The relationship between immune-related adverse events during ipilimumab monotherapy and survival outcomes among melanoma patients: A systematic review

Abstract

Background Ipilimumab disinhibits immune system activity which results in the elimination of malignant cells. An unintended consequence of ipilimumab therapy is off-target immune-related adverse events (irAEs). It has therefore been proposed that the incidence of irAEs is a manifestation of treatment effectiveness. The objective of this systematic review is to examine the relationship between irAEs and survivability among melanoma patients administered ipilimumab monotherapy. Methods A comprehensive search was conducted across several databases which yielded a total of 2381 studies. Clinical trials and prospective studies administering ipilimumab monotherapy to melanoma patients were included. Furthermore, there was no restriction placed on publication date. After screening, five studies were included for data extraction. The primary outcome of median overall survival (OS) and the secondary outcome of OS hazard ratio were extracted from the included studies. Results Based on qualitative analysis of the included studies, there seemed to be an association between the occurrence of non-lethal irAEs and improved survival outcomes among melanoma patients administered ipilimumab monotherapy. With that being said, the poorer survivability among patients who experienced high-grade irAEs may be the result of subsequent treatment discontinuation. Potential confounders such as corticosteroid use should be accounted for. Finally, landmark analyses may be conducted to account for immortal time bias. Conclusions The findings from this systematic review provide evidence suggesting that the incidence of irAEs is a marker of an improved anti-tumor response.