Real-life efficacy of immunotherapy for Sézary syndrome: a multicenter observational cohort study.

Background: Sézary syndrome is an extremely rare and fatal cutaneous T-cell lymphoma (CTCL). Mogamulizumab, an anti-CCR4 monoclonal antibody, has recently been associated with increased progression-free survival in a randomized clinical trial in CTCL. We aimed to evaluate OS and prognostic factors in Sézary syndrome, including treatment with mogamulizumab, in a real-life setting. Methods: Data from patients with Sézary (ISCL/EORTC stage IV) and pre-Sézary (stage IIIB) syndrome diagnosed from 2000 to 2020 were obtained from 24 centers in Europe. Age, disease stage, plasma lactate dehydrogenases levels, blood eosinophilia at diagnosis, large-cell transformation and treatment received were analyzed in a multivariable Cox proportional hazard ratio model. This study has been registered in ClinicalTrials (SURPASSe01 study: NCT05206045). Findings: Three hundred and thirty-nine patients were included (58% men, median age at diagnosis of 70 years, Q1-Q3, 61-79): 33 pre-Sézary (9.7% of 339), 296 Sézary syndrome (87.3%), of whom 10 (2.9%) had large-cell transformation. One hundred and ten patients received mogamulizumab. Median follow-up was 58 months (95% confidence interval [CI], 53-68). OS was 46.5% (95% CI, 40.6%-53.3%) at 5 years. Multivariable analysis showed that age ≥ 80 versus <50 (HR: 4.9, 95% CI, 2.1-11.2, p = 0.001), and large-cell transformation (HR: 2.8, 95% CI, 1.6-5.1, p = 0.001) were independent and significant factors associated with reduced OS. Mogamulizumab treatment was significantly associated with decreased mortality (HR: 0.34, 95% CI, 0.15-0.80, p = 0.013). Interpretation: Treatment with mogamulizumab was significantly and independently associated with decreased mortality in Sézary syndrome. Funding: French Society of Dermatology, Swiss National Science Foundation (IZLIZ3_200253/1) and SKINTEGRITY.CH collaborative research program.

Radiotherapy and prognostic factors in adnexal carcinomas: A retrospective study of 657 patients from the French CARADERM network.

BACKGROUND: Cutaneous adnexal carcinomas are a heterogeneous group of rare neoplasms. Surgical excision is the first-line treatment in localized stage. The use and effectiveness of radiotherapy have not been thoroughly evaluated in these neoplasms. OBJECTIVES: The present work analyses prognostic factors on outcomes in skin adnexal carcinomas, based on data from the CARADERM (CAncers RAres DERMatologiques) database. METHODS: Data were collected retrospectively including demographic data, tumour types and therapeutic characteristics of all patients included in the CARADERM database, with at least one informative follow-up visit. Analyses were performed on three populations: patients with complete resection of the primary tumour (ADJ/primary population), patients achieving complete remission after complete resection of a recurrent tumour (ADJ/recurrent population) and patients with unresectable locally advanced or metastatic tumours (ADV/MET population). Overall and recurrence/progression-free survivals at 3-year were analysed using Cox regression models. RESULTS: Radiotherapy did not affect overall survival (OS) in the ADJ/primary population. Adjusted recurrence-free survival (RFS) was significantly lower in the radiotherapy group in ADJ/primary group. Older patients had significantly poorer OS and RFS. Tumour size and immunosuppression were significantly associated with poorer RFS only. Radiotherapy had no effect on OS and RFS in the ADJ/recurrent population. Age was the only factor associated with a poorer OS. Radiotherapy was significantly associated with longer progression-free survival (PFS) in age-sex adjusted analysis in the ADV/MET population, without effect on OS. CONCLUSIONS: Our study shows that age, tumour size and immunosuppression are significantly associated with survival in localized adnexal carcinomas. Radiotherapy may improve PFS in the ADV/MET population but not in localized and recurrent carcinomas after complete excision.

Molecularly matched targeted therapy: a promising approach for refractory metastatic melanoma.

BACKGROUND: Only a fraction of patients with metastatic melanoma derive durable benefit from approved treatments. The clinical impact of personalized medicine strategies for melanoma, apart from BRAF, NRAS, or CKIT targeting, has rarely been reported. MATERIALS AND METHODS: By means of the Group of Cutaneous Oncology of the French Society of Dermatology, we retrospectively included all patients with advanced melanoma aged 18 years and older for whom molecular testing identified one or more actionable molecular alterations and who accordingly received molecularly matched therapy. We excluded patients with only BRAF, NRAS, or CKIT alterations and patients who received molecularly matched therapy for less than 15 days. RESULTS: We included 26 patients with a median follow-up of 8 months (1-54), a median age of 63 years (24-89), and a sex ratio of 2.7. These patients had been heavily pretreated, and 64% had elevated LDH levels. The disease control rate was 38%, with 4 cases of partial response (overall response rate: 15%) and 6 of stable disease for at least 6 months. The median duration of treatment was 3.1 months (0.9-13.5). Among patients with disease control, the median duration of control was 6.6 months (2.6-13.5) and 3 cases were ongoing at the end of the study. Patients with controlled disease had GNA11, MAP2K1, FYCO1-RAF1, HRAS, ATM, CCND1, MDM2/CDK4, and CDKN2A/NRAS alterations. CONCLUSIONS: High-throughput sequencing followed by matched targeted therapy is a promising approach for patients with advanced melanoma refractory to approved treatments.

Combined Nivolumab and Ipilimumab in Octogenarian and Nonagenarian Melanoma Patients.

Data regarding elderly melanoma patients treated with anti-PD-1 or anti-CTLA-4 antibodies are in favor of tolerability outcomes that are similar to those of younger counterparts. However, there are very few studies focusing on elderly patients receiving nivolumab combined with ipilimumab (NIVO + IPI). Here, we ask what are the current prescribing patterns of NIVO + IPI in the very elderly population and analyze the tolerance profile. This French multicenter retrospective study was conducted on 60 melanoma patients aged 80 years and older treated with NIVO + IPI between January 2011 and June 2022. The mean age at first NIVO + IPI administration was 83.7 years (range: 79.3-93.3 years). Fifty-five patients (92%) were in good general condition and lived at home. Two dosing regimens were used: NIVO 1 mg/kg + IPI 3 mg/kg Q3W (NIVO1 + IPI3) in 27 patients (45%) and NIVO 3 mg/kg + IPI 1 mg/kg Q3W (NIVO3 + IPI1) in 33 patients (55%). NIVO + IPI was a first-line treatment in 39 patients (65%). The global prevalence of immune-related adverse events was 63% (38/60), with 27% (16/60) being of grade 3 or higher. Grade ≥ 3 adverse events were less frequent in patients treated with NIVO3 + IPI1 compared with those treated with NIVO1 + IPI3 (12% versus 44%, p = 0.04). In conclusion, the prescribing patterns of NIVO + IPI in very elderly patients are heterogeneous in terms of the dosing regimen and line of treatment. The safety profile of NIVO + IPI is reassuring; whether or not the low-dose regimen NIVO3 + IPI1 should be preferred over NIVO1 + IPI3 in patients aged 80 years or older remains an open question.

Efficacy of Immune Checkpoint Inhibitor (ICI) Rechallenge in Advanced Melanoma Patients' Responders to a First Course of ICI: A Multicenter National Retrospective Study of the French Group of Skin Cancers (Groupe de Cancérologie Cutanée, GCC).

BACKGROUND: The long-term effectiveness of immune checkpoint inhibitor (ICI) rechallenge for progressive or recurrent advanced melanoma following previous disease control induced by ICI has not been thoroughly described in the literature. PATIENTS AND METHODS: In this retrospective multicenter national real-life study, we enrolled patients who had been rechallenged with an ICI after achieving disease control with a first course of ICI, which was subsequently interrupted. The primary objective was to evaluate tumor response, while the secondary objectives included assessing the safety profile, identifying factors associated with tumor response, and evaluating survival outcomes. RESULTS: A total of 85 patients from 12 centers were included in the study. These patients had advanced (unresectable stage III or stage IV) melanoma that had been previously treated and controlled with a first course of ICI before undergoing rechallenge with ICI. The rechallenge treatments consisted of pembrolizumab (n = 44, 52%), nivolumab (n = 35, 41%), ipilimumab (n = 2, 2%), or ipilimumab plus nivolumab (n = 4, 5%). The best overall response rate was 54%. The best response was a complete response in 30 patients (35%), a partial response in 16 patients (19%), stable disease in 18 patients (21%) and progressive disease in 21 patients (25%). Twenty-eight adverse events (AEs) were reported in 23 patients (27%), including 18 grade 1-2 AEs in 14 patients (16%) and 10 grade 3-4 AEs in nine patients (11%). The median progression-free survival (PFS) was 21 months, and the median overall survival (OS) was not reached at the time of analysis. Patients who received another systemic treatment (chemotherapy, targeted therapy or clinical trial) between the two courses of ICI had a lower response to rechallenge (p = 0.035) and shorter PFS (p = 0.016). CONCLUSION: Rechallenging advanced melanoma patients with ICI after previous disease control induced by these inhibitors resulted in high response rates (54%) and disease control (75%). Therefore, ICI rechallenge should be considered as a relevant therapeutic option.

Genital Pseudotumor as a Manifestation of Mpox Virus Infection.

This case report describes a 37-year-old man with a 1-week history of a genital nodule that rapidly ulcerated and with concomitant fever 2 days after anal intercourse.

Histological Features Associated With Human Mpox Virus Infection in 2022 Outbreak in a Nonendemic Country.

Skin histology of papules and pustules from 5 men having sex with men with mpox infection showed viral intracytoplasmic cytopathic changes, interface dermatitis, marked inflammatory dermic infiltrate including superficial neutrophils and perivascular and periadnexal deep lymphocytes. Histologic description of mpox lesions improves our understanding about clinical presentations and may have some therapeutic implications.

Impact of systemic therapies in metastatic melanoma of unknown primary: A study from MELBASE, a French multicentric prospective cohort.

BACKGROUND: Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied. OBJECTIVE: To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP). METHODS: Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed. RESULTS: Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P = .73 and P = .93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type. LIMITATIONS: No record of standard diagnostic criteria of MUP used in the participating centers. CONCLUSIONS: Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies.