Cardiovascular disease mortality risk among patients with metastatic melanoma before and after the approval of immunotherapy in the United States: a Surveillance, Epidemiology, and End Results database-based study.

Background: To date, the population-based cardiovascular mortality (CVM) of metastatic melanoma has not been studied in the era of immune checkpoint inhibitors (ICIs). This study aims to assess the risk of CVM in patients with metastatic melanoma in the pre-ICI (2000-2010) and post-ICI (2011-2020) eras.

Methods: This study using the Surveillance, Epidemiology, and End Results database from 2000 to 2020 of patients with metastatic melanoma. Standardized mortality ratios (SMRs) and absolute excess risks were calculated for CVM before and after the introduction of ICIs. To evaluate the cumulative mortality (CM) rate for all causes of death, cumulative hazard curves were constructed. Competing risk models were established to determine the independent predictors for CVM.

Results: This study included 8857 patients, 3803 in the pre-ICI era and 5054 in the post-ICI era. A total of 281 deaths were attributed to cardiovascular diseases. The overall SMRs of CVM were 27% higher (SMR = 1.27, 95% CI 1.06-1.50) in the pre-ICI era and 56% higher (SMR = 1.56, 95% CI 1.31-1.83) in the post-ICI era than the general population, reaching 2.17 during the early stage of latency (0-5 months). Additionally, independent risk factors for CVM included age, primary site, and brain metastases in the post-ICI era.

Conclusions: Metastatic melanoma patients exhibited an elevated CVM risk after the approval of ICIs, peaking in early latency period and older population. Timely monitoring and effective interventions for cardiovascular diseases may be warranted in patients with metastatic melanoma, especially in the immunotherapy era.