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

Area of Science:

• Oncology
• Immunology
• Dermatology

Background:

• Immune checkpoint inhibitors (ICIs) are crucial in skin cancer treatment.
• Immune-related adverse events (irAEs) are common, but steroid-resistant/dependent irAEs (sr/sd-irAEs) pose management challenges.
• Optimal second-line immunosuppression for sr/sd-irAEs remains poorly defined.

Purpose of the Study:

• To investigate the occurrence, management, and outcomes of sr/sd-irAEs in skin cancer patients treated with ICIs.
• To identify factors influencing second-line immunosuppression choices.
• To evaluate the efficacy and sequelae of different treatment strategies.

Main Methods:

• Retrospective analysis of 406 skin cancer patients treated with ICIs from 2013-2021.
• Adverse events classified using CTCAE version 5.0.
• Descriptive statistics used to summarize irAE frequency, course, and treatment outcomes.

Main Results:

• 229 irAEs occurred in 44.6% of patients; 63.8% were treated with systemic steroids.
• Sr/sd-irAEs occurred in 6.2% of ICI-treated patients (10.9% of all irAEs).
• Infliximab (48%) and mycophenolate mofetil (28%) were most common second-line agents; irAE type influenced choice.
• Sr/sd-irAEs resolved in 60%, had permanent sequelae in 28%, and required third-line therapy in 12%.

Conclusions:

• Sr/sd-irAEs represent a significant subset of irAEs in ICI-treated skin cancer patients, necessitating careful management.
• The choice of second-line immunosuppression is influenced by irAE type, with infliximab and mycophenolate mofetil frequently used.
• While many sr/sd-irAEs resolve, a notable proportion lead to permanent sequelae or require further treatment, highlighting the need for further research into optimal therapeutic strategies.