Trends in melanoma mortality among U.S. adults aged ≥55 before and after the introduction of immunotherapy: A CDC WONDER Joinpoint-style analysis.

e21579 Background: Immune checkpoint inhibitors (ICIs) have transformed the treatment of advanced melanoma and produced durable survival benefits in clinical trials. However, the population-level impact of immunotherapy on melanoma mortality remains incompletely characterized. We examined national melanoma mortality trends before and after the introduction of ICIs to assess whether therapeutic advances translated into accelerated reductions in mortality at the population level. Methods: We conducted a retrospective population-based analysis using the CDC WONDER Underlying Cause of Death database from 1999–2020. Deaths due to malignant melanoma (ICD-10 C43) among adults aged ≥55 years were identified. Annual age-adjusted mortality rates standardized to the 2000 U.S. population were analyzed using Joinpoint-style segmented log-linear regression to identify changes in temporal trends and estimate annual percent changes (APC) before and after the identified breakpoint. Results: From 1999 to 2020, melanoma mortality among adults aged ≥55 years demonstrated a significant inflection point in 2012. Prior to 2012, age-adjusted mortality increased by an average of 1.1% per year. After 2012, mortality declined significantly, with an accelerated decrease of 2.2% per year (p<0.001 for change in slope). The post-2012 decline was sustained through 2020, reaching the lowest mortality rates observed during the study period. The timing of the inflection closely corresponded with the early dissemination of immune checkpoint inhibitors in routine clinical practice. Conclusions: In this nationwide analysis of adults aged ≥55 years, melanoma mortality demonstrated a modest decline prior to the availability of immune checkpoint inhibitors, followed by a significantly accelerated and sustained reduction thereafter. This temporal pattern is consistent with substantial population-level benefits associated with the introduction of modern immunotherapy. Continued surveillance and efforts to expand equitable access to early detection and advanced systemic therapies may be critical to further reducing melanoma mortality and minimizing disparities across demographic groups. Joinpoint-style analysis of melanoma mortality trends among U.S. adults aged ≥55 years, 1999–2020. Time period Years Annual Percent Change (APC) P value Interpretation Pre-immunotherapy 1999-2011 +1.1 per year < 0.001 Mortality increased prior to immunotherapy Immunotherapy era 2012-2020 -2.2% per year < 0.001 Accelerated decline in mortality after immunotherapy Breakpoint year: 2012. Outcome: Age-adjusted melanoma mortality per 100,000 (2000 U.S. standard population). Method: Joinpoint-style segmented log-linear regression.