Pomalidomide Effective in Hereditary Hemorrhagic Telangiectasia

On Monday, September 23, 2024, a study published in the New England Journal of Medicine highlighted the significant benefits of pomalidomide in reducing the severity of epistaxis for patients with hereditary hemorrhagic telangiectasia (HHT). Conducted by Dr. Hanny Al-Samkari and colleagues from Massachusetts General Hospital in Boston, the trial aimed to evaluate the safety and efficacy of pomalidomide in treating HHT.

The researchers designed a randomized, placebo-controlled trial involving a total of 144 patients. These participants were randomly assigned to two groups: 95 patients received 4 mg of pomalidomide daily for 24 weeks, while the remaining 49 patients were given a placebo. The trial was initiated to determine if pomalidomide could provide a therapeutic benefit in reducing epistaxis, a common and severe symptom of HHT characterized by frequent nosebleeds.

The study proceeded until a planned interim analysis indicated that the efficacy threshold had been met, leading to the trial's early closure in June 2023. At the start of the trial, the average Epistaxis Severity Score among participants was recorded at 5.0 ± 1.5, indicative of moderate-to-severe epistaxis. After the 24-week period, a notable improvement was observed in the pomalidomide group, with a mean reduction in the Epistaxis Severity Score of −0.94 points compared to the placebo group. Additionally, the HHT-specific quality-of-life score showed a mean difference of −1.4 points in favor of the pomalidomide group.

Despite the positive outcomes, the pomalidomide group experienced a higher incidence of adverse events. These included neutropenia, a condition characterized by low levels of neutrophils, a type of white blood cell essential for combating infections. Other side effects reported were constipation and rash. However, the benefits of the drug were most evident during the latter half of the trial and persisted for four weeks following the treatment period. Importantly, the efficacy of pomalidomide was not influenced by the HHT genotype or the initial severity of epistaxis.

The study underscores the potential of pomalidomide as an effective treatment for reducing the severity of epistaxis in HHT patients, offering a significant improvement in their quality of life. The findings are particularly noteworthy as they demonstrate sustained benefits even after the cessation of treatment. This research provides a promising step forward in the management of HHT, a condition that has long posed significant challenges for affected individuals.

Bristol Myers Squibb contributed to the study by donating both the pomalidomide and the matching placebos used in the trial. The results of this study pave the way for further research and potential new treatment protocols that could significantly impact the management of HHT and improve patient outcomes.