Background: In 2020, melanoma exhibited the 5th highest incidence rate of all cancers in the US. While metastatic melanoma constitutes only 4% of new melanoma cases, the 5-year survival rate of metastatic melanoma is 27% [1]. Immune Checkpoint Inhibitors (ICIs) were the first drugs to significantly improve the 5-year survival of late-stage melanoma patients; these include ipilimumab (Yervoy®), nivolumab (Opvido®), and pembrolizumab (Keytruda®), all of which are monoclonal antibodies that combat the immunosuppressive tumor microenvironment [2]. Recently, Agarwal et al. demonstrated that 38% of late-stage melanoma patients were prescribed glucocorticoids to alleviate immune-related adverse events (irAEs) secondary to ICI use [3]; however, these same patients were also shown to have reduced overall survival [4]. Therefore, it is important to evaluate whether the concurrent use of immunosuppressive glucocorticoid with ICIs diminishes ICI efficacy.
Methods: This is a retrospective study conducted on late-stage melanoma patients receiving ICI therapy at Dartmouth-Hitchcock Medical Center (DHMC) between 1/1/2015 and 4/1/2020. All patients who met these inclusion criteria were identified and the following data was entered into RedCap: date of diagnosis, stage of cancer at diagnosis, treatment, preexisting comorbidities requiring the use of steroids, onset and type of irAE, days from start of ICI to irAEs, days from start of ICI to start of steroids, initial steroid dose, highest steroid dose, total duration of steroid use, duration of treatment response, next line after disease progression on ICI, overall survival, baseline Neutrophil-Lymphocytic Ratio (NLR), baseline eosinophil count, NLR at 2 and 4 weeks of steroids, eosinophil count at 2 and 4 weeks of steroids. Any data that could not be found excluded the patient from statistical analyses, which are still being conducted.
Results: This retrospective study at DHMC aims to evaluate the treatment efficacy of ICIs among late-stage (stage 3 and 4) melanoma patients receiving corticosteroids. Our preliminary data shows that a majority of late-stage melanoma patients at DHMC who received ICIs as part of their treatment course were concurrently on corticosteroids, either for preexisting comorbidities (18%) or irAEs secondary to ICIs (62%). Additionally, almost 70% of late-stage melanoma patients on ICIs experience irAEs, and a majority of those patients subsequently required corticosteroids to manage their irAEs. Notably, almost half of these patients were initiated on high-dose (i.e. immunosuppressive) corticosteroids. While the results of this study continue to be analyzed, we hypothesize that a high-dose (>20 mg prednisone or equivalent) or prolonged course (>21 days) of corticosteroids will diminish ICI efficacy, as determined by these patients’ NLR and overall survival.
Conclusions: The data to date suggests that it will be important to understand the potentially detrimental impact of corticosteroids on ICI treatment efficacy and overall survival in our late-stage melanoma patients, as this will allow us to become more judicious in prescribing corticosteroids to this patient population.
