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

Autor: Şener ÖÇ; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Melchers S; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Tengler L; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Beltzig PL; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Albrecht JD; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Tümen D; Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital Regensburg (UKR), Regensburg, Germany., Gülow K; Department of Internal Medicine I, Gastroenterology, Hepatology, Endocrinology, Rheumatology and Infectious diseases, University Hospital Regensburg (UKR), Regensburg, Germany., Utikal JS; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.; DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany., Goerdt S; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany., Hein T; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany.; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany., Nicolay JP; Department of Dermatology, Venereology and Allergology, University Medical Center Mannheim/ University of Heidelberg, Mannheim, Germany. jan.nicolay@umm.de.; Skin Cancer Unit, German Cancer Research Center (DKFZ), Heidelberg, Germany. jan.nicolay@umm.de.; Section of Clinical and Experimental Dermatology, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany. jan.nicolay@umm.de.; DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany. jan.nicolay@umm.de.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2024 Nov 23. Date of Electronic Publication: 2024 Nov 23.
DOI: 10.1038/s41375-024-02479-1
Abstrakt: 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.
Competing Interests: Competing interests: SM received honoraria and travel funding by Kyowa Kirin. KG received consulting fees from Biogen and supports BioMed X as an academic mentor. JSU is on the advisory board or has received honoraria and travel support from Amgen, Bristol Myers Squibb, GSK, Immunocore, LeoPharma, Merck Sharp and Dohme, Novartis, Pierre Fabre, Roche, Sanofi outside the submitted work. JPN received travel and congress participation funding by TEVA and Novartis as well as consulting fees by TEVA, Almirall, Biogen, Novartis, Kyowa Kirin, Innate Pharma, Takeda and Actelion, UCB Pharma and Recordati. ÖÇŞ, LT, PLB, JDA, TH, DT, and SG have no conflict of interest to declare.
(© 2024. The Author(s).)
Databáze: MEDLINE
Externí odkaz: