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 - Funding Information:
This work was supported in part by the University of Iowa/Mayo Clinic Lymphoma SPORE (CA97274), the Predolin Foundation Biobank (all), and by the Walter B. Frommeyer, Jr., Fellowship Award in Investigative Medicine, University of Alabama at Birmingham (G.G). June Oshiro, PhD, ELS, Mayo Clinic, provided editorial suggestions on an earlier draft of the manuscript.
Funding Information:
This work was supported in part by the University of Iowa/Mayo Clinic Lymphoma SPORE (CA97274), the Predolin Foundation Biobank (all), and by the Walter B. Frommeyer, Jr., Fellowship Award in Investigative Medicine, University of Alabama at Birmingham (G.G). June Oshiro, PhD, ELS, Mayo Clinic, provided editorial suggestions on an earlier draft of the manuscript.
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
VL - 97
SP - 293
EP - 302
JO - American Journal of Hematology
JF - American Journal of Hematology
SN - 0361-8609
IS - 3
ER -