Abstract 4536: Investigating the correlation between molecular diagnostics, targeted therapies and treatment outcomes in Rosai Dorfman disease: a single-institution experience
Authors: Reynolds Samuel B. , Wilcox Sabrina R. , Talpaz Moshe , Ahmed Asra Z. 
Published: April 2023

Introduction: Rosai Dorfman Disease (RDD) is a non-Langerhans cell histiocytic disease whose pathologic features include sinus histiocytosis with variable emperipolesis. Traditional management consists of local therapies (resection, radiation) for limited lesions and myelosuppressive therapies for systemic disease. Recent studies, however, have identified MAP Kinase pathway mutations in RDD, prompting further research into the utility of targeted agents.

Methods: A retrospective analysis was conducted at a single institution over a 20-year period (2002-2022) of 40 patients with RDD. Inclusion criteria included age ≥18 and histopathologic evidence of RDD without obscuring secondary malignancies. Clinical data points included biological gender, age at diagnosis, molecular diagnostics, imaging and therapies administered. Binary data was utilized for statistical analysis and comparison of outcomes by treatment type, time to diagnosis and use of targeted agents.

Results: In this analysis, 72% of patients were female and 28% male with an average age at diagnosis of 45.8 years, over 50% of whom were diagnosed between 1 and 12 months of presentation. Primary disease was most commonly extranodal (&gt;90%), found in cutaneous, osseous and CNS structures (50%, 36% and 16.6%, respectively). Regarding management, surgery was most common in &gt;36% of patients, followed by steroid and myelosuppressive therapies (25% each), immunotherapy (13.88%) and targeted molecular therapies (11.1%). Disease responses were considered stable if grossly unchanged during serial exam or imaging surveillance, partial if diminished but still present and complete if disease was grossly and radiographically resolved; a partial response or better was observed in &gt;75% of patients. With respect to treatment rendered, stable disease was equally likely between recipients of molecular and conventional (non-molecular) therapy at 25%. Partial responses were higher in molecular therapy recipients (75% as compared to 42%), although complete responses have not yet been observed in this cohort. Patients diagnosed at &lt;1 month from symptom onset had higher rates of disease stability and complete responses compared to those diagnosed at &gt;24 months.

Conclusions: To our knowledge, this study is the largest of its kind in adult Rosai Dorfman Disease. Early recognition and utilization of targeted molecular therapies, based on our preliminary data, are associated with higher rates of achieving disease stability and at least a partial response. The current absence of complete responses in patients receiving targeted molecular therapy is likely attributable to the still-emerging use of these agents and interim response assessments not yet being completed. Higher complete response rates in targeted agents relative to conventional therapies are anticipated in ongoing analyses.

Citation Format: Samuel B. Reynolds, Sabrina R. Wilcox, Moshe Talpaz, Asra Z. Ahmed. Investigating the correlation between molecular diagnostics, targeted therapies and treatment outcomes in Rosai Dorfman disease: a single-institution experience. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4536.