Real-World Adherence to Toxicity Management Guidelines for Immune-Related Adverse Events

Abstract

Immune checkpoint inhibitors (ICIs) affect immunologic homeostasis, leading to immune-related adverse events (irAEs). Early irAE detection and management can prevent significant morbidity and mortality. A retrospective chart review was performed to characterize irAEs associated with nivolumab, ipilimumab, and nivolumab plus ipilimumab in adult medical oncology patients in Nova Scotia Health-Central Zone from 2013–2020, and to describe adherence to toxicity management guidelines. Diarrhea/colitis, hepatitis, pneumonitis, nephrotoxicity, and cardiotoxicity were studied. Of 129 charts reviewed, 67 patients (51.9%) experienced at least one irAE for a total of 98 irAEs and a 1.5% fatality rate. Of these irAEs, 33.7% led to an emergency room visit. Patients were admitted to hospital and steroids were used in 24.5% and 35.7% of cases, respectively. In 17.3% of irAEs, ICIs were permanently discontinued. In 20.4% of irAEs, ICIs were held, and patients were monitored; while in 18.4%, ICIs were held until the irAE was Grade 0–1 (and until steroids were tapered). Almost 47% of irAEs were managed according to guidelines (14.3% were not), and 38.8% had no documented management. Patients receiving immunotherapy frequently experience irAEs with half of irAEs having documented management adhering to guidelines. As immunotherapy indications expand, it is important to ensure irAEs are documented and managed appropriately.

Raising awareness of immune-related side effects in oncological patients under palliative care: a report of two cases

“…Adding up, patients in PC often present with sarcopenia, which is another risk factor for irAEs (17). Since palliative treatment regimens are increasingly implemented nowadays, palliative patients are at high risk of developing late onset high grade irAEs more than six months after starting ICI treatment and need continuous follow-up care (8,20,21). Involving PC early on leads to better symptom control (22), timely end of life discussions and a reduction in readmissions to hospital which ameliorates the patients' overall quality of life (16)(17)(18)23).…”

“…Inpatient admission is often required in this setting. If an irAE is suspected or cannot be excluded, first-line therapy is the timely administration of corticosteroids (e.g., methylprednisolone 1-2 mg/kg/body weight) (20,29).…”

“…Recently, additive immunomodulators in the case of corticosteroid resistant side effects became of interest in the treatment of irAEs. These include CTLA-4 agonists such as abatacept, calcineurin inhibitors like tacrolimus or the IgG1 antibody infliximab (4,10,20,37). In late onset irAEs more than a year after initiation of ICI therapy up to a quarter of patients are in need of additional immunomodulators (8).…”

Nivolumab Hypersensitivity Reactions a Myth or Reality in Solid Tumors—A Systematic Review of the Literature

“…Severe dirAEs (grade 3 and grade 4) require the administration of high-dose systemic corticosteroid treatment, intense supportive care management, and wound management. In some cases, it is a must to administer tumor necrosis factor alpha (TNF-α) inhibitors (Infliximab or Etanercept), Mycophenolate mofetil, Cyclosporin, and even plasmapheresis [ 34 , 36 ] These reactions require a definitive interruption of immunotherapy [ 38 , 39 , 40 ].…”

Early Effects of Nivolumab and Ipilimumab Combined Immunotherapy in the Treatment of Metastatic Melanoma in Poland: A Multicenter Experience

“…Prompt AEs management and, if possible, immunotherapy continuation are important since they might improve the patient’s prognosis as we demonstrated in the case report from our clinic [ 43 ]. For example, a study from Nova Scotia demonstrated that only half of immunotherapy-related AEs are managed according to guidelines and about 17% of discontinued patients were withdrawn too early for this reason [ 44 ]. The authors postulated that it may be caused by the aversion of some physicians to administer high-dose steroids, as it potentially may inhibit the immunotherapy effect.…”