Steroid-Refractory Immune-Related Adverse Events Induced by Checkpoint Inhibitors

Cancers (Basel). 2023 Apr 28;15(9):2538. doi: 10.3390/cancers15092538.

Abstract

The occurrence, second-line management and outcome of sr/sd-irAEs was investigated in patients with skin cancer. All skin cancer patients treated with immune checkpoint inhibitors (ICIs) between 2013 and 2021 at a tertiary care center were analyzed retrospectively. Adverse events were coded by CTCAE version 5.0. The course and frequency of irAEs were summarized using descriptive statistics. A total of 406 patients were included in the study. In 44.6% (n = 181) of patients, 229 irAEs were documented. Out of those, 146 irAEs (63.8%) were treated with systemic steroids. Sr-irAEs and sd-irAEs (n = 25) were detected in 10.9% of all irAEs, and in 6.2% of ICI-treated patients. In this cohort, infliximab (48%) and mycophenolate mofetil (28%) were most often administered as second-line immunosuppressants. The type of irAE was the most important factor associated with the choice of second-line immunosuppression. The Sd/sr-irAEs resolved in 60% of cases, had permanent sequelae in 28% of cases, and required third-line therapy in 12%. None of the irAEs were fatal. Although these side effects manifest in only 6.2% of patients under ICI therapy, they impose difficult therapy decisions, especially since there are few data to determine the optimal second-line immunosuppression.

Keywords: second-line immunosuppression; skin cancer; steroid-dependent immune-related adverse events; steroid-refractory immune-related adverse events.

Grants and funding

The study was supported by the the SERIO registry which is supported by the Stiftung Immunonkologie (FA 18-005) and the Förderverein des Tumorzentrums der Universität Erlangen-Nürnberg. This work was also supported by the German Federal Ministry of Education and Research (BMBF) as part of the project emed:MelAutim (01ZX1905E to LH).