Real-world outcomes and survival with targeted and established systemic therapies in advanced-stage cutaneous T-cell lymphoma

Brentuximab vedotin (BV), a CD30+ antibody conjugate, was approved for CD30+ cutaneous T-cell lymphoma in 2018. Mogamulizumab, an anti-CCR4 monoclonal antibody was approved for refractory mycosis fungoides and Sézary syndrome. The overall survival (OS) benefit and optimal sequencing of these therapies remain unclear in relation to traditional systemic therapies – bexarotene and extracorporeal photopheresis (ECP) – used in advanced-stage disease. The PROCLIPI study (NCT02848274) was interrogated for patients with advanced-stage disease (2015–2025) receiving mogamulizumab, BV, bexarotene or ECP. Of 593 patients, 566 had recorded systemic therapy. Treatment groups overlapped because most had more than one modality. Extracted data included stage, treatment line, OS and best response [either complete response (CR), partial response (PR), stable disease (SD) or progressive disease (PD)]. Mogamulizumab was given to 72 patients with 52 completed courses. Rates of CR, PR, SD and PD were 31%, 37%, 15% and 17%, respectively, and the median OS was 64 months. BV was given to 83 patients with 69 completed courses. The rates of CR, PR, SD and PD were 12%, 35%, 41%, and 13%, respectively, and the median OS was 28 months. Bexarotene was used in 178 patients (CR, PR, SD and PD in 8%, 37%, 42% and 13%; median OS 48.5 months) and ECP in 153 (CR, PR, SD and PD in 3%, 40%, 46% and 11%; median OS 41 months). In survival analyses (n = 370), OS improved if a patient received mogamulizumab for any line vs. those who received other systemic (P = 0.008). Data for BV did not reach statistical significance. Monoclonal exposure improved OS (P = 0.04). B2 stage favoured mogamulizumab (P = 0.001). Treatment groups were not mutually exclusive. Mogamulizumab demonstrated the highest objective response. Patients receiving mogamulizumab for any line had longer OS, favouring its use in blood-dominant Sézary syndrome. BV produced durable responses, supporting its role in CD30+ large-cell transformation. Shorter OS in BV any line may reflect inadequacies in current staging, as tumour disease (IIB) had worse outcomes than erythrodermic disease (stage III/IV). Bexarotene and ECP remain important systemic therapies. These data inform phenotype-directed sequencing and underscore the need for prospective comparative studies.

Abstract from Crossref