Erdheim–Chester Disease: Investigating the Correlation between Targeted Treatment Therapy and Disease Outcomes

TL;DR

This study explores how targeted therapies affect outcomes in patients with Erdheim–Chester disease, a rare blood-related disorder.

Contribution

The study provides longitudinal insights into treatment responses and monocyte trends in ECD patients receiving targeted versus conventional therapies.

Findings

Partial responses or better were observed in 15 of 20 patients.

Targeted therapy showed trends toward more stable disease but did not reach statistical significance.

No significant differences were found in monocyte levels or outcomes based on treatment type.

Abstract

Erdheim–Chester disease (ECD) is a rare, non-Langerhans cell histiocytic disease, characterized as a clonal hematopoietic malignancy in 2016. MAP kinase and PI3K-AKT pathway somatic mutations and/or fusion genes play significant roles in disease pathogenesis. These mutations now shape the landscape of targetable treatment options for this patient population. Additionally, previous research has shown that patients with ECD have a higher frequency of concomitant myeloid neoplasms as well as mutations traditionally related to clonal hematopoiesis detected in peripheral monocytes. The goals of this study are to examine treatment outcomes with the use of small molecule inhibitors versus conventional therapy in ECD over a longitudinal period. We also aim to identify relevant trends in laboratory parameters, specifically peripheral blood monocytes, that may offer insight into the mechanisms driving disease progression.

A retrospective analysis of 20 adult patients with histopathological and clinical diagnoses of ECD was conducted at a single institution over a twenty-year period (2002–2022). Clinical responses were compared on the basis of treatments rendered, which included chemotherapy, immunotherapy, systemic corticosteroids, surgery and radiation, or targeted agents, referring to any small molecular inhibitors. Treatment response evaluation varied by the anatomic site(s) of disease, the extent of disease at diagnosis, and the imaging modality employed. In this analysis, patients were treated with a combination of targeted agents, myelosuppressive therapies, and radiation at various points in their disease courses. Of these, the most common treatment modality rendered was targeted therapy, employed in 11 of 20 patients. Partial responses or better were observed in 15 of 20 patients. Rates of stable disease trended towards being more frequent with targeted therapy versus conventional therapy but did not reach significance (p = 0.2967). Complete response rates trended towards being more common with conventional therapy than molecular (p = 0.5) but were equivocal overall. Trends of peripheral blood absolute monocytes with relation to disease activity were reviewed as recent literature implied that monocyte levels surrounding disease progression were of potential prognostic significance in histiocytic diseases. Amongst the patients who progressed at any point during their treatment course, absolute monocyte count (in K/µL) was identified at the closest available timepoint prior to or following disease progression and at the lowest value (nadir) following re-institution of therapy prior to any additional agent(s) being employed. There was no statistically significant difference in either of these monocyte values nor in disease outcomes with respect to treatments rendered within our cohort. However, our cohort consists of a heterogenous population of patients with ECD with data that highlights several trends over a longitudinal period, spanning the advent of targeted therapy. Significant differences are anticipated in ongoing analyses.

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