Maladie de Rosai-Dorfman cutanée pure (étude rétrospective de six cas)

DIJON-BU Médecine Pharmacie (212312103) / SudocSudocFranceF

Infection cutanée à scedosporium apiospermum au cours d'un traitement par anti-TNF alpha

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Posaconazole (une alternative thérapeutique dans la prise en charge des mucormycoses?)

DIJON-BU Médecine Pharmacie (212312103) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Management of adjuvant settings for Stage III melanoma patients in France prior to checkpoint inhibitors: epidemiological data from the RIC-Mel database

International audienceBackground: Targeted therapies such as BRAF and MEK inhibitors and immunotherapies have been made available to treat melanoma.Objectives: To provide an overview of the management of the French Stage III melanoma population after complete lymph node resection prior to new adjuvant therapies.Materials and methods: A subgroup data analysis.Results: Data from 1,835 patients were analysed (15.58% Stage IIIA, 39.24% Stage IIIB, 43.92% Stage IIIC and 1.25% Stage IIID). Superficial spreading melanoma was the most frequent (70.98% in Stage IIIA for whom mutation analysis was performed; BRAF mutation was identified in up to 62% Stage IIIA patients). Sentinel lymph node biopsy was performed in 88.46% of Stage IIIA patients, 42.36% of Stage IIIB, 53.97% of Stage IIIC and 34.78% of Stage IIID. Up to 80% of Stage IIIA patients had no adjuvant treatment follow-up. Ulceration (p = 0.004; RR: 2.98; 95% CI: 1.4-6.3) and age at diagnosis (p = 0.0002; RR: 1.04; 95% CI: 1.02-1.06) were significant predictive factors for survival. Adjuvant interferon-α was administered in up to 13.04% of Stage IIID patients.Conclusion: Only a small number of Stage III melanoma patients were treated with interferon-α in adjuvant settings. New adjuvant therapies are currently having an effect on clinical practice in France, increasing survival and decreasing cost

Efficacy, safety and factors associated with disease progression in patients with unresectable (stage III) or distant metastatic (stage IV) BRAF V600-mutant melanoma: An open label, non-randomized, phase IIIb study of trametinib in combination with dabrafenib

International audienceBackground: BRAF and MEK inhibitors combination, including dabrafenib (D) and trametinib (T) have transformed the treatment of BRAF V600-mutant advanced melanoma patients, including patients with brain metastasis (BM). In a large phase IIIb, single-arm, open-label, multicenter French study, we assessed safety, response to treatment, progression-free survival (PFS) and factors associated with progression, and stratified the population into risk groups. Methods: Patients with unresectable, advanced, BRAF V600-mutant melanoma were included, including those with the presence of BM, Eastern Cooperative Oncology Group Performance Status (ECOG PS) ≤2, elevated lactate dehydrogenase (LDH) or previous melanoma treatments. Responses were determined locally, without central review. PFS was estimated using the Kaplan–Meier analysis and modelled with multivariate Cox model. Risk subgroups were identified using a regression tree analysis. Results: Between March 2015 and November 2016, 856 patients received at least one D + T dose. Overall, 92% had stage IV melanoma, 38% ECOG PS ≥1, 32% BM and 37.5% elevated LDH. Median PFS was 8.02 months (95% confidence interval [CI] 7.33–8.77). Significant factors associated with lower PFS were ECOG PS ≥1, elevated LDH, ≥3 metastatic sites and presence of BM. Patients with <3 metastatic sites, ECOG = 0 and no BM had the highest probability of PFS at 6 months (83%, 95% CI 76–87) and 12 months (56%, 95% CI 47–64), respectively. Conclusions: This is the largest prospective study in advanced BRAF V600-mutant melanoma patients treated with D + T, conducted in conditions close to ‘real-world practice’. We confirm previous findings that LDH, ECOG PS and ≥3 metastatic sites are associated with shorter PFS, but the real-world setting introduces BM as a major prognostic factor

Late-onset adverse events of anti-PD1 therapy in melanoma patients: An observational study from MELBASE, a nationwide prospective cohort

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Differential gradients of immunotherapy vs targeted therapy efficacy according to the sun-exposure pattern of the site of occurrence of primary melanoma: a multicenter prospective cohort study (MelBase)

International audienceBackground The tumor mutational burden (TMB) is high in melanomas owing to UV-induced oncogenesis. While a high TMB is a predictive biomarker of response to PD-1 inhibitors, it may be associated with the rise of resistant clones to targeted therapy over time. We hypothesized that survivals may depend on both the sun-exposure profile of the site of primary melanoma and the type of systemic treatment. Patients and methods Patients were screened from MelBase, a multicenter biobank dedicated to the prospective follow-up of stage III/IV melanoma. All patients with a known cutaneous primary melanoma who received a 1st-line systemic treatment by immunotherapy or targeted therapy were included (2013-2019). Outcomes were progression-free survival (PFS) and overall survival (OS). Results 973 patients received either anti PD-1(n=466), anti CTLA-4(n=143), a combination of both (n=118), or targeted therapies (n=246). Patients’ characteristics at treatment initiation were: male (62%), median age of 62, AJCC stage IV (84%). Median follow-up was 15.5 months. The primary melanoma was located on chronically sun-exposed skin in 202 patients (G1: head neck), on intermittently sun-exposed skin in 699 patients (G2: trunk, arms, legs), and on sun-protected areas in 72 patients (G3: palms, soles). Median PFS was significantly higher in G1 under anti PD-1 treatment (8.7 months vs 3.3 and 3.4 months for G2 and G3, respectively) (p=0.011). PFS did not significantly differ in other groups. Similarly, median OS was significantly higher in G1 receiving 1 st line anti PD-1 treatment (45.6 months vs 31.6 and 21.4 months for G2 and G3) (p=0.04), as opposed to 1 st line targeted therapy (19.5 months vs 16.3 and 21.1 months for G1, G2 and G3 respectively). Conclusion Our study confirms that immunotherapy with anti PD-1 is particularly recommended for melanomas originating from chronically sun-exposed areas, but this finding needs to be confirmed by further research

Effectiveness and safety of nivolumab in patients with advanced melanoma: A multicenter, observational study

International audienceThis retrospective observational study aimed to determine the effectiveness, safety and patterns of the use of nivolumab in patients with advanced melanoma in real-world clinical practice in France using data from a Temporary Authorization for Use Program (ATU). Data were collected from patients with unresectable or metastatic melanoma enrolled in a French national database (Réseau pour la Recherche et l'Investigation Clinique sur le Mélanome: Ric-Mel) and treated with nivolumab during the ATU program (12 September 2014 to 31 August 2015). The primary objectives of the study were to evaluate the effect of patient characteristics on clinical response and overall survival (OS). Among 400 included patients (median age 66 years), the majority (83%) received nivolumab as second- or subsequent-line therapy. The median durations of progression-free survival and OS were 3.3 and 14.1 months, respectively, and 31.6% of patients achieved an objective response with a median duration of 20.1 months (range: 0-34.7). The safety profile of nivolumab was manageable and consistent with those of previous clinical trials, with an incidence of grade 3-5 adverse events of 13.8%. The safety and effectiveness of nivolumab in patients with advanced melanoma in real-world clinical practice in France were in line with the data reported in the Phase 3 trials CheckMate 066 and 037 of nivolumab in this patient population