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

Autor: Abeykoon JP; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Lasho TL; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Dasari S; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Rech KL; Division of Hematopathology, Mayo Clinic, Rochester, Minnesota, USA., Ranatunga WK; Department of Health Sciences Research, Mayo Clinic, Rochester, Minnesota, USA., Manske MK; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Tischer A; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Ravindran A; Division of Hematopathology, Mayo Clinic, Rochester, Minnesota, USA., Young JR; Department of Radiology, Mayo Clinic, Jacksonville, Florida, USA., Tobin WO; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA., Flanagan EP; Department of Neurology, Mayo Clinic, Rochester, Minnesota, USA., Nowakowski KE; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Ruan GJ; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Shah MV; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Bennani NN; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Vassallo R; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA., Ryu JH; Division of Pulmonary and Critical Care Medicine, Mayo Clinic, Rochester, Minnesota, USA., Koster MJ; Division of Rheumatology, Mayo Clinic, Rochester, Minnesota, USA., Davidge-Pitts CJ; Division of Endocrinology, Diabetes, Metabolism and Nutrition, Mayo Clinic, Rochester, Minnesota, USA., Patnaik MM; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Wu X; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Witzig TE; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Goyal G; Division of Hematology-Oncology, University of Alabama at Birmingham, Birmingham, Alabama, USA.; Research Collaborator (Limited-Tenure), Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA., Go RS; Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Jazyk: angličtina
Zdroj: American journal of hematology [Am J Hematol] 2022 Mar 01; Vol. 97 (3), pp. 293-302. Date of Electronic Publication: 2022 Jan 03.
DOI: 10.1002/ajh.26441
Abstrakt: 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, 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.
(© 2022 Wiley Periodicals LLC.)
Databáze: MEDLINE
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