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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| Main Authors: | , , , , , , , , , , |
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| Format: | Article (Journal) |
| Language: | English |
| Published: |
February 2025
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| In: |
Leukemia
Year: 2025, Volume: 39, Issue: 2, Pages: 438-450 |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-024-02479-1 |
| Online Access: | Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41375-024-02479-1 Verlag, kostenfrei, Volltext: http://www.nature.com/articles/s41375-024-02479-1 
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| Author Notes: | 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 |
| Summary: | 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. |
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| Item Description: | Online veröffentlicht: 23. November 2024 Gesehen am 06.05.2025 |
| Physical Description: | Online Resource |
| ISSN: | 1476-5551 |
| DOI: | 10.1038/s41375-024-02479-1 |