Pomalidomide Significantly Reduces Epistaxis Severity in HHT Patients, Study Finds
Researchers have found that the severity of epistaxis significantly diminishes in affected patients with hereditary hemorrhagic telangiectasia (HHT) with pomalidomide treatment. HHT is a genetic disorder characterized by the growth of widespread telangiectasias and arteriovenous malformations which causes recurrent nosebleeds or epistaxis, iron-deficiency anemia, and diminished quality of life. Epistaxis can be severe and debilitating, highly affecting patients' daily activities and overall well-being. A recent study was conducted by Al-Samkari and colleagues and was published in The New England Journal of Medicine.
The primary objective of this study was to investigate whether pomalidomide lessens the severity of epistaxis in HHT patients, as defined by the Epistaxis Severity Score. An important secondary outcome was how pomalidomide impacts patient quality of life: to be measured with a specific HHT quality-of-life score.
144 Patients were randomized to receive either pomalidomide (4 mg daily) or placebo for 24 weeks in a 2:1 ratio. The first objective was the change from baseline to week 24 in the Epistaxis Severity Score. This score is standardized from 0 to 10, with higher values indicating a more significant bleeding, and any decrease with a value of at least 0.71 points is considered clinically relevant. The secondary endpoint was the HHT-specific quality-of-life score, ranging from 0 to 16, with higher values meaning more restrictions.
Results
• At baseline for all patients the mean Epistaxis Severity Score was 5.0 ± 1.5, denoting moderate to severe nosebleeds.
• At week 24, the mean change in Epistaxis Severity Score was -0.94 points for the pomalidomide group compared with the placebo group (95% CI, −1.57 to −0.31; P=0.004), crossing the clinically significant threshold of 0.71 points.
• Compared with the placebo group, the mean difference in HHT-specific quality of life between baseline and end was −1.4 points (95% CI, −2.6 to −0.3), suggesting improvement in daily functioning and reduction of disease-related limitations.
• Neutropenia, constipation, and rash were more common in the pomalidomide group, but no new safety signals emerged.
Pomalidomide markedly decreased the severity of epistaxis, a HHT, on the criterion of clinical significance for more than half of those affected. The treatment also seemed to improve quality of life, and safety. Therefore, pomalidomide could be a promising therapeutic intervention in HHT, but more studies are needed to adequately describe its long-term benefits and safety across the larger populations of affected individuals.
Reference:
Al-Samkari, H., Kasthuri, R. S., Iyer, V. N., Pishko, A. M., Decker, J. E., Weiss, C. R., Whitehead, K. J., Conrad, M. B., Zumberg, M. S., Zhou, J. Y., Parambil, J., Marsh, D., Clancy, M., Bradley, L., Wisniewski, L., Carper, B. A., Thomas, S. M., & McCrae, K. R. (2024). Pomalidomide for epistaxis in hereditary hemorrhagic telangiectasia. The New England Journal of Medicine, 391(11), 1015–1027. https://doi.org/10.1056/nejmoa2312749
