EORTC consensus recommendations for the treatment of mycosis fungoides/Sézary syndrome - Update 2023.

On behalf of the EORTC Cutaneous Lymphoma Tumours Group (EORTC-CLTG) and following up on earlier versions published in 2006 and 2017 this document provides an updated standard for the treatment of mycosis fungoides and Sézary syndrome (MF/SS). It considers recent relevant publications and treatment options introduced into clinical practice after 2017. Consensus was established among the authors through a series of consecutive consultations in writing and a round of discussion. Treatment options are assigned to each disease stage and, whenever possible and clinically useful, separated into first- and second line options annotated with levels of evidence. Major changes to the previous version include the incorporation of chlormethine, brentuximab vedotin, and mogamulizumab, recommendations on the use of pegylated interferon α (after withdrawal of recombinant unpegylated interferons), and the addition of paragraphs on supportive therapy and on the care of older patients. Still, skin-directed therapies are the most appropriate option for early-stage MF and most patients have a normal life expectancy but may suffer morbidity and impaired quality of life. In advanced disease treatment options have expanded recently. Most patients receive multiple consecutive therapies with treatments often having a relatively short duration of response. For those patients prognosis is still poor and only for a highly selected subset long term remission can be achieved with allogeneic stem cell transplantation. Understanding of the disease, its epidemiology and clinical course, and its most appropriate management are gradually advancing, and there is well-founded hope that this will lead to further improvements in the care of patients with MF/SS.

[Quality of life of patients with mycosis fungoides and Sézary syndrome]. / Lebensqualität von Patienten mit Mycosis fungoides und Sézary-Syndrom.

Mycosis fungoides as the most common type and Sézary syndrome as a leukemic variant belong to the rare group of cutaneous T­cell lymphomas. Both diseases are considered incurable and show a chronic course. Since there is no curative treatment, maintaining quality of life and relief of symptoms should be important elements when treating patients with mycosis fungoides and Sézary syndrome. Pruritus, which is a common and burdensome symptom of cutaneous T­cell lymphoma, may negatively impact quality of life. Pruritus and quality of life can be assessed with established measurement tools. Consistent recording enables physicians to recognize restrictions in physical and psychosocial aspects of quality of life early so that therapy can be adapted.

Chlormethin-Gel zur Behandlung der Mycosis fungoides: Ein Expertenkonsens aus Deutschland, Österreich und der Schweiz (DACH-Region) zum Therapiemanagement.

HINTERGRUND: Chlormethin-Gel ist in Europa zur Therapie von Patienten mit Mycosis fungoides in allen Krankheitsstadien zugelassen. Die optimalen Behandlungsregime hinsichtlich Frequenz, Dosierung, Kombinations- oder Erhaltungstherapien sind noch nicht vollständig etabliert. METHODIK: Zehn in der Erforschung und Behandlung kutaner T-Zell-Lymphome erfahrene Experten aus Deutschland, Österreich und der Schweiz (DACH-Region) wurden schriftlich zu Indikation, Anwendungsfrequenz, Beurteilung des Therapieerfolgs, Begleittherapie, Nebenwirkungen, Kombinationstherapien in späteren Krankheitsstadien, Erhaltungstherapie und Adhärenz im Rahmen der Therapie der Mycosis fungoides mit Chlormethin-Gel befragt. Die strukturiert aufbereiteten Ergebnisse der Umfrage wurden in einer Konsensuskonferenz diskutiert und Empfehlungen zum Management der Therapie mit Chlormethin-Gel entwickelt. ERGEBNISSE: Wesentlich für die Therapie mit Chlormethin-Gel ist ein individuelles, symptomorientiertes Therapiemanagement. Systemische Nebenwirkungen des Wirkstoffs sind wegen der fehlenden systemischen Verfügbarkeit bei topischer Anwendung unwahrscheinlich. Die häufig auftretende allergische oder irritativ-toxische Kontaktdermatitis kann durch eine Anpassung des Therapieregimes, Therapiepausen sowie nebenwirkungsspezifische und unterstützende Maßnahmen häufig beherrscht werden. Ein einschleichender Therapiebeginn mit Anwendung von Chlormethin-Gel jeden zweiten Tag kann die Tolerabilität wesentlich verbessern, insbesondere wenn die Therapie alternierend mit topischen Kortikosteroiden erfolgt. SCHLUSSFOLGERUNGEN: Die Anwendung von Chlormethin-Gel bei Mycosis fungoides wird durch die begleitende Kontaktdermatitis häufig eingeschränkt. Mit einem geeigneten Therapie- und Nebenwirkungsmanagement können vermeidbare Therapieabbrüche verhindert werden und mehr Patienten von der Therapie profitieren.

The optimal use of chlormethine gel for mycosis fungoides: An expert consensus from Germany, Austria and Switzerland (DACH region).

BACKGROUND: In Europe chlormethine gel is licensed for the management of patients with mycosis fungoides of all stages. However, the optimal regimen regarding frequency and dosing as well as combination and maintenance therapy is not well established. METHODS: Ten experts experienced in research and management of cutaneous T-cell lymphomas from Germany, Austria, and Switzerland (DACH region) were asked in written form to report on indication for chlormethine gel, frequency of use, monitoring, concomitant therapies, adverse effects, combination therapies in later stages of the disease, maintenance therapy, and adherence to this therapy for mycosis fungoides. The structured answers were discussed in a consensus conference and recommendations were developed. RESULTS: Essential for therapy with chlormethine gel is an individualized and symptom-oriented management. Because of the lack of systemic resorption of topically administered chlormethine gel, systemic adverse events are unlikely. An allergic or irritative-toxic contact dermatitis is common but manageable with adaptation of the regimen, interruption of administration, and symptom-specific supportive measurements. A step-up initial approach with application of chlormethine gel every other day is associated with a better tolerability, especially if it is alternated with topical corticosteroids. CONCLUSIONS: The use of chlormethine gel in the management of mycosis fungoides is often limited by a concomitant contact dermatitis. An adequate therapeutic regimen and the management of adverse effects can preclude an unnecessary withdrawal of therapy so that more patients can benefit from this treatment option.

Clinical Outcomes of Advanced-Stage Cutaneous Lymphoma under Low-Dose Gemcitabine Treatment: Real-Life Data from the German Cutaneous Lymphoma Network.

BACKGROUND: Gemcitabine is an effective single-agent chemotherapy used in advanced stages of cutaneous T-cell lymphoma (CTCL). However, gemcitabine used in the current standard regimen is frequently associated with adverse events (AE), such as an increased risk for myelosuppression and severe infections. OBJECTIVES: We investigated in this retrospective study the effect of low-dose gemcitabine in pretreated advanced-stage CTCL and in blastic plasmacytoid dendritic cell neoplasia (BPDCN) regarding overall response (OR), progression-free survival (PFS), and AE. MATERIAL AND METHODS: A retrospective, multicenter study was conducted on 64 CTCL and BPDCN patients treated with gemcitabine in average absolute dosage of 1,800 mg/m2 per cycle, which is 50% lower compared to standard dosage of 3,600 mg/m2 per cycle (1,200 mg/m2 day 1, 8, 15). Evaluation of response to therapy and AE was done 4-6 weeks after the sixth cycle. RESULTS: OR was 62% with 11% demonstrating a complete response. The median time of PFS was 12 months and median time to next treatment was 7 months. Only 3/63 patients showed serious side effects, e.g., port infection or acute renal failure. Almost 73% of the patients experienced minor to moderate side effects (CTCAE grade 0-2). Fatigue (27.2%), fever (22.7%), and mild blood count alteration (18.2%) were the most common AE. CONCLUSIONS: This retrospective analysis supports the use of low-dose gemcitabine therapy in CTCL, demonstrating with 62% OR and PFS of 12 months an almost identical response rate and survival as compared to the standard dose therapy reported in previous studies but with a significantly improved safety profile and tolerability.

Reconstruction of Full Thickness Defects on the Scalp With Artificial Dermal Regeneration Template: Analysis of Long-Term Results in 68 Cases.

BACKGROUND: Artificial skin substitute templates have been shown to be a reliable solution for the reconstruction of large scalp defects with exposed skull bone, but there is a lack of long-term data. OBJECTIVE: The aim of this retrospective study was to investigate the long-term outcome of the procedure in a large cohort of 68 cases. MATERIALS AND METHODS: In total, 58 patients with 68 full thickness scalp defects with exposed skull bone, were included. Mean follow-up time was 24 (±19) months. RESULTS: The mean size of the defects was 63 (±54) cm2. During the follow-up period, no local recurrences occurred. Complications were observed in 13% of the cases including template necrosis (4%), infections (4%), ulcerations (3%), and autograft necrosis (2%). During the final follow-up, 26 patients had died due to internal diseases not associated with the surgery. Cosmetic results were rated good by the patients and an independent observer. CONCLUSION: The use of a dermal regeneration template for the reconstruction of large, full thickness defects of the scalp with exposed skull bone is a reliable method regarding the complication rate, safety of the procedure, and cosmetic outcome. Limitations of this study are the retrospective and single center design.

Primary cutaneous diffuse large B-cell lymphoma, NOS and leg type: Clinical, morphologic and prognostic differences.

BACKGROUND AND OBJECTIVES: Primary cutaneous diffuse large B-cell lymphoma, NOS (PCLBCL/NOS) is a rare PCLBCL. Only few data are available for this tumor. The aim of this study was to identify clinical and/or immunohistochemical markers (in addition to Bcl-2) that characterize PCLBCL/NOS, assist in differentiating it from PCLBCL, leg type (PCLBCL/LT) and help to assess the clinical course/prognosis. PATIENTS AND METHODS: Bcl-2- PCLBCL/NOS) cases (n = 14 were compared with Bcl-2+ PCLBCL/LT cases (n = 29). RESULTS: PCLBCL/NOS patients were younger, predominantly male and had better survival rates than patients with PCLBCL/LT. Patients with PCLBCL/NOS presented more often with larger plaques limited to one or two contiguous body regions, whereas PCLBCL/LT cases often presented with disseminated lesions. Neoplastic cells had a higher proliferation rate (Ki67) in PCLBCL/LT patients. The tumor microenvironment of PCLBCL/NOS had a more prominent CD3+ infiltrate. Overall survival data for the whole cohort (n = 37) revealed that female gender and Bcl-2 expression correlated with a worse survival rate. Bcl-6 expression and centroblastic subtype correlated with better outcomes. None of the other markers studied (e.g. GCB/non-GCB subtype) correlated with survival rate. CONCLUSIONS: PCLBCL/NOS and PCLBCL/LT differ in their clinical behavior and outcomes. Bcl-2 still seems to be the best marker for discriminating between these two subgroups. Bcl-2, female gender and Bcl-6 represent prognostic markers for PCLBCL.

[Single-center retrospective analysis of extracorporal photopheresis in clinical practice : Peripheral venous compared to central venous access]. / Unizentrische, retrospektive Analyse der praktischen Durchführung der extrakorporalen Photopherese : Periphervenöser und zentralvenöser Zugang im Vergleich.

BACKGROUND: Extracorporal photopheresis (ECP) was shown to be effective without severe side effects in the treatment of cutaneous T cell lymphoma (CTCL) and graft versus host disease (GvHD). However, only few studies investigated the practical aspects of ECP. METHODS: Treatment protocols of 2038 ECP procedures in 52 patients (CTCL, n = 29; GvHD, n = 15; other, n = 8) were evaluated. The patients were treated with the UVAR® XTS™ ECP system (Therakos, Inc. Johnson & Johnson, Raritan, NJ, USA) between 2001 and 2010. All patients started with a peripheral venous access. During the course of treatment 7 patients were treated via a port and 4 via a central venous catheter. RESULTS: In all, 1765 (86.6%) treatments were performed with a peripheral venous access; 239 (11.7%) ECPs were done via a port and 34 (1.7%) via a central venous catheter. The peripheral venous access showed a higher flow rate and longer photoactivation time. ECPs via port lead to higher UV-irradiated volumes, longer treatment times and higher differences in systolic blood pressure. The following side effects were observed: being unwell (n = 13), hypo- (n = 13) and hypertension (n = 7), vertigo (n = 4), headache (n = 4), shortness of breath (n = 4), fever (n = 3) and metallic taste (n = 3). Technical complications such as problems with venous access (9.6%) occurred in 385 (18.9%) treatments. CONCLUSIONS: Peripheral venous access should be preferred for ECP treatments.