who can also develop malformed blood vessels in organs such as the lungs, liver and brain, which can lead to hemorrhagic strokes, pulmonary hemorrhage and heart failure.

Although the researchers did not follow up with participants after the trial ended, Dr. McRae said some patients in the trial experienced no recurrence of nosebleeds for up to six months after stopping the drug, suggesting the drug may show promise as a long-term or intermittent treatment, he said.

Even if an effective treatment for this rare disease is found, much remains unknown about the mechanism of HHT itself. Dr. McCrae hopes to secure additional funding to continue his research into HHT and uncover the mechanisms behind the disease and the effects of pomalidomide and other drugs on them.

“We are optimistic that learning more about how this treatment works will have a major impact on the treatment of HHT hematology and our understanding of vascular malformations,” he says.