• Hanny Al-Samkari, Raj S Kasthuri, Vivek N Iyer, Allyson M Pishko, Jake E Decker, Clifford R Weiss, Kevin J Whitehead, Miles B Conrad, Marc S Zumberg, Jenny Y Zhou, Joseph Parambil, Derek Marsh, Marianne Clancy, Lauren Bradley, Lisa Wisniewski, Benjamin A Carper, Sonia M Thomas, and Keith R McCrae.
• From Massachusetts General Hospital, Boston (H.A.-S.); University of North Carolina, Chapel Hill (R.S.K.), and RTI International, Research Triangle Park (D.M., L.B., B.A.C., S.M.T.) - both in North Carolina; Mayo Clinic, Rochester, MN (V.N.I.); University of Pennsylvania, Philadelphia (A.M.P.); Medical College of Wisconsin, Milwaukee (J.E.D.); Johns Hopkins University, Baltimore (C.R.W.), and CureHHT, Monkton (M.C.) - both in Maryland; University of Utah, Salt Lake City (K.J.W.); University of California, San Francisco, San Francisco (M.B.C.); University of Florida, Gainesville (M.S.Z.); University of California, San Diego, La Jolla (J.Y.Z.); and Taussig Cancer Center and Lerner Research Institute (K.R.M.), Cleveland Clinic (J.P., L.W., K.R.M.), Cleveland.
• N. Engl. J. Med. 2024 Sep 19; 391 (11): 101510271015-1027.

BackgroundHereditary 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.MethodsWe 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).ResultsThe 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.ConclusionsAmong 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).Copyright © 2024 Massachusetts Medical Society.

34 keywords...

hide…