The following is a summary of “Corticosteroids and other immunosuppressants for immune-related adverse events and checkpoint inhibitor effectiveness in melanoma,” published in the June 2024 issue of Oncology by Verheijden et al.
Recent research has highlighted a potential link between the use of immunosuppressants for managing immune-related adverse events (irAEs) and reduced survival rates in patients undergoing immune checkpoint inhibitor therapy. However, the specific impact of corticosteroids versus second-line immunosuppressants remains unclear. This study, the largest of its kind to date, aimed to evaluate the relationship between the type and dosage of immunosuppressants and survival outcomes in patients with melanoma experiencing irAEs.
Researchers included patients with advanced melanoma from 18 hospitals worldwide, all of whom received immunosuppressants for irAEs induced by first-line anti-PD-1 therapy, with or without anti-CTLA-4. Using multivariable Cox proportional hazards regression, the study group assessed the associations between cumulative and peak doses of corticosteroids and the use of second-line immunosuppressants with survival from the start of immunosuppressive treatment.
Among the 606 patients in the study, 404 experienced irAEs related to anti-PD-1 combined with anti-CTLA-4, while 202 had irAEs related solely to anti-PD-1. Of these, 425 patients (70%) were treated exclusively with corticosteroids, and 181 (30%) required additional second-line immunosuppressants. Median progression-free survival (PFS) and overall survival (OS) from the onset of immunosuppression were 4.5 months (95% CI 3.4-8.1) and 31 months (95% CI 15-not reached), respectively, for patients receiving second-line immunosuppressants. In contrast, patients treated only with corticosteroids had a median PFS of 11 months (95% CI 9.4-14) and an OS of 55 months (95% CI 41-not reached).
A high peak dose of corticosteroids was significantly associated with poorer PFS (HRadj 1.14; 95% CI 1.01-1.29) and OS (HRadj 1.29; 95% CI 1.12-1.49 for 80 mg vs. 40 mg). In contrast, cumulative corticosteroid dose did not significantly impact survival outcomes. Additionally, the use of second-line immunosuppressants was linked to worse PFS (HRadj 1.32; 95% CI 1.02-1.72) and OS (HRadj 1.34; 95% CI 0.99-1.82) compared to corticosteroid monotherapy.
In conclusion, both high-peak doses of corticosteroids and the use of second-line immunosuppressants are associated with reduced survival in patients with melanoma treated for irAEs. While immunosuppression is essential for managing severe irAEs, clinicians must carefully balance the potential negative impact on survival with the risks of inadequate treatment. This study underscores the importance of optimizing immunosuppressive strategies to enhance patient outcomes.
Source: sciencedirect.com/science/article/pii/S0959804924008281
