LY06 Golidocitinib-based therapy in relapsed or refractory mycosis fungoides and Sézary syndrome: a real-world retrospective analysis

Abstract

Cutaneous T-cell lymphoma (CTCL), primarily mycosis fungoides (MF) and Sézary syndrome (SS), is an incurable malignancy characterized by skin-tropic malignant CD4+ T cells. Current therapies for relapsed or refractory disease exhibit limited efficacy, and patients with transformed disease face dismal outcomes. Somatic Janus kinase (JAK)1 and JAK3 mutations often drive constitutive JAK–signal transducer and activator of transcription activation in CTCL, promoting oncogenesis and resistance. Golidocitinib, a potent and selective JAK1 inhibitor, has previously demonstrated antitumour activity in relapsed or refractory peripheral T-cell lymphoma. This study aims to evaluate the real-world clinical benefit, efficacy and safety of golidocitinib-based therapy – administered either as monotherapy or in combination regimens – for the treatment of patients with relapsed or refractory MF or SS. A real-world retrospective analysis was conducted with a data cutoff of 22 July 2025. Ten patients received at least one cycle of golidocitinib. The cohort had a median age of 57.4 years and a median of 2 prior systemic therapies. The majority of patients (n = 9, 90%) received combination therapy, all incorporating brentuximab vedotin (BV), while one patient received monotherapy. Most patients presented with advanced disease features, including large cell transformation and high CLIPI scores. The best overall response rate and skin response rate were both 80% (8 of 10), comprising 8 partial responses. One patient maintained stable disease, and one experienced progression. Notably, four patients who had previously relapsed or not responded to BV therapy responded to the ­golidocitinib–BV combination. The median time to response was 31.5 days. Regarding safety, treatment-related adverse events (TRAEs) occurred in six patients, primarily cytomegalovirus infection (50%) and thrombocytopenia (30%). This pioneering real-world study demonstrates that golidocitinib-based regimens offer favourable clinical efficacy in patients with relapsed or refractory MF or SS, including those refractory to prior BV. Subsequent prospective trials are warranted to further validate these combination strategies.