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@ARTICLE{Nicolay:276211,
author = {J. Nicolay$^*$ and S. Melchers$^*$ and J. D. Albrecht$^*$
and C. Assaf and E. Dippel and R. Stadler and U. Wehkamp and
M. Wobser and J. Zhao and I. Burghaus and S. Schneider and
K. Gülow and S. Goerdt and C. M. Schürch and J. Utikal and
P. Krammer$^*$},
title = {{D}imethyl fumarate treatment in relapsed and refractory
cutaneous {T} cell lymphoma - a multicenter phase {II}
study.},
journal = {Blood},
volume = {142},
number = {9},
issn = {0006-4971},
address = {Washington, DC},
publisher = {American Society of Hematology},
reportid = {DKFZ-2023-01023},
pages = {794-805},
year = {2023},
note = {#EA:A370#LA:D030# / 2023 Aug 31;142(9):794-805},
abstract = {Targeted therapies for cutaneous T-cell lymphoma (CTCL) are
limited and curative approaches are lacking. Furthermore,
relapses and drug induced side effects are major challenges
in the therapeutic management of CTCL patients creating an
urgent need for new, effective therapies. Pathologic
constitutive NF-κB activity leads to apoptosis resistance
in CTCL cells and thus represents a promising therapeutic
target in CTCL. In a preclinical study we showed the
potential of dimethyl fumarate (DMF) to block NF-κB and
specifically kill CTCL cells (Nicolay et al.: Blood 2016).
To translate these findings into a clinical setting, we
performed a multicentric phase II study evaluating oral DMF
therapy in 25 patients with CTCL stage Ib-IV over 24 weeks
(EudraCT number 2014-000924-11/NCT number NCT02546440).
Endpoints were safety and efficacy. We evaluated skin
involvement (mSWAT), pruritus, quality of life and blood
involvement if applicable as well as translational data. In
the skin, 7/23 patients $(30.4\%)$ showed a response with
$>50\%$ reduction in mSWAT. Patients with high tumor burden
in skin and blood responded best to DMF therapy. Although
not generally significant, DMF also improved pruritus in
several patients. Response in the blood was mixed, but we
confirmed the NF-κB inhibiting mechanism of DMF in the
blood. The overall tolerability of the DMF therapy was very
favorable with mostly mild side effects. In conclusion, our
study presents DMF as an effective and excellently tolerable
therapeutic option in CTCL to be further evaluated in a
phase III study or real-life patient care as well as in
combination therapies.},
cin = {A370 / D030},
ddc = {610},
cid = {I:(DE-He78)A370-20160331 / I:(DE-He78)D030-20160331},
pnm = {314 - Immunologie und Krebs (POF4-314)},
pid = {G:(DE-HGF)POF4-314},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37217183},
doi = {10.1182/blood.2022018669},
url = {https://inrepo02.dkfz.de/record/276211},
}