Abstract
Simple SummaryIn this study, we investigated the impact of immune-related adverse events (irAEs) on the survival of advanced melanoma patients treated with immune-checkpoint inhibitors, as well as the effect of corticosteroids and other immune-modulators on clinical outcome. We summarized the kinetics, onset, and outcome of immune-related adverse events (irAEs) in both adjuvant and non-adjuvant settings and we correlated their onset with disease outcome.Immune checkpoint inhibitors (ICIs) can induce immune-related adverse events (irAEs), which may result in treatment discontinuation. We sought to describe the onset, frequency, and kinetics of irAEs in melanoma patients in a real-life setting and to further investigate the prognostic role of irAEs in treatment outcomes. In this retrospective single-center cohort study, we included 249 melanoma patients. Onset, grade, and resolution of irAEs and their treatment were analyzed. A total of 191 (74.6%) patients in the non-adjuvant and 65 (25.3%) in the adjuvant treatment setting were identified. In the non-adjuvant setting, 29 patients (59.2%) with anti-CTLA4, 43 (58.1%) with anti-PD1, and 54 (79.4%) with anti-PD1/anti-CTLA4 experienced some grade of irAE and these had an improved outcome. In the adjuvant setting, the frequency of irAEs was 84.6% in anti-CTLA4 and 63.5% in anti-PD1, but no correlation with disease relapse was observed. Patients with underlying autoimmune conditions have a risk of disease exacerbation. Immunomodulatory agents had no impact on treatment efficacy. IrAEs are correlated with increased treatment efficacy in the non-adjuvant setting. Application of steroids and immunomodulatory agents, such as anti-TNF-alpha or anti-IL6, did not affect ICI efficacy. These data support irAEs as possible prognostic markers for ICI treatment.
Highlights
Immune checkpoint inhibitors (ICIs) such as anti-PD1 and anti-CTLA4 antibodies have revolutionized the therapeutic landscape of metastatic melanoma and are approved as first-line therapies in the advanced as well as the adjuvant setting [1,2,3,4]
In patients treated with combined anti-CTLA4/anti-PD1, immune-related adverse events (irAEs) of any grade can be observed with a frequency of up to 90% and may lead to treatment discontinuation in up to 50% of patients [8]
We investigated the prognostic impact of irAEs on survival and the effect of steroids and other immunomodulators on clinical outcome
Summary
Immune checkpoint inhibitors (ICIs) such as anti-PD1 (programmed cell death 1) and anti-CTLA4 (cytotoxic T lymphocyte antigen 4) antibodies have revolutionized the therapeutic landscape of metastatic melanoma and are approved as first-line therapies in the advanced as well as the adjuvant setting [1,2,3,4]. In patients treated with combined anti-CTLA4/anti-PD1 (ipilimumab and nivolumab), irAEs of any grade can be observed with a frequency of up to 90% and may lead to treatment discontinuation in up to 50% of patients [8]. In cases of steroid-refractory irAEs like colitis, pneumonitis, arthritis, and hepatitis, other immunomodulatory treatments such as blocking antibodies against tumor necrosis factor alpha (TNF-α) or interleukin 6 (IL6) were shown to be effective [5,9,10,11]. It remains unclear whether these interventions have a negative impact on the antitumor immune response. High-dose steroids for long durations during anti-PD1 therapy may be associated with poorer survival outcomes [13]
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