Cutaneous T-Cell Lymphoma
A group of lymphomas where malignant T cells primarily affect the skin. Romidepsin, a cyclic depsipeptide that inhibits histone deacetylase (HDAC), is approved for cutaneous T-cell lymphoma that has progressed after prior treatment.
Technical Context
CTCL subtypes: mycosis fungoides (MF — patches, plaques, tumours on skin; indolent course) and Sézary syndrome (SS — erythroderma + circulating malignant T cells; aggressive). Romidepsin (Istodax): cyclic depsipeptide (bicyclic, containing a disulphide bond that is reduced intracellularly to activate the compound) that inhibits class I HDACs (histone deacetylases). HDAC inhibition → histone hyperacetylation → chromatin remodelling → reactivation of silenced tumour suppressor genes + direct pro-apoptotic effects. FDA approval: relapsed/refractory CTCL (GPI-04-0001 trial: ORR approximately 34%, complete response approximately 6%) and relapsed/refractory PTCL. Romidepsin is administered as IV infusion over 4 hours on days 1, 8, 15 of a 28-day cycle. Key toxicities: nausea, fatigue, thrombocytopenia, and ECG changes (QT prolongation monitoring required).