Lack of Durable Remission with Conventional-Dose Total Skin Electron Therapy for the Management of Sezary Syndrome and Multiply Relapsed Mycosis Fungoides.

Belinda A Campbell,Mathias Bressel,Robert Twigger,Carrie Van Der Weyden,Odette Buelens,Christopher Mccormack,Eleanor Tangas,H Miles Prince,Gail Ryan

doi:10.3390/cancers11111758

Abstract

Mycosis fungoides (MF) and Sezary syndrome (SS) are multi-relapsing, morbid, cutaneous T-cell lymphomas. Optimal treatment sequencing remains undefined. Total skin electron therapy (TSE) is a highly technical, skin-directed treatment, uniquely producing symptom-free and treatment-free intervals. Recent publications favour low-dose TSE for reduced toxicity, but early data support conventional-dose TSE (cdTSE) for longer disease control. Patient selection requires weighing-up tolerability against response durability. We investigated duration of benefit from cdTSE in patients with poorer prognosis diseases: SS and heavily pre-treated MF. Endpoints were overall survival, and “time to next treatment” (TTNT) as surrogate for clinical benefit duration. Seventy patients (53 MF, 17 SS) were eligible: median prior treatments, 4; median cdTSE dose, 30 Gy; median follow-up, 5.8 years. SS patients had worse prognosis (HR = 5.0, p < 0.001) and shorter TTNT (HR = 4.5, p < 0.001) than MF patients; median TTNT was only 3.7 months. Heavily pre-treated MF patients had inferior prognosis (HR = 1.19 per additional line, p = 0.005), and shorter TTNT (HR = 1.13 per additional line, p = 0.031). Median TTNT for MF patients with ≥3 prior treatments was 7.1 months, versus 23.2 months for 0–2 prior treatments. In conclusion, cdTSE has a limited role in SS. TTNT is reduced in heavily pre-treated MF patients, suggesting greater benefit when utilized earlier in treatment sequencing.

Highlights

Mycosis fungoides (MF) and Sezary Syndrome (SS) are diseases with long histories of multiple relapses and significant morbidity
Four of the 5 patients were planned to receive high dose cytotoxic therapy with autologous haematopoietic stem cell transplantation (SCT) followed by conventional-dose TSE (cdTSE), all patients had residual, active skin disease at the time of cdTSE
One patient was planned to receive cdTSE prior to conditioning chemotherapy and allogeneic haematopoietic SCT, this patient had extremely short-lived duration of disease response to cdTSE, with frank progression of skin disease occurring between cdTSE and commencement of chemotherapy and allogeneic SCT

Summary

Introduction

Mycosis fungoides (MF) and Sezary Syndrome (SS) are diseases with long histories of multiple relapses and significant morbidity. The optimal management and sequencing of available treatments remain undefined [1,2,3,4]. Total skin electron therapy (TSE) has been reported to be one of the most effective single agents for MF [7,8] patient selection and endpoint definition undoubtedly play important roles in this assertion. TSE uniquely offers patients a symptom-free and highly desirable treatment-free interlude, the durability of benefit is of critical clinical importance, when weighed against treatment toxicities and increasing availability of systemic treatment options. Prior to the development of skin-active systemic therapies, TSE represented the mainstay of MF treatment, with conventional-dose

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