Importance: Few data are available on patients with leptomeningeal disease (LM) from melanoma treated with new systemic therapies. Objective: To gain a better understanding of patients, disease characteristics, and therapeutic interventions in melanoma patients with LM in the era of new systemic treatment. Design: Clinical characteristics, treatments, and survival of melanoma patients diagnosed with LM, isolated or associated with brain metastases, were collected. The Cox regression model assessed the influence of patient and melanoma characteristics on survival. Setting: Monocentric, retrospective, real-life cohort of patients with LM from melanoma. Participants: All patients followed up at Saint-Louis University Hospital and diagnosed with LM between December 2013 and February 2020 were included. For each patient identified, a central review by dermato-oncologist and neuro-oncologist experts was performed to confirm the diagnosis of LM. Exposure: Impact of new systemic therapies and radiotherapy. Results: Among the 452 advanced melanoma patients followed at St Louis Hospital between 2013 and 2020, 41 patients with LM from melanoma were identified. Among them, 29 patients with a diagnosis of LM “confirmed” or “probable” after central neuro-oncologists reviewing were included. Nineteen patients had known melanoma brain metastases at LM diagnosis. Among the 27 patients treated with systemic therapy, 17 patients were treated with immunotherapy, 5 patients received targeted therapy, 1 was treated with chemotherapy, and 4 patients were treated with anti-PD-1 in combination with BRAF inhibitor. The median overall survival (OS) from LM diagnosis was 5.1 months. Median OS was 7.1 months for the 9 patients receiving systemic therapy combined with radiotherapy, and 3.2 months for the 20 patients not receiving combined radiotherapy. Elevated serum lactate dehydrogenase (LDH) (HR 1.44, 95% CI 1.09–1.90, p < 0.01) and presence of neurological symptoms at LM diagnosis (HR 2.96, 95% CI 1.25–6.99, p = 0.01) were associated with poor survival. At the time of data analysis, five patients were still alive with a median follow-up of 47.4 months and had persistent complete response. Conclusion: Targeted therapy and immunotherapy are promising new treatment options in LM from melanoma that can increase overall survival, and may induce long lasting remission in some patients.

Background: Immune checkpoint inhibitors (ICI) are currently the first-line treatment for patients with metastatic melanoma. We investigated the value of positron emission tomography (PET) response criteria to assess the therapeutic response to first-line ICI in this clinical context and explore the potential contribution of total tumor metabolic volume (TMTV) analysis. Methods: We conducted a retrospective study in patients treated with first-line ICI for advanced or metastatic melanoma, with 18F-FDG PET/CT performed at baseline and 3 months after starting treatment. Patients’ metabolic response was classified according to PERCIST5 and imPERCIST 5 criteria. TMTV was recorded for each examination. Results: Twenty-nine patients were included. The median overall survival (OS) was 51.2 months (IQR 13.6—not reached), and the OS rate at 2 years was 58.6%. Patients classified as responders (complete and partial response) had a 90.9% 2-year OS rate versus 38.9% for non-responders (stable disease and progressive disease) (p = 0.03), for PERCIST5 and imPERCIST 5 criteria. The median change in metabolic volume was 9.8% (IQR −59–+140%). No significant correlation between OS and changes in TMTV was found. Conclusion: The evaluation of response to immunotherapy using metabolic imaging with PERCIST5 and imPERCIST5 was significantly associated with OS in patients with advanced or metastatic melanoma.

Nine drugs have been marketed for 10 years for the treatment of advanced melanoma (AM). With half of patients reaching a second line, the optimal sequence of treatments remains unclear. To inform policy-makers about their efficiency, we performed a cost-effectiveness analysis of sequential strategies in clinical practice in France, for BRAF-mutated and wild-type patients. A multistate model was developed to describe treatment sequences, associated costs, and health outcomes over 10 years. Sequences, clinical outcomes, utility scores, and economic data were extracted from the prospective Melbase cohort, collecting individual data in 1518 patients since 2013, from their AM diagnosis until their death. To adjust the differences in patients’ characteristics among sequences, weighting by inverse probability was used. In the BRAF-mutated population, the MONO-targeted therapies (TT)-anti-PD1 sequence was the less expensive, whereas the anti-PD1-BI-TT sequence had an incremental cost-effectiveness ratio (ICER) of 180,441 EUR/QALY. Regarding the BRAF wild-type population, the three sequences constituted the cost-effective frontier, with ICERs ranging from 116 to 806,000 EUR/QALY. For BRAF-mutated patients, the sequence anti-PD1-BI-TT appeared to be the most efficient one in BRAF-mutated AM patients until 2018. Regarding the BRAF wild-type population until 2018, the sequence starting with IPI+NIVO appeared inefficient compared to anti-PD1, considering the extra cost for the QALY gained.