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International audience; The prognosis of advanced melanoma has been greatly improved by new therapeutic agents and clinicians rely on dynamic signals to drive their therapeutic choices. Although the kinetics of metastatic disease seem to be correlated with survival, progression of the localized disease is not predictable.Objective: To assess whether progression of metastatic disease is associated with the time to the first distant recurrence of melanoma.Design, Setting, and Participants: This study was conducted from March 1, 2013, to September 1, 2017, among 638 adults with unresectable stage III or IV melanoma within the French multicentric prospective cohort MelBase. Patients treated with first-line immunotherapies, targeted therapies, or chemotherapy were included. Patients with unknown primary or de novo metastatic melanoma were not included. Data were analyzed from March 1, 2013, to December 1, 2017.Main Outcomes and Measures: The date of primary excision and time to first distant recurrence, progression-free survival, and overall survival were collected. Cox proportional hazards regression models were planned to assess the association between time to first distant recurrence and progression-free survival or overall survival, which was evaluated in terms of hazard ratio (HR). Time to recurrence was analyzed both as a continuous and categorical variable (24 months).Results: A total of 638 patients (272 women and 366 men; median age, 64 years [interquartile range, 52-73 years]) were included in the study. The median time from primary excision to first distant recurrence was 25 months (interquartile range, 12-55 months). There was no evidence of association of the time to recurrence with progression-free survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.99-1.01) or after categorization (12-24 months: HR, 0.75; 95% CI, 0.56-1.02; >24 months: HR, 0.62; 95% CI; 0.47-1.01). There was no evidence of association of the time to recurrence with overall survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.98-1.02) or after categorization (12-24 months: HR, 0.76; 95% CI, 0.54-1.07; >24 months: HR, 0.61; 95% CI, 0.54-1.03). Those results remained nonsignificant after stratification by treatment.Conclusions and Relevance: In the MelBase cohort, time to recurrence of metastatic melanoma appears not to be associated with progression-free survival or overall survival.

9550 Background: Since the development of immune checkpoint inhibitors (ICI) for advanced melanoma, a small group of patients with an excellent and durable response has emerged. Complete response (CR) is achievable in about 10-20% of the patients and seem to have an excellent prognosis. However, 10 to 15% of them might relapse eventually. Our main objective was to determine factors associated with relapse after a CR to ICI in advanced melanoma. The second objective was to describe relapse modalities and tumor response to subsequent treatments. Methods: We performed a single-center, retrospective study, in 141 patients with a CR to ICI for advanced melanoma, treated at Gustave Roussy (France) from January 2010 to June 2020. CR was confirmed on two consecutive CT-scanner or PET-CT at least 3 months apart. Characteristics of the patients at diagnosis, during and after treatment were compared in both groups: CR with relapse and CR without relapse. The LASSO analysis, a statistical analysis using lambda penalization coefficient for prognostic studies, was performed regarding the many statistical variables analysed. Results: At data analysis, immunotherapy was interrupted in 94.3% of the patients and the median follow-up was 3.5 years since immunotherapy discontinuation. Eventually, 18 of 141 patients (12.8%) had relapsed and 126 (87.2%) had not. The statistical analysis identified three factors associated with melanoma recurrence: prior lines of therapy, the type of melanoma and the mutation status. Indeed, relapse risk was higher in patients with wild type melanoma (as opposed to BRAF or NRAS mutant melanoma), with a mucosal, acral or unknown primitive melanoma and who received prior lines of treatment. Other factors such as demographical characteristics, tumor burden, metastasis localization, type or grade of toxicity, pseudo progression, type of ICI, treatment duration, use of a complementary local treatment and pursuit/discontinuation of immunotherapy were not statistically associated with the duration of the complete response. In case of melanoma recurrence, reintroduction of immunotherapy provided tumor response in half of our patients: 13 of the 18 relapsing patients received immunotherapy after melanoma recurrence; allowing 3 CR, 2 partial responses and 1 stable disease. One third of the relapsing patients eventually died of disease progression. Conclusions: This study confirmed the excellent prognosis of CR to ICI in advanced melanoma, even after treatment discontinuation and identified 3 baseline factors associated with a risk of relapse: absence of BRAF or NRAS mutation, primary of acral, mucosal or unknown origin, and previous lines of therapy. Rechallenge with ICI was effective in 50% of the patients.

9538 Background: In the past decade, the prognosis of advanced melanoma has been greatly improved by new therapeutic agents such as immune and targeted therapies, which are now being evaluated as adjuvant therapies. Although the kinetic of metastatic disease is correlated to patient survival, the unfolding of the dormant disease remains hardly predictable and data from the literature on the topic is controversial (Karakousis, Francken). We hypothesized that the course of the advanced disease could be predicted from time to distant recurrence. Methods: Melbase is a French multicentric cohort dedicated to the prospective follow-up of adults with unresectable stage III or IV melanoma. Date of primary excision, time to recurrence, progression free survival (PFS) and overall survival (OS) of 298 patients treated in first line by immune therapies (IT, n = 148), targeted therapies (TT, n = 68) or within clinical trials (n = 73) were collected on September 5th, 2016. Patients with unknown primary or de novo metastatic melanoma were not included. Time to distant recurrence was analyzed as a continuous variable and as a categorical variable ( < 12 months; 12 to 24 months; ≥ 24 months). Results: Patients’ characteristics at baseline are: mean age 62 years, PS 0-1 84%, elevated LDH 32%, BRAF mutated 39%, brain metastases 18%. Time to recurrence studied as a continuous variable was not correlated to PFS (HR = 0.96; 95%CI: 0.85-1.07) or OS (HR = 0.89; 95%CI: 0.77-1.03). These results remained insignificant after stratification upon treatment or even when time to recurrence was analyzed as a categorized variable. Conclusions: Our data showed no correlation between the time from primary to distant recurrence and PFS or OS in patients treated with TT or IT. Therefore, kinetics of advanced disease cannot be predicted by the history of dormant disease. Dormancy and metastasis proliferation are thus probably driven by different molecular and cellular mechanisms.