Health-Related Quality of Life Among Individuals With Histiocytic Neoplasms in the Modern Era of Targeted Therapies

Background: Histiocytic neoplasms include Langerhans cell histiocytosis (LCH), Erdheim-Chester disease (ECD), and Rosai-Dorfman disease (RDD). The discovery of MAPK pathway mutations has led to the approval of BRAF and MEK inhibitors, reducing disease-specific mortality. There is a critical need to define the health-related quality of life (HRQoL) among adults with histiocytic neoplasms in the modern era of targeted therapies. Methods: We conducted a multi-institutional study including 196 adults with histiocytic neoplasms (73 LCH, 67 ECD, and 56 RDD) who completed the Patient-Reported Outcomes Measurement Information System (PROMIS)-29 + 2 Profile v2.1, including 48 with longitudinal assessments. A total of 113 (57.7%) patients were not receiving treatment at the time of baseline survey. Primary endpoints were physical health (PH) and mental health (MH) summary scores, and the secondary outcome was the PROMIS Preference (PROPr) score, an overall health utility metric. Results: Patients with ECD had worse PH scores than those with LCH or RDD (odds ratio [OR], 4.82; P =.006). Single-system pulmonary LCH (OR, 5.99; P =.028) and multisystem disease (OR, 2.49; P =.018) were also associated with worse PH scores than single-system disease. Multisystem disease was associated with worse MH scores (OR, 2.17; P =.036). An exploratory mixed-model longitudinal analysis (n=48) demonstrated improvements in PH scores among patients with ECD and in MH and PROPr scores among those with LCH over a median follow-up of 6 months. Conclusions: Within histiocytic neoplasms, ECD and multisystem involvement define a high-risk HRQoL phenotype characterized by multidomain impairment. Longitudinal data suggest potential improvements in select domains with targeted therapy. However, mean scores remained below population norms. These patients may benefit from proactive, bundled supportive care and closer HRQoL monitoring.