Abstract 4537: Erdheim Chester disease: A retrospective study characterizing the molecular and pathologic footprints with clinical presentation and comparative outcomes in the present era of targeted molecular targeted therapy

Erdheim Chester Disease (ECD) is a rare, non-Langerhans cell histiocytic disease, characterized as a neoplastic disorder in 2016. MAP Kinase and PI3-AKT pathway somatic mutations and/or fusion genes have been shown to play a significant role in disease pathogenesis. Despite this, molecular sequencing at diagnosis has yet to become a standard of practice. Retrospective analysis of 19 patients diagnosed with ECD at a single institution over a twenty-years (2002-2022) was conducted. Inclusion criteria were patients 18 years or older, histopathologic diagnosis of ECD, and clinical correlation of disease. The following was collected for each patient: biological sex, age at diagnosis, molecular testing (if utilized), immunohistochemistry, imaging results, therapies administered and best treatment outcomes. Information was translated into binary data for statistical analysis. In this analysis, 47% of patients were females; average age at diagnosis was 51.2 years. 36% of patients were diagnosed within 12 months of symptoms onset. Molecular diagnostics were utilized in 100% of patients, (immunohistochemistry 94%, sequencing 26%). Primary disease was most commonly extranodal (94%), followed by osseous (63%), dermal (52%) and the central nervous system (36%). Treatment consisted of targeted molecular therapy most often (57%), followed by myelosuppressive therapy and steroids (42%), and immunotherapy or radiation (10% each). Disease responses were considered stable if grossly unchanged clinical exam or imaging surveillance, partial (PR) if diminished but still present and complete (CR) if disease was grossly or radiographically resolved. A PR or better was observed in 83% of patients. Stable disease was seen more often in patients treated with conventional therapy (33%) as compared to targeted molecular therapy (11%). PR was higher in targeted therapy recipients (55%). CR was more common with conventional therapy than molecular (66% vs 33%). Patients diagnosed within 1 month of symptom onset had higher rates of disease stability, compared to diagnosis at > 24 months (50% compared to 25%). To our knowledge, this is one of the largest studies of its kind conducted in adult ECD. Targeted molecular therapy utilization by this analysis is associated with higher rates of partial disease response as compared to conventional therapy. The opposite was observed in complete responders. Use of targeted molecular therapies is very recent and higher CR rates are expected in ongoing analyses and longer patient follow-up. Moreover, molecular diagnostics were not routinely employed at diagnosis which delayed the initiation of treatment. Thus, we strongly advocate for early genetic profiling at the time of ECD diagnosis and utilization of targeted therapies when actionable mutations are observed. Citation Format: Sabrina R. Wilcox, Samuel B. Reynolds, Jennifer Girard, Asra Ahmed. Erdheim Chester disease: A retrospective study characterizing the molecular and pathologic footprints with clinical presentation and comparative outcomes in the present era of targeted molecular targeted therapy. [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 4537.