A Six-year Response to Belinostat in a Highly Probable Case of Relapsed/Refractory MF/SS Initially Classified as...

Cutaneous T-cell lymphomas (CTCLs) are a heterogeneous group of hematological malignancies, whose diagnosis is often delayed and requires highly individualized therapeutic strategies. We report an unusual case of a highly probable r/r MF/SS in a 66-year-old male initially diagnosed with peripheral T-cell lymphoma, not otherwise specified (PTCL-NOS), based on an atypical leukemic presentation without skin involvement. Cutaneous lesions developed during the disease course, prompting then for a retrospective diagnostic reassessment. Expression of KIR3DL2 on circulating malignant cells, along with a clonal TCR-gamma rearrangement present in both the blood and the skin, and a TP53 nonsense variant, led to a revision of the diagnosis to mycosis fungoides (MF) and Sézary syndrome (SS). MF/SS are the most prevalent CTCL subtypes and are associated with a poor prognosis in advanced stages, largely due to the lack of effective treatments that can achieve sustained remission. Therapeutic options for patients with relapsed/refractory (r/r) MF/SS remain limited and long-term disease control is uncommon. After failure of two treatment lines, including CHOEP-based chemotherapy and bendamustine-brentuximab vedotin (B-BV), the patient received belinostat, a histone deacetylase inhibitor (HDACi). Following three cycles of belinostat, complete cutaneous remission and a partial hematological response were achieved and have been maintained for more than six years (79 cycles to date). Treatment was well tolerated, with only mild anemia. This case highlights the potential role of belinostat in the management of advanced MF/SS and suggests that durable disease control may be achievable in selected r/r patients. Further investigations are warranted to better identify the patients most likely to benefit from belinostat therapy.