Advances in the treatment of mycoses fungoides and Sézary syndrome: a narrative update in skin-directed therapies and immune-based treatments

Abstract

Mycoses fungoides (MF) and Sézary syndrome (SS) are cutaneous T-cell lymphomas that are often challenging to manage given the absence of reliably curative therapies, at times high symptom burden with significant detriment to quality of life, and need for ongoing treatment for disease and symptom control. Recent developments in skin-directed treatments include optimizing the use of existing topical therapies, the introduction of known dermatological agents and treatment modalities for the specific treatment of MF/SS (such as mechlorethamine gel, calcineurin inhibitor creams, and photodynamic therapy), and novel local and topical agents. For advanced disease, dedicated clinical trials have translated to exciting progress, leading to the approval of brentuximab vedotin (2017) and mogamulizumab (2018) for relapsed MF/SS. Additional studies of other active systemic agents, including various cellular therapies, represent further attempts to add to the therapeutic armamentarium in treating MF/SS. In this review, we highlight these recent advancements, ranging from optimization of skin-directed therapies to the introduction of novel systemic agents. We focus on therapies approved in the preceding five years or under investigation in advanced-phase clinical trials.

The Role of Cytokines in Cutaneous T Cell Lymphoma: A Focus on the State of the Art and Possible Therapeutic Targets

“…Such evidence in the literature has left the door open to the need for a clear-cut algorithm for patients eligible for biologic therapies. The restoration from a Th2 to a Th1 pattern is also one of the significant goals of the newly available drugs such as Mogamulizumab, Brentuximab Vedotin, and Chlormetine and molecules currently under clinical trial such as Pi3K inhibitors [5,127,[290][291][292][293]. From the present paper reviewing the literature, it has emerged that cytokines can be a reliable marker of some tumorigenic pathway activity, such as JAK/STAT MAPK, and the suppression of those tumorigenic pathways may be monitored by analyzing cytokine composition changes in patients.…”

A Narrative Review of the State of the Art of CCR4-Based Therapies in Cutaneous T-Cell Lymphomas: Focus on Mogamulizumab and Future Treatments

“…Compound [ 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , …”

“…Indeed, the therapeutic armamentarium has been implemented, and an approach has been formed based on the destruction of highly proliferating cells (i.e., the action of chemotherapy). The goal of the newly available drugs is not merely based on the induction of the apoptosis of the neoplastic cells, but it is also found on the reawakening of the host immune system to contrast CTCL [ 5 , 6 , 7 , 9 , 15 , 16 , 17 , 18 ].…”

Clinical and Real-World Effectiveness of Mogamulizumab: A Narrative Review

“…Mycosis fungoides and Sezary syndrome are T-cell lymphomas, and they have been recently reviewed [1][2][3]. The binding of MOG to CCR4-expressing cells has been observed to potentiate antibody-dependent cellular cytotoxicity (ADCC), and subsequently leads to the depletion of the target cells.…”