Investigating the Impact of Immune-Related Adverse Events, Glucocorticoid Use and Immunotherapy Interruption on Long-Term Survival Outcomes

Abstract

It remains unclear whether immune-related adverse events (irAEs) and glucocorticoid use could impact long-term outcomes in patients treated for solid tumors with immune checkpoint inhibitors (ICI). All patients treated with a single-agent ICI for any advanced cancer were included in this retrospective unicentric study. The objectives were to assess the impact of grade ≥3 irAEs, glucocorticoid use and the interruption of immunotherapy on progression-free survival (PFS) and overall survival (OS). In this 828-patient cohort, the first occurrence of grade ≥3 irAEs had no significant impact on PFS or OS. Glucocorticoid administration for the irAEs was associated with a significantly shorter PFS (adjusted HR 3.0; p = 0.00040) and a trend toward shorter OS. ICI interruption was associated with a significantly shorter PFS (adjusted HR 3.5; p < 0.00043) and shorter OS (HR 4.5; p = 0.0027). Glucocorticoid administration and ICI interruption were correlated. In our population of patients treated with single agent ICI, grade ≥3 irAEs did not impact long-term outcomes. However, the need for glucocorticoids and the interruption of immunotherapy resulted in poorer long-term outcomes. The impact of grade ≥3 irAEs reported in other studies might then be explained by the management of the irAEs.

Immunosuppression for immune-related adverse events during checkpoint inhibition: an intricate balance

“…Several studies making comparisons within the group of patients with irAEs, demonstrate a detrimental effect of high dose corticosteroids on ICI efficacy, while no unfavourable effect was observed in other studies (Fig. 3 and Supplementary table 3 ) 13 , 41 , 46 , 47 , 56 – 66 . Most of the latter studies reported on small groups or low-dose corticosteroid use during ICI irrespective of indication, or included multiple types of cancer or ICI which have different survival and toxicity profiles and are often unequally distributed among groups.…”

The effects of glucocorticoids and immunosuppressants on cancer outcomes in checkpoint inhibitor therapy

“…Some data suggests that early use of glucocorticoids (within 60 days of ICIs) may be associated with worse cancer outcomes, but further studies are needed to validate this finding. Recent data also suggests that this may also be due in part due to interruption or discontinuation of ICIs while patients have irAEs ( 8 ). Finally, glucocorticoids are used at varying dosages and durations depending on the type and severity of the irAE being treated.…”

Do corticosteroids affect immunotherapy efficacy in malignancy? – A systematic review

“…Secondly, mixed reports are found regarding the effects of corticosteroids on survival when used for the treatment of irAE. While Mouri et al reported a negative effect from use of corticosteroids to treat irAE on both overall survival (OS) and progression free survival (PFS) (23) , Bruyère et al reported a negative effect on PFS, but not on OS (24) and multiple other studies reported that systemic corticosteroids for treatment of irAE do not reduce the survival effect of ICI (25)(26)(27)(28)(29)(30)(31)(32) . Thirdly, several studies showed that ICI are effective in autoimmune conditions, even when combined with systemic corticosteroids (33)(34)(35) .…”