Colite ulcérée sévère lors d’un traitement par ipilimumab sans récidive après cure d’infliximab et relai secondaire par pembrolizumab

National audienc

Personalized follow-up of circulating DNA in resected stage III/IV melanoma: PERCIMEL multicentric prospective study protocol

International audienceBackground: With more than 15,000 new cases /year in France and 2,000 deaths, cutaneous melanoma represents approximately 4% of incidental cancers and 1.2% of cancer related deaths. In locally advanced (stage III) or resectable metastatic (stage IV) melanomas, medical adjuvant treatment is proposed and recent advances had shown the benefit of anti-PD1/PDL1 and anti-CTLA4 immunotherapy as well as anti-BRAF and anti-MEK targeted therapy in BRAF V600 mutated tumors. However, the recurence rate at one year is approximately 30% and justify extensive research of predictive biomarkers. If in metastatic disease, the follow-up of circulating tumor DNA (ctDNA) has been demonstrated, its interest in adjuvant setting remains to be precised, especially because of a lower detection rate. Further, the definition of a molecular response could prove useful to personalized treatment. Methods: PERCIMEL is an open prospective multicentric study executed through collaboration of the Institut de Cancérologie de Lorraine (non-profit comprehensive cancer center) and 6 French university and community hospitals. A total of 165 patients with resected stage III and IV melanoma, eligible to adjuvant imunotherapy or anti-BRAF/MEK kinase inhibitors will be included. The primary endpoint is the presence of ctDNA, 2 to 3 weeks after surgery, defined as mutated ctDNA copy number calculated as the allelic fraction of a clonal mutation relative to total ctDNA. Secondary endpoints are recurrence-free survival, distant metastasis-free survival and specific survival. We will follow ctDNA along treatment, quantitatively through ctDNA mutated copy number variation, qualitatively through the presence of cfDNA and its clonal evolution. Relative and absolute variations of ctDNA during follow-up will be also analyzed. PERCIMEL study aims at provide scientific evidence that ctDNA quantitative and qualitative variations can be used to predict the recurrence of patients with melanoma treated with adjuvant immunotherapy or kinase inhibitors, thus defining the notion of molecular recurrence

Clinical and Sociodemographic Characteristics Associated With Thick Melanomas: A Population-Based, Case-Case Study in France.

International audienceOBJECTIVE To identify clinical and sociodemographic factors associated with very thick melanoma (VTM) (Breslow thickness, ≥3 mm) in France. DESIGN Retrospective, population-based, case-case study using a survey of cancer registries and questionnaires to practitioners. SETTING Five regions covering 19.2% of the French territory and 8.2 million inhabitants. CASES Cases included all incident melanomas with a Breslow thickness of 3 mm or greater (ie, VTM), diagnosed between January 1 and December 31, 2008, in residents of the study area (Alsace, Bourgogne, Champagne-Ardenne, Franche-Comté, and Lorraine, France), and a randomly selected sample of melanomas thinner than 3 mm. MAIN OUTCOME MEASURES Circumstances of diagnosis, clinical and pathological characteristics of melanomas, and sociodemographic characteristics of patients (age, sex, residence, home and family life conditions, educational level, and smoking habits). RESULTS Among 898 melanomas, 149 (16.6%) were VTMs. Very thick melanomas were more often diagnosed in a general-practice setting than thinner melanomas. The rate of immediate clinical recognition by dermatologists was lower for VTMs than for thinner melanomas. In a multivariate logistic regression analysis, factors associated with VTM were the nodular and acrolentiginous types; the head and neck and lower limb locations; older age; male sex; and being single, separated, divorced, or widowed. When only factors related to patients were taken into account, older age, male sex, and living alone were independent risk factors for VTM. The most significant risk was observed for patients living alone. CONCLUSIONS Intrinsic factors related to the tumor and sociodemographic characteristics of patients contribute to the occurrence of VTM. These factors should be better targeted in future secondary prevention programs

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

International audienc

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

International audienceBackground: 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

Variations in management of stage I to stage III cutaneous melanoma: a population-based study of clinical practices in France.

International audienc

Risk of irAEs in patients with autoimmune diseases treated by immune checkpoint inhibitors for stage III or IV melanoma: results from a matched case–control study

International audienceObjective To quantify the risk of immune-related adverse events (irAEs) in patients with pre-existing autoimmune disease (pAID) treated by immune checkpoint inhibitors (ICIs) for stage III or IV melanoma. Methods Case–control study performed on a French multicentric prospective cohort of patients with melanoma, matched for irAE risk factors and oncological staging. Risk of irAE was assessed by logistic regression. Results 110 patients with pAID were included and matched with 330 controls, from March 2013 to October 2020. Over a median follow-up period of 7.2 months for cases and 6.9 months for controls, the ORs of developing all-grade and grade ≥3 irAEs among cases compared with controls were 1.91 (95% CI (1.56 to 2.27)) and 1.44 (95% CI (1.08 to 1.82)), respectively. Patients with pAID had an increased risk of multiple irAEs (OR 1.46, 95% CI (1.15 to 2.67)) and a shorter time to irAE onset. In contrast, there were no difference in irAE-related mortality nor in the rate of treatment discontinuation, and a landmark analysis revealed a better survival at 24 months among cases (p=0.02). Thirty per cent of cases experienced a pAID flare during follow-up, and baseline immunosuppression did not prevent irAE occurrence. Last, we report associations between the pAID clinical subsets and organ-specific irAEs. Conclusion In our study, patients with pAID were at greater risk of all-grade, severe and multiple irAEs, yet had a better 24-month survival than controls. Thus, patients with pAID should be eligible for ICI therapy but benefit from a close monitoring for irAE occurrence, especially during the first months of therapy

The role of circumstances of diagnosis and access to dermatological care in early diagnosis of cutaneous melanoma: a population-based study in France.

International audienc