Tre-O2-01 - Assessing the efficacy of mogamulizumab: a novel tool for the management of mycosis fungoides and Sézary syndrome

Abstract

<h3>Introduction:</h3> A novel monoclonal antibody therapy termed mogamulizumab is currently seeking approval for treatment of mycosis fungoides and Sézary syndrome. Mogamulizumab is a humanized IgG1 κ monoclonal antibody which targets C-C chemokine receptor type 4 (CCR4), a transmembrane chemokine receptor which promotes T cell migration to the skin and is expressed at high levels on the surface of the malignant cells which drive cutaneous lymphomas. <h3>Methods:</h3> We performed a multi-centre clinical audit using data from 16 patients who have received mogamulizumab through a patient access programme at The Christie (8) and University Hospitals Birmingham (8) NHS Foundation Trusts. Our cohort had a median age of 68.1 (57.1–71.5) years at initiation of treatment, with a male to female sex ratio of 1.67 and varied diagnoses including Sézary syndrome (62.5%), classical mycosis fungoides (18.8%) and folliculotropic mycosis fungoides (12.5%). We assessed objective measures of disease response in the skin (mSWAT scores) and blood (flow cytometry), progression free survival (PFS) and the incidence of adverse events with the aim to further assess the efficacy and safety of mogamulizumab in this setting. <h3>Results:</h3> The patients in our cohort showed significant responses to mogamulizumab with median mSWAT score falling from 108 (53.8–139.1) to 23.1 (8.8–75.0) at peak response which was achieved at a median of 202 (115.5–328) days. 31.3% of our patients achieved a complete skin response whilst 37.5% achieved a partial skin response. The flow cytometry results of our cohort showed a marked improvement after initiation of mogamulizumab with median CD4/CD8 ratio, median number of circulating CD4+CD7– and CD4+CD26–being reduced by 89.0%, 96.8% and 95.8% respectively with median time to peak response being 193 (139.75–305.25) days. 62.5% of patients achieved a complete blood response with a further 25% achieving a partial blood response. Mogamulizumab was generally well tolerated with a median number of CTCAE events of 1.5 (0–4.25), which were predominantly grade 1 (62.9%) followed by grade 2 (22.9%) and grade 3 (14.3%) with no higher-grade adverse events being reported by any of the patients who had received mogamulizumab. One patient did discontinue treatment due to toxicity. Progression was only seen in 2 of the 16 with a medium follow up of 267 days (194.3–462.8) The median PFS has not been reached. 3 of the 16 patients have died, causes of death were CTCL (1), squamous cell carcinoma (1) and upper gastrointestinal haemorrhage (1). <h3>Conclusion:</h3> Mogamulizumab treatment resulted in marked improvements in skin and blood disease activity for patients across both centres whilst being generally well tolerated. The median PFS has not been reached after a median FU of 8.9 months. This compares favourably with the PFS of 7.7 months seen in the MAVORIC study. This observational study confirmed a high response rate in blood and skin in this group of diseases.