Effectiveness of mogamulizumab in patients with Mycosis Fungoides or Sézary syndrome: A multicentre, retrospective, real-world French study.

BACKGROUND: Efficacy and safety of mogamulizumab, a monoclonal antibody directed against C-C chemokine receptor 4, were demonstrated in a previous multinational clinical trial conducted in patients with previously treated cutaneous T-cell lymphoma (CTCL): Sézary syndrome (SS) or Mycosis Fungoides (MF). OBJECTIVES: The real-world French OMEGA study aimed to describe effectiveness and tolerability of mogamulizumab in adult patients with CTCL, overall and according to the disease (SS or MF). METHODS: In this retrospective study, patients treated with mogamulizumab for SS or MF were included from 14 French expert centres. The overall response rate (ORR) under treatment was described (primary criterion), as well as treatment use and safety data. RESULTS: The 122 analysed patients (69 SS, 53 MF) were aged 66.6 ± 12.1 years at mogamulizumab initiation, and their median disease duration was 2.5 years (IQR: 1.3-5.6). Prior to treatment start, they received a median of three systemic CTCL therapies (2-5). Overall, 77.8% of patients suffered from advanced disease (Stage IIB-IVB), with frequent blood (B1/B2) involvement (67.5%). Over the treatment period (median: 4.6 months, 2.1-7.2), 96.7% of patients received all the planned mogamulizumab infusions. Among the 109 patients evaluable for effectiveness, ORR was 58.7% (95% CI [48.9-68.1]) overall, 69.5% [56.1-80.8] in SS and 46.0% [31.8-60.7] in MF. Compartmental response in the blood was observed in 81.8% [69.1-90.9] of SS patients. Skin responses were observed in 57.0% [47.0-66.5] of patients overall, 66.7% [52.9-78.6] in SS and 46.0% [31.8-60.7] in MF. The most common serious adverse drug reactions were rash (8.1% of patients) and infusion-related reactions (2.4%) which led to treatment discontinuation in 7.3% and 0.8% of patients, respectively. One patient with SS died from mogamulizumab-related tumour lysis syndrome. CONCLUSIONS: This large French study confirmed the effectiveness and tolerability of mogamulizumab in SS and MF patients in routine medical practice.

[Stage III melanoma: Sentinel node biopsy, completion lymph node dissection and prospects of adjuvant therapy. A French national survey on current and envisaged practices]. / Mélanome au stade ganglionnaire : analyse du ganglion sentinelle, curage ganglionnaire, perspective des traitements adjuvants. Enquête nationale française sur les pratiques actuelles et envisagées.

BACKGROUND: The recent publication of randomized trials investigating the efficacy of adjuvant therapy and completion lymph node dissection at microscopic stage III melanoma calls for a reappraisal of melanoma management from different angles: indications for sentinel lymph node biopsy, indications for completion lymph node dissection in microscopic-stage disease, and adjuvant therapies. Our objective was to evaluate current practices and to question French onco-dermatologists about any changes they envisaged in their practices in the light of recent publications. METHODS: We conducted a national survey among members of the Cutaneous Oncology Group of the French Society of Dermatology in October 2017. RESULTS: Forty French health centers were included, and 53 individual responses were collected. Sentinel lymph node biopsy for melanoma was performed at 75 % of the centers. Before the summer of 2017 and the publication of MSLT-II (proving the absence of any therapeutic benefits for complete lymph node dissection in microscopic stage III melanoma), when a positive sentinel lymph node was diagnosed, immediate completion lymph node dissection was performed at 90 % of the centers. After the publication of MSLT-II, 45 % of the respondents considered stopping this practice. The risk-benefit ratio prompted prescription of nivolumab and of combined dabrafenib+trametinib as adjuvant therapy by respectively 96 % and 79 % of respondents, while the corresponding rates for interferon and ipilimumab were only 21 % and 15 %. CONCLUSION: Early melanoma management stands on the verge of major changes thanks to the arrival of efficient adjuvant therapies and a decrease in immediate completion lymph node dissections for patients with microscopic stage III is also anticipated.

[Total skin electron beam therapy for early-stage mycosis fungoides: immediate results and long-term follow-up in 68 patients]. / Electronthérapie corporelle totale du mycosis fongoïde aux stades précoces: 68 cas.

BACKGROUND: Our aim was to evaluate the efficacy of total skin electron beam therapy (TSEB) in the management of early-stage mycosis fungoides in order to assess its position in relation to other skin-directed therapies. PATIENTS AND METHODS: A retrospective study of 68 patients (30 in stage T1 and 38 in stage T2). RESULTS: The median treatment duration was 6 weeks. Three months after the end of TSEB, a complete clinical response occurred in 66 patients (97%). The most marked effects of acute toxicity included localized ulcerations in 13 patients (13.2%) not requiring hospitalization. Mean follow-up was 6.5 years (1.6 to 28.7). The overall survival rates at 5 and 10 years were 86% and 71%, respectively. Thirty-nine patients (57.4%) experienced relapse with a mean disease-free interval of 1.8 years. The disease-free survival rates at 5 and 10 years were 41% and 31%, respectively. This rate was higher when TSEB was performed early (p=0.031). Twenty-one years after TSEB, only one case of cutaneous malignancy (basal cell carcinoma) was noted. DISCUSSION: Because of its high response rates and rapidity of action, TSEB should be considered as first-line therapy in the management of early-stage mycosis fungoides.

[Immediate patent blue-induced hypersensitivity during sentinel node detection: The value of cutaneous tests]. / Hypersensibilité immédiate après injection de bleu patenté lors du repérage du ganglion sentinelle : intérêt des tests cutanés.

BACKGROUND: Patent blue is a blue dye commonly used for sentinel node detection in the management of melanoma and breast cancer. Immediate hypersensitivity reactions to patent blue such as blue urticaria, bronchospasm or anaphylactic shock are not rare, being seen in 0.8 to 2.8% of patent blue-treated patients. PATIENTS AND METHODS: We report three cases of anaphylactic shock and two cases of urticaria developed after injection of patent blue in the context of sentinel node detection in breast cancer patients. Immediately after surgery, two patients developed generalized urticaria followed by circulatory collapse requiring resuscitation. The third patient presented massive anaphylactic shock without cutaneous or respiratory signs. Blue urticaria without haemodynamic disturbance was seen in the latter two patients. Prick tests using patent blue were positive for the three patients with positive intradermal reactions (1/10,000 dilution) in all patients. DISCUSSION: These observations underline the severity of patent blue-induced shocks with delayed onset, since they are often observed at the end of surgery. While the mode of sensitization is poorly understood, food and textile dyes are thought to play a role. Skin prick tests provide a simple and reliable method of diagnosing these events. There is a real risk of late anaphylactic shock during sentinel node detection using patent blue and discussion is needed concerning alternative methods of sentinel node detection.