Timeline of Adverse Events during Immune Checkpoint Inhibitors for Advanced Melanoma and Their Impacts on Survival

SIMPLE SUMMARY: A cohort of 153 melanoma patients treated with immune checkpoint inhibitors as first line therapy were studied, to specifically describe the timelines of all adverse events by the target organ, demonstrating a different profile of appearance over time. Interestingly, the survival benefit of presenting immune-related adverse events was demonstrated only for dermatological events, but a multivariate analysis found that this benefit is no longer significant after adjusting for the duration of therapy and the baseline stage of disease. In our opinion, the apparent good response marker of adverse events needs to be analyzed, taking into account the time in therapy and other prognostic markers, such as disease burden. ABSTRACT: Immune-related adverse events (irAEs) are frequent and could be associated with improved response to immune checkpoint inhibitors (ICIs). A prospective cohort of advanced melanoma patients receiving ICI as first-line therapy was retrospectively reviewed (January 2011–February 2019). A total of 116 of 153 patients presented with at least one irAE (75.8%). The most frequent irAEs were dermatological (derm irAEs, 50%), asthenia (38%), and gastrointestinal (29%). Most irAEs appeared within the first 90 days, while 11.2% appeared after discontinuation of the therapy. Mild grade 1–2 derm irAEs tended to appear within the first 2 months of therapy with a median time of 65.5 days (IQR 26-139.25), while grade 3–4 derm irAEs appeared later (median 114 days; IQR 69-218) and could be detected at any time during therapy. Only derm irAE occurrence was related to improved survival (HR 6.46). Patients presenting derm irAEs showed better 5-year overall survival compared to those with no derm irAEs (53.1% versus 24.9%; p < 0.001). However, the difference was not significant when adjusting for the duration of therapy. In conclusion: the timeline of immune-related-AEs differs according to the organ involved. The (apparent) improved survival of patients who present derm AEs during immunotherapy could be partially explained by longer times under treatment.