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@ARTICLE{Giesen:186669,
author = {N. Giesen$^*$ and M. Chatterjee and C. Scheid and A. M.
Poos and B. Besemer and K. Miah$^*$ and A. Benner$^*$ and N.
Becker and T. Moehler and I. Metzler and C. Khandanpour and
A. Seidel-Glaetzer and K. Trautmann-Grill and K. M. Kortüm
and C. Müller-Tidow and G. Mechtersheimer and B. Goeppert
and A. Stenzinger and N. Weinhold and H. Goldschmidt and K.
C. Weisel and M.-S. Raab$^*$},
title = {{A} phase {II} clinical trial of combined {BRAF}/{MEK}
inhibition for {BRAFV}600{E}-mutated multiple myeloma.},
journal = {Blood},
volume = {141},
number = {14},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2023-00038},
pages = {1685-1690},
year = {2023},
note = {#EA:A360#LA:A360# / 2023 Apr 6;141(14):1685-1690},
abstract = {Activating BRAF mutations are found in a small subset of
patients with newly diagnosed multiple myeloma but
prevalence increases in late stage, refractory disease, and
are associated with adverse outcome. This prospective
single-arm, open-label, multicenter phase II trial assessed
the efficacy and safety of combined BRAF/MEK inhibition,
using encorafenib and binimetinib, in patients with
relapsed/refractory multiple myeloma (RRMM) carrying a
BRAFV600E mutation (ClinicalTrials.gov identifier:
NCT02834364). Patients received 450 mg encorafenib once
daily and binimetinib 45 mg twice daily. The primary end
point was the overall response rate achieved within the
first year after start of treatment according to IMWG
criteria. Twelve RRMM patients with a median of 5 prior
lines of therapy were enrolled. The overall response rate
was $83.3\%$ with 10 patients achieving at least a partial
response. The median progression-free survival (PFS) was 5.6
months and overall survival was $55\%$ at 24 months.
Emerging resistance to therapy was driven by RAS mutations
and structural variants involving the BRAF locus. This is
the first prospective clinical trial to demonstrate that
combined BRAF/MEK inhibition is highly effective in patients
with BRAFV600E mutated RRMM and represents a successful
targeted precision medicine approach in this disease.},
cin = {A360 / C060},
ddc = {610},
cid = {I:(DE-He78)A360-20160331 / I:(DE-He78)C060-20160331},
pnm = {311 - Zellbiologie und Tumorbiologie (POF4-311)},
pid = {G:(DE-HGF)POF4-311},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:36608320},
doi = {10.1182/blood.2022017789},
url = {https://inrepo02.dkfz.de/record/186669},
}