Introduction & Objectives

Targeted therapies for cutaneous T-cell lymphoma (CTCL) are limited and curative approaches are still lacking. Relapses and drug induced side effects are main challenges in the therapeutic management of CTCL patients resulting in an urgent need for new, effective therapies. Constitutive NFκB activity leads to apoptosis resistance in CTCL cells which contributes to the pathogenesis and therapy resistance of these cells. We showed in a preclinical study, that both in isolated CTCL patient cells and in a CTCL xenograft mouse model, NFκB inhibition with the small-molecule drug dimethyl fumarate (DMF) effectively and specifically induces CTCL cell death and thus bears promising therapeutic potential in CTCL (Nicolay JP et al.: Blood 2016). In order to prove these effects in a clinical setting and to extend the therapeutic spectrum in CTCL, we performed the present study.

Materials & Methods

We performed a multicentric phase II study in 6 CTCL centers in Germany to investigate DMF therapy in CTCL patients. 25 patients with CTCL stage Ib-IV were included and orally treated with DMF for 24 weeks. Primary endpoints were safety and efficacy. We evaluated skin involvement (mSWAT), pruritus, quality of life as well as blood involvement if applicable.

Results

Between 2016 and 2020 25 patients with CTCL stage Ib-IV were screened for the study, 22 patients were evaluable per protocol. In the skin, 7/22 patients (31.8%) showed a response with >50% reduction of the mSWAT. The waterfall plot for the best response is shown in Fig.1. The overall median mSWAT for all patients decreased by 22 % from Screening to End of treatment. The overall tolerability of the DMF therapy was very favorable with only rather mild side effects. The evaluation of the secondary end points will be presented at the EORTC meeting.

Conclusions

Our results indicate that DMF leads to a significant reduction of the mSWAT in around a third of stage Ib-IV CTCL patients with a very favorable side effect profile. Thus, our study presents DMF as a promising and well-tolerable therapeutic option in CTCL to be further evaluated in a phase III study or real-life patient care.

Figure 1: Waterfall plot for best response in skin (y-axis shows % reduction in mSWAT)