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Sebastien Leruste,1 Mathilde Marx,1 Cassie Ah-Mouck,1 Lindsay Yap-Chim,1 Nathalie Sultan-Bichat,2,3 Marie Beylot-Barry,4 Michel Spodenkiewicz,5,6,* Jessica Dumez,1,6,* Antoine Bertolotti3,6,7 1University Department of General Medicine, Saint-Pierre, La Réunion, France; 2Dermatology department, CH Ouest Réunion, St Paul, La Réunion, France; 3MISOLRE, Prevention Association, Saint-Paul, La Réunion, France; 4Dermatology Department, Saint-André Hospital, Bordeaux University Hospital, INSERM U 1053, Bordeaux, Gironde, France; 5Mental Health Department, Reunion University Hospital Sites South, Saint-Pierre, La Réunion, France; 6Inserm CIC1410, Reunion University Hospital, Saint Pierre, La Réunion, France; 7Infectious Diseases-Dermatology Department, Reunion University Hospital, Saint Pierre, La Réunion, France*These authors contributed equally to this workCorrespondence: Antoine Bertolotti, Inserm CIC1410, Infectious diseases-dermatology department, Reunion University Hospital, 97 av. Président Mitterrand, Saint Pierre, La Réunion, 97448, France, Tel +02 62 35 91 65, Fax +02 62 35 96 51, Email antoine_bertolotti@yahoo.frAbstract: The incidence of melanoma in Reunion Island is on the rise and is now one of the highest worldwide. Although the main risk factor of melanoma is sun exposure during childhood, sun protection measures remain insufficient in Reunionese schools. From November 2019 to November 2020, we conducted a qualitative study to explore the attitudes, barriers, and motivations to sun protection among the main actors of children’s protection in Reunion Island. Individual semi-directive interviews were performed with 14 children aged 6 to 10 years, 13 parents, and 13 teachers. The interviews were recorded and transcribed. Relevant data were coded, triangulated, analyzed, and then modeled following the methodology of grounded theory. Sufficiency of the data was sought. All 40 participants described their sun protection habits. Protection was lower during school activities than during leisure activities. Parents identified several practical and financial barriers to sun protection. Teachers pointed out the lack of adequate infrastructure and sun protection training. Responsibility for children’s protection was a point of disagreement between parents and teachers. Children limited their use of protection, mainly for reasons of comfort. Children’s sun protection in schools is the responsibility of educational staff, parents, and society at large. Improving communication between these various actors is necessary. Sun safety campaigns and reorganization of the school environment would allow for better protection of the child population.Keywords: melanoma, school, environment, preventive medicine and public health, children’s health, sun protection factor

OBJECTIVE: To investigate the nature of polyarthritis in patients with moderate to severe psoriasis undergoing treatment with efalizumab, a humanized anti-CD11a monoclonal antibody. METHODS: In a multicenter study, we retrospectively analyzed patients who developed arthritis during treatment with efalizumab. The relationship between joint manifestations and psoriatic disease was addressed by using different classification criteria for psoriatic arthritis (PsA). The course of arthritis and its response to treatment were also investigated. RESULTS: Sixteen patients developed de novo inflammatory rheumatic disease, with a mean delay of 15 weeks following the start of treatment, and with exclusive asymmetric peripheral monarthritis or oligoarthritis (8 patients), inflammatory spinal disease (1 patient), or both (7 patients), associated in some cases with enthesitis and dactylitis. All patients fulfilled at least 2 different sets of classification criteria for PsA. In most of them, an improvement in skin lesions was observed at the onset of PsA, as measured using the Psoriasis Area and Severity Index (mean score 24.88 before efalizumab versus 18.78 at the time of arthritis). Efalizumab treatment was stopped in 11 patients and was followed by the elimination of rheumatologic symptoms in 1 patient, while 8 patients required treatment with nonsteroidal antiinflammatory drugs with or without methotrexate, with 2 later being switched to tumor necrosis factor alpha inhibitors. Reintroduction of efalizumab (2 patients) was followed by a relapse of PsA. CONCLUSION: This study questions the role of efalizumab in the induction of PsA. It also emphasizes the discrepancy between the courses of psoriatic skin and joint manifestations under treatment. Prospective case-control studies are needed to accurately investigate the impact of efalizumab on PsA. [ABSTRACT FROM AUTHOR]

Immune checkpoint inhibitors (ICIs) present clinicians with the challenge of managing immune-related adverse events (irAEs), which can range from mild to severe due to immune system activation 1 . While guidelines recommend discontinuing ICIs for grade 3 partial and all grade 4 irAEs, there is growing interest in rechallenging patients based on oncological outcomes, particularly for cardiovascular and neurological irAEs where data remains scarce 1,2 . We retrospectively evaluated the safety of ICI rechallenge following grade 3-4 irAEs, specifically focusing on cardiovascular and neurological events, in patients discussed at our multidisciplinary immunotoxicity assessment board between 2019 and 2021. Fifteen patients were included, with a median time to severe irAE onset of 49 days. Among them, five patients experienced neurological adverse events (NAEs): aseptic meningitis (3), inflammatory polyradiculoneuropathy (1), and ophthalmoplegia (1), while one patient presented with myocarditis. Of the 15 patients retreated with ICIs after initial severe irAEs, 11 (73%) remained free of subsequent irAEs, two (13%) experienced recurrence of the initial irAE, and two (13%) developed new irAEs distinct from the initial event. The median time to event recurrence was 69 days, occurring no earlier than the initial severe irAE. In the subset analysis focusing on severe cardiovascular and neurological irAEs, rechallenge with ICIs was generally well tolerated. However, one patient treated with anti-PD1 experienced a relapse of grade 2 aseptic meningitis. Overall, our findings suggest that rechallenging with ICIs after severe irAEs, including those affecting the cardiovascular and neurological systems, may be safe, particularly after irAE regression and corticosteroid withdrawal., Competing Interests: EG: congress fees and investigator for BMS and MSD. RV: speakers’ bureau for BMS. SM-P: consultant on boards for BMS. AP-L: congress fees for BMS. CDu: Clinical investigation in trials, congress fees and member of boards for BMS, MSD. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Eldani, Kostine, Faure, Lazaro, Rigothier, Hiriart, Teulières, Poullenot, Haissaguerre, Zysman, Veillon, Vergnenegre, Issa, Domblides, Mary-Prey, Beylot-Barry, Pham-Ledard, Dutriaux, Sole, Duval and Gerard.)

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&#95;200253/1) and SKINTEGRITY.CH collaborative research program., Competing Interests: AdM declares nonfinancial support from Kyowa Kirin and Recordati Rare Diseases; fees from Takeda, Almirall and Recordati Rare Diseases, and research funding, outside the scope of this study, from Kyowa Kirin, Innate Pharma, Almirall and Takeda. MB declares consultant fees from Innate Pharma, Kyowa Kirin, Takeda, BMS, Sanofi, Quantum Genomics, and research funding from Kyowa Kirin and Takeda, outside the scope of this study. SM declares consultant fees outside the scope of this study, from Pierre Fabre, Sanofi, Novartis and Biocartis, and has received research funding from BMS, Novartis and Roche. NF declares having received nonfinancial support from Kyowa Kirin. PS received a research grant from Pierre Fabre, fees unrelated to this manuscript from Bristol-Myers Squibb, MSD, Merck-Serono, Pfizer, Roche-Genentech, Pierre Fabre, and Novartis; received nonfinancial support from Bristol-Myers Squibb, MSD, Roche-Genentech, Pierre Fabre, and Novartis outside of the scope of this study. MBB declares consultant fees from Kyowa Kirin, Takeda and Recordati and research funding from Kyowa Kirin and Almirall outside the scope of this study. HMT declares consultant fees outside from the scope of this study from Innate Pharma, and has received research funding, outside the scope of this study, from Kyowa Kirin. SIHO consultant fees outside the scope of this study from Takeda and Recordati. GD declares consultant fees outside of the scope of this study from Kyowa Kirin and Recordati. EG declares consultant fees and/or grant support from Mallinckrodt, Helsinn, Takeda, Novartis and Kyowa Kirin unrelated to this work. FG declares consultant fees from Recordati and Kyowa Kirin, outside from the scope of this study. GQ declares consultant fees from Takeda, Recordati and Kyowa Kirin, outside the scope of this study. CM declares nonfinancial support from MSD, Pfizer, Novartis, Bristol-Myers Squibb, Pierre Fabre, Leo Pharma, Sanofi Aventis, Jannsen Cilag outside of the scope of this study. SB declares having received nonfinancial support from Kyowa Kirin and Recordati. MBag declares consulting fees from Kyowa Kirin, Takeda, Recordati. HB declares consultant fees from Kyowa Kirin. EH declares consultant fees outside the scope of this study from Bristol-Myers Squibb, Takeda, Sanofi, Jannsen Cilag, Blueprint Medicines, AbbVie and nonfinancial support from Kyowa Kirin, MSD, UCB Pharma, Novartis, Almirall, Pierre Fabre. The other authors declare that they have no conflict of interest., (© 2024 The Authors.)

Primary cutaneous lymphomas (PCLs) are a heterogeneous group of lymphoproliferative disorders caused by the accumulation of neoplastic T or B lymphocytes in the skin. Sézary syndrome (SS) is an aggressive and rare form of cutaneous T cell lymphoma (CTCL) characterized by an erythroderma and the presence of atypical cerebriform T cells named Sézary cells in skin and blood. Most of the available treatments for SS are not curative, which means there is an urgent need for the development of novel efficient therapies. Recently, targeting cancer metabolism has emerged as a promising strategy for cancer therapy. This is due to the accumulating evidence that metabolic reprogramming highly contributes to tumor progression. Genes play a pivotal role in regulating metabolic processes, and alterations in these genes can disrupt the delicate balance of metabolic pathways, potentially contributing to cancer development. In this review, we discuss the importance of targeting energy metabolism in tumors and the currently available data on the metabolism of Sézary cells, paving the way for potential new therapeutic approaches aiming to improve clinical outcomes for patients suffering from SS.

Background: Cemiplimab (Libtayo ® ), a human monoclonal immunoglobulin G4 antibody to the programmed cell death-1 receptor, is approved for the treatment of patients with advanced cutaneous squamous cell carcinoma (CSCC), who are not candidates for curative surgery or curative radiation, using an every-3-weeks (Q3W) dosing interval. Pharmacokinetic modeling indicated that C trough of extended intravenous dosing of 600 mg every 4 weeks (Q4W) would be comparable to the approved intravenous dosage of 350 mg Q3W. We examined the efficacy, pharmacokinetics, and safety of cemiplimab dosed Q4W., Methods: In this open-label, phase II trial (ClinicalTrials.gov identifier NCT02760498), the cohort of patients ≥18 years old with advanced CSCC received cemiplimab 600 mg intravenously Q4W for up to 48 weeks. Tumor measurements were recorded every 8 weeks. The primary endpoint was objective response rate by independent central review., Results: Sixty-three patients with advanced CSCC were treated with cemiplimab. The median duration of follow-up was 22.4 months (range: 1.0-39.8). An objective response was observed in 39 patients (62%; 95% CI: 48.8% to 73.9%), with 22% of patients (n = 14) achieving complete response and 40% (n = 25) achieving partial response. The most common treatment-emergent adverse events were diarrhea, pruritus, and fatigue., Conclusions: Extended dosing of cemiplimab 600 mg intravenously Q4W exhibited substantial antitumor activity, rapid and durable responses, and an acceptable safety profile in patients with advanced CSCC. These results confirm that cemiplimab is a highly active therapy for advanced CSCC. Additional data would help ascertain the benefit-risk profile for the 600 mg intravenous dosing regimen compared with the approved regimen., Competing Interests: Competing interests: DR reports institutional research grants and funding from Bristol-Myers Squibb, GlaxoSmithKline, Kura Oncology, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc, ALX Oncology, Decibel Therapeutics and Roche; and uncompensated scientific committee and advisory board membership from GlaxoSmithKline, Merck Sharp & Dohme, Regeneron Pharmaceuticals, Inc and Sanofi. BGMH reports consulting or advisory roles at AstraZeneca, Bristol-Myers Squibb, Eisai, Merck Sharp & Dohme, Pfizer and Roche; and institutional research funding from Amgen. NB-S declares no conflict of interest. DS reports institutional patients’ fees from Regeneron Pharmaceuticals, Inc; advisory board, speaker honoraria and patients’ fees from Bristol-Myers Squibb, EMD Serono, Merck Sharp & Dohme, Novarti and Pierre Fabre; steering committee honoraria from 4SC, Bristol-Myers Squibb, InflaRx, Merck Sharp & Dohme, Nektar and Novartis; advisory board fees from Daiichi Sanyo, OncoSec Medical, Pfizer and Replimune; advisory board and patients’ fees from Philogen and Sun Pharma; and research funding to their institution from Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme and Novartis. SB reports an advisory board role or speaker bureau for Sanofi, Ipsen, Lilly, Bristol-Myers Squibb and Merck Sharp & Dohme Australia; and virtual meeting sponsorship from Bristol-Myers Squibb and Merck Sharp & Dohme Australia. ST reports speaker honoraria and advisory board fees from AbbVie, Bristol-Myers Squibb, Novartis, Pierre Fabre and Sun Pharma. FM reports travel support, speaker’s fees or advisor’s honoraria from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Roche and Sanofi; and research funding from Novartis and Roche. TE reports consulting or advisory roles at Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Roche and Sanofi Genzyme; speaker’s bureau roles at Merck Sharp & Dohme and Roche; and research funding from Bristol-Myers Squibb and Novartis. VCE reports advisory board honoraria from AstraZeneca, GlaxoSmithKline, Merck Sharp & Dohme and Pharmamar; and speaker honoraria from AstraZeneca and Merck Sharp & Dohme. BS reports advisory board membership for Bristol-Myers Squibb Australia and Merck Sharp & Dohme. MBB reports serving as a speaker without honoraria for Sanofi. SD reports advisory board honoraria and travel expenses from Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, PFO Global and Sun Pharma. BD reports consultancy for Sanofi. MRM reports honoraria and travel expenses from Genentech, Eli Lilly, Novartis, Regeneron Pharmaceuticals, Inc, Sanofi and Sun Pharma; and institutional research funding from Genentech, Eli Lilly, Novartis and Regeneron Pharmaceuticals, Inc. AH reports institutional grants, speaker’s honoraria and consultancy fees from Amgen, Bristol-Myers Squibb, Merck Sharp & Dohme, Novartis, Pierre Fabre, Provectus and Roche; institutional grants and consultancy fees from EMD Serono, Philogen and Regeneron Pharmaceuticals, Inc; and consultancy fees from OncoSec Medical. CDS reports steering committee membership for Castle Biosciences; steering committee membership and consultancy for Regeneron Pharmaceuticals, Inc; consultancy for Sanofi; research funding from Castle Biosciences, Genentech, Merck, Novartis and Regeneron Pharmaceuticals, Inc; and serving as a chair for the National Comprehensive Cancer Network. AML reports uncompensated advisory board participation from Merck Sharp & Dohme and Bristol-Myers Squibb with travel and accommodation expenses; and uncompensated consultancy for Eisai. S-YY, APaccaly, APapachristos, J-HN, EO, FS, JB and IL are employees of and shareholders in Regeneron Pharmaceuticals, Inc. MGF is an employee of, has patents pending with, and is a shareholder of Regeneron Pharmaceuticals, Inc. AG reports personal fees and nonfinancial support (advisory board and travel support) from Bristol-Myers Squibb and Sun Pharma; personal fees (advisory board) from Eisai, Merck KGaA and Pfizer; non-financial support (travel) from Astellas; and clinical trial unit support from PPD Australia., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: Another course of immune checkpoint inhibitors (ICIs) is often considered in patients with cancer progression and previous immune-related adverse events, including inflammatory arthritis (ICI-IA), but there are limited data regarding safety of ICI rechallenge in this setting. We aimed to assess the rate and clinical features associated with ICI-IA flare/recurrence on ICI rechallenge., Methods: We conducted a multicentre observational study including cancer patients with ICI-IA who started a second course of ICI more than 3 months after ICI discontinuation in four French university hospitals. Primary outcome was the frequency of ICI flare/recurrence after ICI rechallenge., Results: Twenty-three patients were included. At the time of ICI rechallenge, 18 patients reported no symptoms of ICI-IA (78%) and 5 had grade 1 (22%), 11 patients (48%) were not receiving any ICI-IA treatment, 11 (48%) were still on prednisone, 2 (9%) were on conventional synthetic disease-modifying antirheumatic drugs and 1 (4%) on anti-IL-6. ICI-IA flare/recurrence occurred in 12 patients (52%) with a median time of 1 month after ICI rechallenge. ICI-IA phenotype, disease activity and ICI-IA treatment at the time of ICI rechallenge did not differ according to ICI-IA flare/recurrence status., Conclusion: In this first observational study of ICI-IA patients rechallenged with ICI, about half of the patients experienced ICI-IA flare/recurrence with a similar phenotype but occurring earlier than the initial ICI-IA, warranting close monitoring during the first month of retreatment. Risk of flare did not differ according to baseline immunosuppressive treatment at the time of rechallenge., Competing Interests: Competing interests: AL and TB: No conflict of interest. GM: Research support: Abbvie, BMS, Gilead, Lilly, MSD, Novartis, Roche Chugai, Sanofi; consulting fees: Abbvie, UCB, BMS, Lilly, Gilead, Novartis, Janssen; education: Abbvie, BMS, Gilead, Lilly, Novartis, Roche Chugai. AT: Consulting fees: Galapagos; speaker: Brystol-Myers Squibb; support for attending congress: Sanofi, Abbvie. SB: Co conflict of interest. SP, CD: Congress fees and investigator in clinical trials: BMS and MSD. EG: Congress fees and investigator for BMS and MSD. AP-L and MB-B: No conflict of interest. MZ: Grants from AVAD and grants from FRM. RV: Consulting fees and speaker fees: Roche; registration reimbursement: Pfizer and AstraZeneka; speaker and registration reimbursement: BMS and MSD. AD: Consulting or Advisory Role: Merck, MSD, BMS, Merus; travel, accommodations, expenses: BMS, Merck. MG-G: Consulting or Advisory Role: Astra Zeneca, Merck, Pfizer, MSD, BMS, Roche; travel, accommodations, expenses: MSD, Janssen. BS: no conflict of interest. FL: Congress fees, consulting fees, and sub investigator in trials: Astra Zeneca, BMS, MSD, Roche, Pfizer. ML, CR and M-ET: No conflict of interest. TS: Clinical research: AbbVie, Abivax, Biogen, Pfizer, Lilly, MSD, Novartis, Sandoz; advisory Boards: AbbVie, BMS, Lilly, Novartis, Pfizer, Sanofi; education: AbbVie, Biogen, BMS, Galapagos, Lilly, Janssen, Novartis, Nordic Pharma, Pfizer, Viatris; help for research: Pfizer, Lilly, Abbvie, Biogen. MK: No conflict of interest., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)