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Dimethyl fumarate and extracorporeal photopheresis combination-therapy synergize in inducing specific cell death and long-term remission in cutaneous T cell lymphoma: lymphoma

Primary cutaneous T cell lymphomas (CTCL) are characterized by high relapse rates to initially highly effective therapies. Combination therapies have proven beneficial, particularly if they incorporate extracorporeal photopheresis (ECP). The NF-κB inhibitor dimethyl fumarate (DMF) has proven a new,...

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Hauptverfasser: Şener Gürsoy, Özge Çiçek (VerfasserIn) , Melchers, Susanne (VerfasserIn) , Tengler, Luisa (VerfasserIn) , Beltzig, Paul L. (VerfasserIn) , Albrecht, Jana Dorothea (VerfasserIn) , Tümen, Deniz (VerfasserIn) , Gülow, Karsten (VerfasserIn) , Utikal, Jochen (VerfasserIn) , Goerdt, Sergij (VerfasserIn) , Hein, Tobias (VerfasserIn) , Nicolay, Jan Peter (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: February 2025
In: Leukemia
Year: 2025, Jahrgang: 39, Heft: 2, Pages: 438-450
ISSN:1476-5551
DOI:10.1038/s41375-024-02479-1
Online-Zugang:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-024-02479-1
Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41375-024-02479-1
Volltext
Verfasserangaben:Özge Ç Şener, Susanne Melchers, Luisa Tengler, Paul L. Beltzig, Jana D. Albrecht, Deniz Tümen, Karsten Gülow, Jochen S. Utikal, Sergij Goerdt, Tobias Hein and Jan P. Nicolay
Beschreibung
Zusammenfassung:Primary cutaneous T cell lymphomas (CTCL) are characterized by high relapse rates to initially highly effective therapies. Combination therapies have proven beneficial, particularly if they incorporate extracorporeal photopheresis (ECP). The NF-κB inhibitor dimethyl fumarate (DMF) has proven a new, effective drug in CTCL in a clinical phase II study. In vitro experiments with patient-derived SS cells and the CTCL cell lines HH, HuT 78, and SeAx revealed a synergistic effect of DMF and ECP on cell death induction in CTCL cells. Furthermore, an additional increase in the capacity to inhibit NF-κB in CTCL was detected for the combination treatment compared to DMF monotherapy. The same synergistic effects could be measured for ROS production via decreased Thioredoxin reductase activity and glutathione levels. Consequently, a cell death inhibitor screen indicated that the DMF/ECP combination treatment induces a variety of cell death mechanisms in CTCL. As a first step into clinical translation, 4 patients were already treated with the DMF/ECP combination therapy with an overall response rate of 100% and a time to next treatment in skin and blood of up to 57 months. Therefore, our study introduces the combination treatment of DMF and ECP as a highly effective and long-lasting CTCL therapy.
Beschreibung:Online veröffentlicht: 23. November 2024
Gesehen am 06.05.2025
Beschreibung:Online Resource
ISSN:1476-5551
DOI:10.1038/s41375-024-02479-1

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