Nicolay, Jan P. and Melchers, Susanne and Albrecht, Jana D. and Assaf, Chalid and Dippel, Edgar and Stadler, Rudolf and Wehkamp, Ulrike and Wobser, Marion and Zhao, Jing and Burghaus, Ina and Schneider, Sven and Guelow, Karsten and Goerdt, Sergij and Schuerch, Christian M. and Utikal, Jochen S. and Krammer, Peter H. (2023) Dimethyl fumarate treatment in relapsed and refractory cutaneous T-cell lymphoma: a multicenter phase 2 study. BLOOD, 142 (9). pp. 794-805. ISSN 0006-4971, 1528-0020
Full text not available from this repository. (Request a copy)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 patients with CTCL, creating an urgent need for new and effective therapies. Pathologic constitutive NF-kappa B 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-kappa B and, specifically, kill CTCL cells. To translate these findings to applications in a clinical setting, we performed a multicentric phase 2 study evaluating oral DMF therapy in 25 patients with CTCL stages Ib to IV over 24 weeks (EudraCT number 2014-000924-11/NCT number NCT02546440). End points were safety and efficacy. We evaluated skin involvement (using a modified severity weighted assessment tool [mSWAT]), pruritus, quality of life, and blood involvement, if applicable, as well as translational data. Upon skin analysis, 7 of 23 (30.4%) patients showed a response with >50% reduction in the mSWAT score. Patients with high tumor burden in the 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-kappa B-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 3 study or real-life patient care as well as in combination therapies.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | NF-KAPPA-B; MYCOSIS FUNGOIDES/SEZARY SYNDROME; SEZARY-SYNDROME; INTERNATIONAL-SOCIETY; EUROPEAN-ORGANIZATION; NUCLEAR-FACTOR; TASK-FORCE; ACTIVATION; SURVIVAL; TRANSPLANTATION; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Innere Medizin I |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 09 Apr 2024 12:53 |
| Last Modified: | 09 Apr 2024 12:53 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60778 |
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