Characteristics Associated with Clinical Response to Pomalidomide in Hereditary Hemorrhagic Telangiectasia

Abstract

Hereditary hemorrhagic telangiectasia (HHT) results in recurrent severe epistaxis, chronic gastrointestinal bleeding, and other morbid manifestations. Pomalidomide was recently demonstrated to be efficacious for bleeding in HHT in the landmark PATH-HHT trial. Given that the vascular remodeling that results in bleeding improvement may require several months, characteristics associated with treatment response would be invaluable to plan treatment. Using data from PATH-HHT (NCT03910244), we identified characteristics associated with change from baseline in Epistaxis Severity Score (ESS, a well-validated 10-point HHT bleeding scale and the trial's primary endpoint) using multivariable-adjusted repeated measures models. Characteristics associated with a better response to pomalidomide at weeks 16-24 of the trial included a higher (more severe) baseline ESS (change from baseline, -0.76 [95% CI -0.99,-0.54] points per 1 point higher baseline score, P<0.001) and concomitant antifibrinolytic therapy (-0.73 [95% CI -1.48, 0.01] vs. no therapy, p=0.05). Characteristics associated with a less robust response were older age (0.29 [95% CI 0.05, 0.53] per 10 years older, P=0.02) and underlying ACVRL1 germline mutation (0.62 [95% CI -0.04,1.27] vs. ENG, SMAD4 or mutation not known, p=0.06]. Characteristics notably associated with placebo response (placebo effect) were patient-reported outcome measures, such that those experiencing more severe disease at baseline had less placebo effect. In conclusion, several baseline patient and disease characteristics were associated with pomalidomide response, findings that may help guide patient selection for the use of pomalidomide in HHT. Clinicaltrials.gov identifier: NCT03910244.