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

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.

Tebentafusp in Patients with Metastatic Uveal Melanoma: A Real-Life Retrospective Multicenter Study

“…In one patient, tebentafusp induced a life-threatening tumor lysis syndrome—a rare side effect that was also observed in one patient among the 245 patients treated within the Phase 3 trial. In contrast to cytokine-related adverse events, which mainly occur during the first tebentafusp infusions, ICI can induce a broad spectrum of so-called immune-related adverse events that can even be elicited after the cessation of ICI treatment and are mainly managed with corticosteroids [ 23 ].…”

Immunologic Profiling of Immune-Related Cutaneous Adverse Events with Checkpoint Inhibitors Reveals Polarized Actionable Pathways

“…These ircAEs are the first to present, some as early as 4 to 8 weeks since the initiation of therapy ( 10 , 12 ); are usually persistent, with variable time to resolution ( 10 ); and may negatively impact the quality of life (QoL; refs. 13 , 14 ) and therapeutic dose intensity ( 10 , 15 – 18 ). To date, standard clinical practice and society guidelines recommend the use of histamine H1 receptor blockers, and topical/oral corticosteroids for ircAEs, which have limited efficacy for grade 2 to 3 ircAEs ( 15 ), are associated with additional toxicities, may impact the antitumor effects of CPIs ( 19 ), and are unsustainable for long-term use ( 20 ).…”

“…13 , 14 ) and therapeutic dose intensity ( 10 , 15 – 18 ). To date, standard clinical practice and society guidelines recommend the use of histamine H1 receptor blockers, and topical/oral corticosteroids for ircAEs, which have limited efficacy for grade 2 to 3 ircAEs ( 15 ), are associated with additional toxicities, may impact the antitumor effects of CPIs ( 19 ), and are unsustainable for long-term use ( 20 ). Whereas various clinical presentations and histologic findings have been reported retrospectively, a prospective study has not been systematically conducted to assess outcomes ( 14 ) and define biomarkers ( 21 ) reflective of ircAE pathogenic mechanisms.…”