Adverse Effects of Immune Checkpoint Inhibitors (Programmed Death-1 Inhibitors and Cytotoxic T-Lymphocyte-Associated Protein-4 Inhibitors): Results of a Retrospective Study

Abstract

In recent years the use of immunomodulating therapy to treat various cancers has been on the rise. Three checkpoint inhibitors have been approved by the Food and Drug Administration (ipilimumab, pembrolizumab and nivolumab). The use of these drugs comes with serious adverse events related to excessive immune activation, collectively known as immune-related adverse events (irAEs). We conducted a system-based review of 139 case reports/case series that have described these adverse events between January 2016 and April 2018, found in the PubMed database. There was a broad spectrum of presentations, doses and checkpoint inhibitors used. The most common check point inhibitor observed in our literature review was nivolumab. The most common adverse effects encountered were colitis (14/139), hepatitis (11/139), adrenocorticotropic hormone insufficiency (12/139), hypothyroidism (7/139), type 1 diabetes (22/139), acute kidney injury (16/139) and myocarditis (10/139). The treatment most commonly consisted of cessation of the immune checkpoint inhibitor, initiation of steroids and supportive therapy. This approach provided a complete resolution in a majority of cases; however, there were many that developed long-term adverse events with deaths reported in a few cases. The endocrine system was the mostly commonly affected with the development of type 1 diabetes mellitus or diabetic ketoacidosis being the most frequently reported adverse events. While immunomodulating therapy is a significant advance in the management of various malignancies, it is capable of serious adverse effects. Because the majority of the cases developed pancreatic dysfunction within five cycles of therapy, in addition to the evaluation of other systems, pancreatic function should be closely monitored to minimize adverse impact on patients.

Severe Cerebellar Syndrome Linked With Durvalumab

“…In the case of ICI-associated neurological complications, therapeutic strategy most commonly involves cessation of the ICI, with the initiation of IV or oral steroids combined with supportive therapies. This approach provided a complete resolution in a majority of cases; however, many patients developed irreversible adverse events including deaths reported in a few cases [8]. In steroid-refractory cases, immunomodulatory treatments with PLEX or IVIg may be effective [9].…”

Development of a Functional Assessment of Chronic Illness Therapy item library and primary symptom list for the assessment of patient-reported adverse events associated with immune checkpoint modulators

“…Our literature review yielded 25 articles documenting irAE incidence, management guidelines, toxicity profiles, and associated symptomatology [4,9,[11][12][13][14][15][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56][57] . From these, we identified 75 possible inflammatory reactions/immune conditions across 11 organ systems, ranging from very common to rare.…”

Cardiovascular Vulnerability to COVID-19 in Cancer Survivors

“…Importantly, trastuzumab has been shown to augment anthracycline-induced cardiotoxicity [62]. Novel immune check point inhibitors have also been associated with increased risk of myocarditis [63]. Although less frequent at low doses, cyclophosphamide-induced symptomatic cardiotoxicity occurs in 5-28% of patients treated with high doses [64,65].…”