Sotatercept in Pulmonary Langerhans Cell Histiocytosis‐Associated Pulmonary Hypertension: A Case Series and Systematic Review

Abstract

Pulmonary Langerhans cell histiocytosis (PLCH) frequently complicated by pulmonary hypertension (PH), which markedly worsens prognosis. We retrospectively reviewed three institutional PLCH-PH cases treated with off-label Sotatercept added to background triple therapy and performed a systematic review of published PLCH-PH reports (PubMed/Embase through May 2025). Our three patients (ages 69, 62, 49; all female) had progressive vascular disease despite optimized vasodilator therapy. Following Sotatercept, all experienced ≥ 3-fold increases in 6-min walk distance and improved functional class. Hemodynamics improved substantially: right-atrial pressure -78.6%, pulmonary vascular resistance -75.5%, pulmonary artery systolic pressure -58.5%, mean PAP - 56.0%, PA diastolic pressure -51.0%, PAWP - 47.1%; cardiac output and index rose +75.9% and +73.8%, respectively. BNP/NT-proBNP normalized. Systematic review identified 34 published cases (2010-2025): mean age 37.2 ± 13.7 years, 44.1% female, 45.7% current/former smokers. Reported management strategies included targeted vasodilators, cytotoxic PLCH therapies (e.g., cladribine), smoking cessation, and selective surgery/transplant. In this small series, Sotatercept added to background therapy produced marked clinical and hemodynamic gains in refractory PLCH-PH. These effects of Sotatercept in Group 5 PH-are encouraging but limited by sample size and retrospective design. Prospective, collaborative studies are needed to define safety, efficacy, and optimal patient selection.