Sustained, complete response to pexidartinib in a patient with CSF1R-mutated Erdheim-Chester disease.

ABSTRACT: Erdheim-Chester disease (ECD) is a histiocytic neoplasm that predominantly harbors mitogen-activated protein kinase (MAPK) pathway variants. MAPK inhibitors typically are effective treatments, but mutations outside the MAPK pathway, such as CSF1R variants, may cause refractory ECD. We describe a patient with a novel somatic mutation in CSF1R (CSF1R^{R549_E554delinsQ} ) that resulted in refractory ECD affecting the central nervous system. Cell model studies, RNA sequencing analysis, and in silico protein modeling suggested that she had a gain-of-function mutation occurring in a region critical for autoinhibition. The patient was treated with pexidartinib, a CSF1R inhibitor, and has had a complete clinical and metabolic response lasting more than 1.5 years to date. To our knowledge,

SUBMITTER: Abeykoon JP 

PROVIDER: S-EPMC9536810 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature