Global patterns of care in advanced stage mycosis fungoides/Sezary syndrome: a multicenter retrospective follow-up study from the Cutaneous Lymphoma International Consortium

ABSTRACT Background Advanced-stage mycosis fungoides (MF)/Sezary syndrome (SS) patients are weighted by an unfavorable prognosis and share an unmet clinical need of effective treatments. International guidelines are available detailing treatment options for the different stages but without recommending treatments in any particular order due to lack of comparative trials. The aims of this second CLIC study were to retrospectively analyze the pattern of care worldwide for advanced-stage MF/SS patients, the distribution of treatments according to geographical areas (USA versus non-USA), and whether the heterogeneity of approaches has potential impact on survival. Patients and methods This study included 853 patients from 21 specialist centers (14 European, 4 USA, 1 each Australian, Brazilian, and Japanese). Results Heterogeneity of treatment approaches was found, with up to 24 different modalities or combinations used as first-line and 36% of patients receiving four or more treatments. Stage IIB disease was most frequently treated by total-skin-electron-beam radiotherapy, bexarotene and gemcitabine; erythrodermic and SS patients by extracorporeal photochemotherapy, and stage IVA2 by polychemotherapy. Significant differences were found between USA and non-USA centers, with bexarotene, photopheresis and histone deacetylase inhibitors most frequently prescribed for first-line treatment in USA while phototherapy, interferon, chlorambucil and gemcitabine in non-USA centers. These differences did not significantly impact on survival. However, when considering death and therapy change as competing risk events and the impact of first treatment line on both events, both monochemotherapy (SHR = 2.07) and polychemotherapy (SHR = 1.69) showed elevated relative risks. Conclusion This large multicenter retrospective study shows that there exist a large treatment heterogeneity in advanced MF/SS and differences between USA and non-USA centers but these were not related to survival, while our data reveal that chemotherapy as first treatment is associated with a higher risk of death and/or change of therapy and thus other therapeutic options should be preferable as first treatment approach

Role of stem cell transplantation in treatment of primary cutaneous T-cell lymphoma

Background. Within the heterogeneous group of cutaneous T-cell lymphomas (CTCL) the therapeutic options for advanced and progressive forms are particularly limited. Objective. The therapeutic value of hematopoietic stem cell transplantation in CTCL was analyzed. Material and methods. A literature search using the keywords hematopoietic stem cell transplantation and cutaneous T-cell lymphoma was performed in PubMed. Studies between 1990 and 2017 were taken into account. The studies identified were analyzed for relevance and being up to date. Results. After reviewing the currently available literature no prospective randomized studies were found. Wu et al. showed a superiority of allogeneic transplantation in a comparison of autologous and allogeneic stem cell transplantation for cutaneous lymphoma. The graft-versus-lymphoma effect plays a significant role in a prolonged progression-free survival after allogeneic transplantation. By using a non-myeloablative conditioning regimen, stem cell transplantation can also be an option for elderly patients. The most extensive long-term data after allogeneic stem cell transplantation were reported by Duarte et al. in 2014. Conclusion. Autologous stem cell transplantation does not currently represent a therapeutic option, whereas allogeneic stem cell transplantation for advanced cutaneous T-cell lymphoma, using a non-myeloablative conditioning scheme, does represent a therapeutic option. However, there is no consensus on the appropriate patients and the right timing. Morbidity and mortality of complications should be taken into account. Thus, this procedure is currently subject to an individual case decision

Brentuximab vedotin in CD30(+) cutaneous lymphoma: How do we treat, how shall we treat? A review of the literature

Brentuximab vedotin is an antibody-drug conjugate that brings the antimicrotubule agent monomethyl auristatin E into CD30-expressing cells. Some prior studies demonstrated good efficacy in cutaneous lymphomas. The standard therapeutic scheme is 18 mg kg(-1) every 3 weeks. The background of this work is the fact that cutaneous lymphoma has a different pathophysiology and a dynamic other than systemic lymphomas. The objectives of this review were to get an overview of the currently used therapeutic regimen, and to check whether dose reduction or modified time intervals could be of benefit in a similar way with less toxicity. Therefore, we conducted a systematic review of the literature indexed in PubMed and the Cochrane Central Register of Controlled Trials up to April 2016. The procedure was based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria. The review showed that the currently used therapeutic regimen is 18 mg kg(-1) every 3 weeks. No publications of dose-finding studies in CD30(+) cutaneous T-cell lymphoma (CTCL) were found. Two cases of patients, treated with a dose < 18 mg kg(-1), have been published. Brentuximab vedotin seems to be a powerful treatment option in refractory CD30(+) CTCL, and there is a trend that dose reductions, as well as prolonged treatment intervals, work without any loss of response and with fewer side-effects. What's already known about this topic? Brentuximab vedotin, a Food and Drug Administration-approved drug for the treatment of refractory Hodgkin lymphoma and refractory systemic anaplastic large-cell lymphoma, also shows a good efficacy in CD30(+) cutaneous T-cell lymphoma. The standard therapeutic scheme is 18 mg kg(-1) every 3 weeks. What does this study add? This review indicates that modified therapy protocols with lower doses or less frequent dosing schedules may be effective and reduce side-effects like peripheral neuropathy. Linked Comment: Scarisbrick. Br J Dermatol 2017; 177:1474-1475

Molecular Diagnostics in cutaneous T-Cell Lymphomas - Identification of new potentially therapy-relevant Biomarkers

Hain C, Cieslak C, Mentz A, Stranzenbach R, Kalinowski J, Stadler R. Molekulare Diagnostik bei kutanen T-Zell Lymphomen – Identifizierung neuer potentiell therapierelevanter Biomarke. JOURNAL DER DEUTSCHEN DERMATOLOGISCHEN GESELLSCHAFT. 2019;17(Suppl. 1):1

Developments in the understanding of blood involvement and stage in mycosis fungoides/Sezary syndrome

Dermatology-oncolog

Blood classification and blood response criteria in mycosis fungoides and Sezary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force

Our current mycosis fungoides (MF) and Sezary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sezary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the 'global response' used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry.No large study comparing blood-class as defined by Sezary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p = 1000/mu L plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known. (C) 2018 The Authors. Published by Elsevier Ltd

Blood classification and blood response criteria in mycosis fungoides and Sézary syndrome using flow cytometry: recommendations from the EORTC cutaneous lymphoma task force

Our current mycosis fungoides (MF) and Sézary Syndrome (SS) staging system includes blood-classification from B0-B2 for patch/plaque/tumour or erythroderma based on manual Sézary counts but results from our EORTC survey confirm these are rarely performed in patch/plaque/tumour MF, and there is a trend towards using flow cytometry to measure blood-class. Accurately assigning blood-class effects overall stage and the ‘global response’ used to measure treatment responses in MF/SS and hence impacts management. The EORTC Cutaneous Lymphoma Task Force Committee have reviewed the literature and held a Workshop (June 2017) to agree a definition of blood-class according to flow cytometry. No large study comparing blood-class as defined by Sézary count with flow cytometry has been performed in MF/SS. The definition of blood-class by flow cytometry varies between publications. Low-level blood involvement occurs in patch/plaque/tumour much less than erythroderma (p &lt; 0.001). The prognostic relevance of blood involvement (B1 or B2) in patch/plaque/tumour is not known. Studies have not shown a statistically worse difference in prognosis in erythrodermic MF patients with low-level blood involvement (IIIB) versus those without (IIIA), but Sezary patients who by definition have a leukaemic blood picture (staged IVA1 or higher) have a worse prognosis. For consistency flow, definition for blood-class must be an objective measurement. We propose absolute counts of either CD4+CD7-or CD4+CD26-where B0&lt;250/μL, B1 = 250/μl–&lt;1000/μL and B2≥1000/μL plus a T-cell blood clone. Fluctuations between B0 and B1 should not be considered in the treatment response criteria until further prognostic information is known. © 2018 The Author