Journal Article

Pomalidomide for Epistaxis in Hereditary Hemorrhagic Telangiectasia

Pishko, Allyson M., Whitehead, Kevin J., Wisniewski, Lisa, Thomas, Sonia M., Kasthuri, Raj S., Zhou, Jenny Y., Carper, Benjamin A., Marsh, Derek, Clancy, Marianne, McCrae, Keith R., Conrad, Miles B., Parambil, Joseph, Bradley, Lauren, Zumberg, Marc S., Al-Samkari, Hanny, Weiss, Clifford R., Iyer, Vivek N., Decker, Jake E.

2024

Overview

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. 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). 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. 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).

• Publisher: Massachusetts Medical Society
• Subject: Aged / Anemia / Angiogenesis Inhibitors - administration & dosage / Angiogenesis Inhibitors - adverse effects / Bleeding / Coagulation / Constipation / Constipation - chemically induced / Constipation - epidemiology / Double-Blind Method / Drug dosages / Drug Eruptions - epidemiology / Drug Eruptions - etiology / Epistaxis / Epistaxis - diagnosis / Epistaxis - drug therapy / Epistaxis - etiology / Epistaxis - psychology / FDA approval / Female / Genetics / Genetics General / Hematology / Hemoglobin / Hemorrhage / Hereditary hemorrhagic telangiectasia / Humans / Hypothesis testing / Iron / Iron deficiency / Male / Middle Aged / Neutropenia / Neutropenia - chemically induced / Neutropenia - epidemiology / Oncology / Patients / Placebos / Quality of Life / Severity of Illness Index / Statistical analysis / Telangiectasia, Hereditary Hemorrhagic - complications / Telangiectasia, Hereditary Hemorrhagic - drug therapy / Thalidomide - administration & dosage / Thalidomide - adverse effects / Thalidomide - analogs & derivatives / Treatment Outcome