Multiple immune-related adverse events and anti-tumor efficacy: real-world data on various solid tumors

Abstract

Background Immune checkpoint inhibitors have been approved for various types of cancer; however, they cause a broad spectrum of immune-related adverse events (irAEs). The association between the development of irAEs and the clinical benefit remains uncertain. We aimed to evaluate the association of irAEs and the treatment efficacy in the real-world practice. Methods We conducted a retrospective study on patients with recurrent or metastatic non-small cell lung cancer, melanoma, renal cell carcinoma, or gastric cancer who received anti-PD-1/PD-L1 antibodies (nivolumab, pembrolizumab, or atezolizumab) at the Keio University Hospital between September 2014 and January 2019. We recorded treatment-related AEs from medical records and graded them using the Common Terminology Criteria for Adverse Events version 4. We performed an overall survival (OS) analysis using a Cox proportional hazards model. Results Among 212 patients eligible for this study, 108 experienced irAEs and 42 developed multiple irAEs. OS in patients with multiple irAEs was significantly longer than that in patients with single irAE (42.3 months vs. 18.8 months; hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.25–0.93; P = 0.03). Moreover, OS from the development of a second irAE in those with multiple irAEs was longer than that from the development of the first irAE in patients with single irAEs (median OS, 26.9 months vs. 17.7 months, respectively; HR, 0.59; 95% CI, 0.30–1.14; P = 0.11). Conclusions Our single-center retrospective study revealed a remarkable tendency associating the development of multiple irAEs with favorable prognoses.

A Durable Response after the Discontinuation of Nivolumab in an Advanced Gastric Cancer Patient

“…Recent studies have shown that the development of irAE was associated with a clinical benefit in several cancers, including AGC (22)(23)(24)(25)(26)(27)(28). In NSCLC patients, in whom irAEs developed within 2 weeks from the start of nivolumab treatment (25), in whom more than two irAEs were reported (26), or in whom either endocrine irAEs or skin irAEs (28), a more pronounced benefit was observed.…”

Analysis of Risk Factors for Immune-Related Adverse Events in Various Solid Tumors Using Real-World Data

“…Indeed, the association between irAEs and patient outcomes (e.g., treatment-related death, treatment discontinuation and prognosis) is of great importance for further understanding the clinicopathological features of irAEs. In a previously published research article, the authors reported on the association between the incidence of irAEs and favorable prognosis in clinical practice and revealed that the development of multiple irAEs is associated with a better prognosis [28]. In the present study, the authors mainly focused on the cumulative incidence and risk factors for irAEs and the appropriate method for analyzing the incidence of irAEs.…”

“…Although not statistically different, patients with Type I hypersensitivity reactions had a tendency to develop severe irAEs, which might lead to discontinuation of ICI treatment. Interestingly, several studies have reported an association between the development of irAEs and a favorable prognosis in various malignancies [28,40]. Indeed, the association between irAEs and patient outcomes (e.g., treatment-related death, treatment discontinuation and prognosis) is of great importance for further understanding the clinicopathological features of irAEs.…”

“…A conventional multivariate analysis is inadequate for evaluating the risk factors for irAEs; instead, a cumulative incidence analysis is appropriate. In previous work, the authors reported that the development of multiple irAEs might be associated with a favorable prognosis [28]. Here the authors specifically focused on the risk factors for irAEs and conducted a retrospective study using updated data from the previous work.…”

Prognostic Impact of Immune-Related Adverse Events on Patients with and Without Cardiovascular Disease: A Retrospective Review

“…Since 2015, various studies have reported that irAEs are associated with a longer prognosis regardless of the treatment regimen [5,6]. Shimozaki et al reported that the development of multiple irAEs was associated with longer survivals than a single irAE [19]. Conversely, Naqash et al reported the negative impact of irAE-related treatment discontinuation on survival [20].…”