TY - JOUR
T1 - Sustained, complete response to pexidartinib in a patient with CSF1R-mutated Erdheim–Chester disease
AU - Mayo Clinic-University of Alabama at Birmingham Histiocytosis Working Group
AU - Abeykoon, Jithma P.
AU - Lasho, Terra L.
AU - Dasari, Surendra
AU - Rech, Karen L.
AU - Ranatunga, Wasantha K.
AU - Manske, Michelle K.
AU - Tischer, Alexander
AU - Ravindran, Aishwarya
AU - Young, Jason R.
AU - Tobin, William Oliver
AU - Flanagan, Eoin P.
AU - Nowakowski, Kevin E.
AU - Ruan, Gordon J.
AU - Shah, Mithun V.
AU - Bennani, Nabila Nora
AU - Vassallo, Robert
AU - Ryu, Jay H.
AU - Koster, Matthew J.
AU - Davidge-Pitts, Caroline J.
AU - Patnaik, Mrinal M.
AU - Wu, Xiaosheng
AU - Witzig, Thomas E.
AU - Goyal, Gaurav
AU - Go, Ronald S.
N1 - Publisher Copyright:
© 2022 Wiley Periodicals LLC.
PY - 2022/3/1
Y1 - 2022/3/1
N2 - 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.
AB - 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.
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U2 - 10.1002/ajh.26441
DO - 10.1002/ajh.26441
M3 - Article
C2 - 34978715
AN - SCOPUS:85122266580
SN - 0361-8609
VL - 97
SP - 293
EP - 302
JO - American journal of hematology
JF - American journal of hematology
IS - 3
ER -