Pomalidomide for Hereditary Hemorrhagic Telangiectasia: After Trial Longitudinal Assessment Study (PATH-HHT ATLAS) Open Access

• Pomalidomide was highly effective in treating epistaxis in HHT over extended durations, but less effective for gastrointestinal bleeding.

• Daily doses of 2- or 3-mg pomalidomide daily may achieve an optimal balance of effectiveness and safety/tolerability for bleeding in HHT.

Hereditary hemorrhagic telangiectasia (HHT) causes severe recurrent epistaxis, chronic gastrointestinal bleeding, solid organ arteriovenous malformations, and a profound anemia burden. It is the second most common inherited bleeding disorder worldwide yet remains without approved therapies. The multicenter U.S. randomized, controlled PATH-HHT trial demonstrated efficacy of short-term pomalidomide treatment of epistaxis in HHT. However, many critical questions regarding long-term safety, effectiveness, and utility for HHT-associated gastrointestinal bleeding remain. The PATH-HHT After Trial Longitudinal Assessment Study (NCT07018401) was a multicenter U.S. longitudinal observational study evaluating patients enrolled in PATH-HHT who continued pomalidomide post-PATH-HHT through a post-study drug access program, with ongoing close monitoring per PATH-HHT protocol and as mandated by FDA. Sixty-two patients treated with pomalidomide for HHT for up to 4.4 years were included. Significant, durable improvements in mean Epistaxis Severity Score (5.55 points [baseline] to 2.80 points [month 12], p<0.0001) and mean Hematologic Support Score (9.11 red-cell unit equivalents [RUEs] during 6 months pretreatment to 5.73 RUEs [months 7-12], p=0.0056) were observed. Pomalidomide was less effective for gastrointestinal bleeding than epistaxis, particularly in patients with high RBC transfusion requirements. Thirty-one patients (50%) dose-reduced from 4-mg daily, primarily due to neutropenia, but most maintained effectiveness at 2- or 3-mg daily. Over 105.2 patient-years of pomalidomide treatment, 0 patients developed peripheral neuropathy, 1 developed venous thromboembolism, and 5 developed serious infections. In conclusion, pomalidomide was highly and durably effective for HHT-associated epistaxis, albeit with nontrivial potential toxicities, and may be considered a routine long-term antiangiogenic therapeutic option for certain patients with HHT. NCT07018401