Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia. N Engl J Med 2024 Sep 19;391(11):1015-1027
Date
09/18/2024Pubmed ID
39292928Pubmed Central ID
PMC11412318DOI
10.1056/NEJMoa2312749Scopus ID
2-s2.0-85204418916 (requires institutional sign-in at Scopus site) 26 CitationsAbstract
BACKGROUND: Hereditary hemorrhagic telangiectasia (HHT) is characterized by extensive telangiectasias and arteriovenous malformations. The primary clinical manifestation is epistaxis that results in iron-deficiency anemia and reduced health-related quality of life.
METHODS: We conducted a randomized, placebo-controlled trial to evaluate the safety and efficacy of pomalidomide for the treatment of HHT. We randomly assigned patients, in a 2:1 ratio, to receive pomalidomide at a dose of 4 mg daily or matching placebo for 24 weeks. The primary outcome was the change from baseline through week 24 in the Epistaxis Severity Score (a validated bleeding score in HHT; range, 0 to 10, with higher scores indicating worse bleeding). A reduction of 0.71 points or more is considered clinically significant. A key secondary outcome was the HHT-specific quality-of-life score (range, 0 to 16, with higher scores indicating more limitations).
RESULTS: The trial was closed to enrollment in June 2023 after a planned interim analysis met a prespecified threshold for efficacy. A total of 144 patients underwent randomization; 95 patients were assigned to receive pomalidomide and 49 to receive placebo. The baseline mean (±SD) Epistaxis Severity Score was 5.0±1.5, a finding consistent with moderate-to-severe epistaxis. At 24 weeks, the mean difference between the pomalidomide group and the placebo group in the change from baseline in the Epistaxis Severity Score was -0.94 points (95% confidence interval [CI], -1.57 to -0.31; P = 0.004). The mean difference in the changes in the HHT-specific quality-of-life score between the groups was -1.4 points (95% CI, -2.6 to -0.3). Adverse events that were more common in the pomalidomide group than in the placebo group included neutropenia, constipation, and rash.
CONCLUSIONS: Among patients with HHT, pomalidomide treatment resulted in a significant, clinically relevant reduction in epistaxis severity. No unexpected safety signals were identified. (Funded by the National Heart, Lung, and Blood Institute; PATH-HHT Clinicaltrials.gov number, NCT03910244).
Author List
Al-Samkari H, Kasthuri RS, Iyer VN, Pishko AM, Decker JE, Weiss CR, Whitehead KJ, Conrad MB, Zumberg MS, Zhou JY, Parambil J, Marsh D, Clancy M, Bradley L, Wisniewski L, Carper BA, Thomas SM, McCrae KRAuthor
Jake E. Decker MD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAngiogenesis Inhibitors
Constipation
Double-Blind Method
Drug Eruptions
Epistaxis
Female
Humans
Male
Middle Aged
Neutropenia
Quality of Life
Severity of Illness Index
Telangiectasia, Hereditary Hemorrhagic
Thalidomide
Treatment Outcome
