Kim YH, et al. - In previously treated cutaneous T-cell lymphoma patients, the comparison between mogamulizumab (a novel monoclonal antibody directed against C-C chemokine receptor 4) and vorinostat was performed with a focus on the efficacy of both of these agents. They observed a significantly prolonged progression-free survival in patients treated with mogamulizumab vs vorinostat. Moreover, findings demonstrated the efficacy of mogamulizumab as a novel treatment option for patients with mycosis fungoides and, importantly, for Sézary syndrome, a subtype that represents a major therapeutic challenge in cutaneous T-cell lymphoma.

Methods

• This is an open-label, international, phase 3, randomised controlled trial.
• For this study, researchers recruited patients with relapsed or refractory mycosis fungoides or Sézary syndrome at 61 medical centres in the USA, Denmark, France, Italy, Germany, the Netherlands, Spain, Switzerland, the UK, Japan, and Australia.
• Patients aged at least 18 years (in Japan, ≥20 years), had failed (for progression or toxicity as assessed by the principal investigator) at least one previous systemic therapy, and had an Eastern Cooperative Oncology Group performance score of 1 or less and adequate haematological, hepatic, and renal function were considered eligible.
• Using an interactive voice web response system, random assignment of patients (1:1) to mogamulizumab (1·0 mg/kg intravenously on a weekly basis for the first 28-day cycle, then on days 1 and 15 of subsequent cycles) or vorinostat (400 mg daily) was carried out.
• On the basis of cutaneous T-cell lymphoma subtype (mycosis fungoides vs Sézary syndrome) and disease stage (IB–II vs III–IV), stratification was carried out.
• Patients and investigators were not masked to treatment assignment as this study was open label.
• Progression-free survival by investigator assessment in the intention-to-treat population was the primary endpoint.
• They also performed safety analyses including patients who received one or more doses of study drug.

Results

• The intention-to-treat population involved eligible patients who were randomly assigned to receive mogamulizumab (n=186) or vorinostat (n=186) between Dec 12, 2012, and Jan 29, 2016.
• The safety population comprised 370 patients as two patients randomly assigned to mogamulizumab withdrew consent before receiving study treatment.
• Mogamulizumab therapy vs vorinostat therapy provided superior investigator-assessed progression-free survival (median 7·7 months [95% CI 5·7–10·3] in the mogamulizumab group vs 3·1 months [2·9–4·1] in the vorinostat group; hazard ratio 0·53, 95% CI 0·41–0·69; stratified log-rank p<0·0001).
• A total of 75 (41%) of 184 patients in the mogamulizumab group and 76 (41%) of 186 patients in the vorinostat group suffered the grade 3–4 adverse events of any cause.
• Pyrexia observed in eight (4%) patients and cellulitis in five (3%) patients represented the most common serious adverse events of any cause in the mogamulizumab group; while the most common serious adverse events of any cause in the vorinostat group was cellulitis in six (3%) patients, pulmonary embolism in six (3%) patients, and sepsis in five (3%) patients.
• Findings revealed that 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.