Allogeneic haematopoietic stem cell transplantation for advanced stage mycosis fungoides and Sézary syndrome: never-late, never-never?

Abstract

Mycosis fungoides (MF) and Sézary syndrome (SS) constitute the majority of primary cutaneous T-cell lymphomas accounting up to 80% of cases with a median age at diagnosis of 55–60 years. Inherently variable in their clinical behaviour, MF/SS are generally considered incurable. Early-stage disease involves skin patches and plaques (stage I–IIA) and generally has an indolent clinical course with excellent long-term survival rates. Conversely, advancedstage disease (stage IIB–IV) which involves tumours, erythroderma or significant blood, nodal or visceral involvement, carries a poor prognosis with a median survival ranging from 2 to 5 years [1, 2]. For patients with advanced-stage disease and in patients with refractory early-stage disease, there are a multitude of therapeutic challenges. Clinicians are constantly faced with lack of effective therapies which have low response rates, short remissions of typically less than 6 months, requiring multiple successive lines of therapy [3]. More recently, targeted therapies such as the antibody drug conjugate brentuximab vedotin for patients with CD30 positive disease and the antibody to CCR4 mogamulizumab have emerged as promising agents [4, 5]. However, unlike in many other lymphomas, despite these advances, no conventional therapy is curative for advanced-stage MF/SS. Indeed, for those patients of suitable age (unfortunately only ~50% of patients eligible given the average age of presentation) and performance status and with an identifiable donor, allogeneic hematopoietic stem cell transplantation (alloSCT) remains the only potential curative option and has been clearly demonstrated to achieve a cure in selected patients. To date, the body of evidence is limited to retrospective single centre studies, registry data and small prospective studies with no randomised controlled trials. In this issue of Bone Marrow Transplantation, Domingo-Domenech et al. present an important update of the outcomes of European Society for Blood and Marrow Transplantation (EBMT) alloSCT registry for advancedstage MF/SS. This analysis included 113 patients and is an extended series of the previously reported outcomes of 60 cases published in 2010, along with an extended follow-up reported in 2014 [6, 7]. Primary endpoints revealed a 5-year predicted median progression free survival (PFS) of 26% (95% CI 19–36%) and an overall survival (OS) of 38% (95% CI 30–49%), respectively. This study represents one of two large patient cohorts with the longest follow-up of surviving patients and complements the large study from the Centre for International Bone Marrow Transplantation Research (CIBMTR) published in 2014, both demonstrating a durable response with alloSCT; the CIBMTR study included 129 patients with MF/SS revealing a 5-year predicted PFS of 17% (95% CI 9–26%) and an OS of 32% (95% CI 22–44%) [8]. Moreover, a recent meta-analysis by Iqbal et al., which included a total of 266 patients from five studies, revealed an attractive pooled OS of 59% (95% CI 50–69%) but a PFS of only 36% (95% CI 27–45%), highlighting the increased risk of disease relapse post alloSCT [9]. Indeed, in this meta-analysis 47% (95% CI 41–53%) relapsed/progressed following alloSCT which was comparable to the 5year relapse/progression in the EBMT study of 45% (95% CI 35–54%). The apparent plateau in the survival curve beyond two years as observed in this analysis provides further support that alloSCT can achieve a cure for some patients with * H. Miles Prince [email protected]