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

Academic Article


  • 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 (CSF1RR549_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, this is the first report to describe successful treatment of a patient with ECD by using an agent that specifically targets CSF1R. This case also highlights the critical role of individualized molecular profiling to identify novel therapeutic targets in ECD.
  • Published In

    Digital Object Identifier (doi)

    Author List

  • Abeykoon JP; Lasho TL; Dasari S; Rech KL; Ranatunga WK; Manske MK; Tischer A; Ravindran A; Young JR; Tobin WO
  • Start Page

  • 293
  • End Page

  • 302
  • Volume

  • 97
  • Issue

  • 3