Immune-Related Adverse Events (irAEs): Implications for Immune Checkpoint Inhibitor Therapy
Year: 2020
Type: article
Abstract: I mmune checkpoint inhibitors (ICIs) have revolutionized the treatment of ad- vanced malignancies, including non-small cell lung cancer (NSCLC).Although these agents have improved clinical outcomes in NSCLC, they have also led to unique toxicities, termed immune-related adverse events (irAEs).1-3 irAEs are the result of nonspecific immune activation and can affect any organ system, although they most commonly occur in the skin, liver, gastrointestinal tract, and endocrine systems.4 In this issue of JNCCN, Kichenadasse et al 5 evaluate the incidence of irAEs occurring in a group of 1,548 patients with NSCLC treated with atezolizumab monotherapy on 4 clinical trials.[6][7][8][9] The authors used individual patient data from these trials to explore the incidence and timing of single-organ and multiorgan irAEs, the latter defined as either concurrent or sequential depending on whether irAEs arose within 7 days of one another.The primary objectives were to evaluate the incidence, grade, and time course of irAEs, in addition to assessing correlation with clinical outcomes (overall and progression-free survival).Kichenadasse et al 5 also conducted an in-depth evaluation of multiorgan irAEs, which is of particular interest because information regarding these types of AEs is currently sparse.Among the 4 atezolizumab NSCLC trials evaluated, multiorgan irAEs occurred in 5.4% of patients.To date, very little information is available on the frequency, significance, and management of multiorgan irAEs.Studies that have reported frequency of multiorgan irAEs have cited incidences from 5% to 43% across multiple tumor types, encompassing both single-agent and multiagent ICI treatment modalities.[10][11][12][13][14][15][16][17][18] Interestingly, previously published reports have shown that the development of irAEs correlates with patient response rate and survival.19,20 In a 2019 study, Cortellini et al 12 found that overall survival, progression-free survival, and objective response rates were higher among patients with NSCLC who experienced irAEs during treatment with anti-PD-1 agents; however, no significant difference in these endpoints was observed when comparing single-site versus multiple-site irAEs.In contrast, Kichenadasse et al 5 found that multiorgan involvement was associated with better survival outcomes than were observed with single-organ involvement.The question of whether multiorgan irAEs are associated with improved survival in patients with NSCLC is important because this information could potentially help guide decisions about whether to continue treatment with ICIs in the face of treatment-related toxicity.If multiorgan irAEs are truly associated with improved survival outcomes, clinicians and patients may choose to forge ahead with ICI treatment despite multiorgan toxicity, when possible.To assist with this critical decision, effective tools are needed to predict which patients are most likely to experience serious and/or fatal toxicities.Currently, however, no refined tools are available to predict development of ICI-induced irAEs, and surveillance for occurrence generally relies on traditional laboratory markers.21 At the very least, developing predictive tools would allow for more relevant discussion between clinicians and patients during ICI therapy.Given the dramatic improvement in See page 1191 for related article.
Institutions: University of California, Los Angeles, UCLA Health
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
OpenAlex ID: W3083367621