Phase I/Ib study of concurrent combination of intravenous (IV) and intrathecal (IT) nivolumab and relatlimab for metastatic melanoma (MM) patients (pts) with leptomeningeal disease (LMD)

Background: Malignancies increase blood coagulability, and immune checkpoint inhibitors (ICI) are an additional thrombosis risk factor.Data on thrombosis in metastatic melanoma patients is limited, with the cumulative incidence of venous thrombosis after 6 months of ICI therapy estimated at 5-8% and 10% after 12 months.The study highlights venous thrombosis as an ICI complication.Methods: The data were collected through a retrospective analysis from our database and statistically processed.Results: From 2019 to 2024, 208 melanoma patients were treated at the Department of Dermatology and Venereology of the Military Medical Academy, including 140 men and 68 women.Monoclonal anti-PD-1 therapy, either alone or with CTLA-4 inhibitors, was the first-line treatment for 172 patients.Among those treated with ICIs, 4.06% developed thromboembolic events (TE), consistent with existing literature, with a higher incidence of 85.7% in women.The average age was 60.5 years.Of the 7 patients with thrombosis, 5 were on pembrolizumab or nivolumab monotherapy, 1 on nivolumab/ipilimumab combination, and 1 on nivolumab/trametinib therapy.Four developed pulmonary embolism (PE), one had concurrent PE and deep vein thrombosis (DVT), and three had isolated DVT.The maximum Cochran score for these patients was 1. Four patients were at stage IV, and 28.5% had initially metastatic changes in the central nervous system.One patient developed TE during progression from stage IIIC to stage IV.The average time to TE onset was 5.08 months, ranging from 3 days to one year.None had a prior history of thrombosis.Upon TE diagnosis, all had elevated d-dimer levels.Four had involvement of three or more organs, including distant lymph nodes.Anemia was present in 57.1%, elevated LDH in 42.85%, and elevated protein S-100 in 57.14%.Given that malignancy cannot be excluded, further studies are needed, particularly on patients not receiving ICI and those treated with BRAF and MEK inhibitors, for more precise insights.Conclusions: Thrombosis is not so rare complication of immunooncological therapy, with higher risk in the first six months.