Background: Cutaneous T-cell lymphomas are rare non-Hodgkin lymphomas with substantial morbidity and mortality in advanced disease stages. We compared the effectiveness of mogamulizumab, a singular monoclonal antibody directed against C-C chemokine receptor 4, with vorinostat in patients with formerly treated cutaneous T-cell lymphoma.

Methods: Within this open-label, worldwide, phase 3, randomised controlled trial, we employed patients with relapsed or refractory mycosis fungoides or S¡§|zary syndrome at 61 medical centres in the united states, Denmark, France, Italia, Germany, holland, The country, Europe, the United kingdom, Japan, and Australia. Qualified patients were aged a minimum of 18 years (in Japan, ?Y20 years), had unsuccessful (for progression or toxicity as assessed through the principal investigator) a minumum of one previous systemic therapy, coupled with an Eastern Cooperative Oncology Group performance score of just one or fewer and sufficient haematological, hepatic, and kidney function. Patients were at random assigned (1:1) utilizing an interactive voice web response system to mogamulizumab (1?¡è0 mg/kg intravenously every week for that first 28-day cycle, after that time days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily). Stratification was by cutaneous T-cell lymphoma subtype (mycosis fungoides versus S¡§|zary syndrome) and disease stage (IB-II versus III-IV). Because this study was open label, patients and investigators weren’t masked to treatment assignment. The main endpoint was progression-free survival by investigator assessment within the intention-to-treat population. Patients who received a number of doses of study drug were incorporated within the safety analyses. This research is ongoing, and enrolment is finished. This trial was registered with ClinicalTrials.gov, number NCT01728805.

Findings: Between 12 , 12, 2012, and Jan 29, 2016, 372 qualified patients were at random allotted to receive mogamulizumab (n=186) or vorinostat (n=186), including the intention-to-treat population. Two patients at random allotted to mogamulizumab withdrew consent before receiving study treatment thus, 370 patients were incorporated within the safety population. Mogamulizumab therapy led to superior investigator-assessed progression-free survival in contrast to vorinostat therapy (median 7?¡è7 several weeks [95% CI 5?¡è7-10?¡è3] within the mogamulizumab group versus 3?¡è1 several weeks [2?¡è9-4?¡è1] within the vorinostat group hazard ratio 0?¡è53, 95% CI 0?¡è41-0?¡è69 stratified log-rank p<0?¡è0001). Grade 3-4 adverse events of any cause were reported in 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group. The most common serious adverse events of any cause were pyrexia in eight (4%) patients and cellulitis in five (3%) patients in the mogamulizumab group and cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients in the vorinostat group. Two (67%) of three on-treatment deaths with mogamulizumab (due to sepsis and polymyositis) and three (33%) of nine on-treatment deaths with vorinostat (two due to pulmonary embolism and one due to bronchopneumonia) were considered treatment-related.

Interpretation: Mogamulizumab significantly prolonged progression-free survival compared with vorinostat, and could provide a new, effective treatment for patients with mycosis fungoides and, importantly, for S¡§|zary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma.