Correlation between immune-related adverse events and prognosis in patients with various cancers treated with anti PD-1 antibody.

Abstract

Background: Immune checkpoint inhibitors (ICIs) targeting programmed cell death protein 1 (PD-1) are used for the treatment of various cancer types. However, immune-related adverse events (irAEs) occur in patients treated with ICIs. Several small-scale studies have reported the onset of irAEs and therapeutic effects of ICIs. Here we report a large-scale retrospective study covering a wide range of cancers. We evaluated irAEs and the therapeutic effects of ICIs and determined whether irAEs could be predicted.Methods: This study included patients treated with the anti-PD-1 antibodies nivolumab or pembrolizumab at Fujita Health University Hospital between December 2015 and March 2019. We retrospectively reviewed the electronic medical records for age, cancer type, pre-treatment blood test data, presence or absence of irAE onset, type and severity of irAEs, outcome of irAE treatment, response rate, progression-free survival and overall survival.Results: Two hundred-eighty patients received ICIs. The overall incidence of irAEs was 41.1% (115 patients), and the incidence of severe irAEs of grade 3 and higher was 2.8% (eight patients). The most common irAEs were skin disorders, thyroid disorders and interstitial pneumonia. Patients with irAEs were significantly older than those without irAEs (69.7 versus 66.0 years, P=0.02). The objective response rate (ORR) in patients with irAEs was 30.4%, which was significantly higher than in patients without irAEs (12.7%; P<0.01). Both the median overall and progression-free survival were significantly longer in patients with irAEs. Based on the blood test data obtained before ICI therapy, hypothyroidism, thyroid-stimulating hormone levels and thyroglobulin antibody levels were associated with the onset of irAEs. In many patients with irAEs of Common Terminology Criteria for Adverse Events Grade 3 or higher, re-administration of ICIs was difficult, and their outcomes were poor. In contrast, many patients with irAEs of a lower grade were able to resume ICI therapy.Conclusion: Although the onset of irAEs was difficult to be predicted based on pre-treatment tests. It appeared that the continuation of ICI therapy, along with early detection and adequate control of irAEs, might contribute to the improved prognosis of patients.

Correlation Between Immune-related Adverse Events and Therapeutic Effects of Nivolumab in Patients With Malignant Pleural Mesothelioma

“…Matsuoka H, et al recently analyzed a cohort with various types of cancer including MPM, and showed that ORR, OS and PFS were signi cantly better in the patients with irAEs than in those without irAEs. 19 Although this cohort included only four MPM patients in total 260 cases, none of them developed irAEs, therefore, it was still unclear whether there is a correlation between irAEs and therapeutic effect in patients with MPM. In this study, we examined the eight patients with MPM, and showed the PFS in the patients with irAEs was signi cantly longer than their counterpart.…”

Lymphatic-Preserving Treatment Sequencing with Immune Checkpoint Inhibition Unleashes cDC1-Dependent Antitumor Immunity in HNSCC

“…Recent reports from the clinical literature have demonstrated a positive correlation between the onset of immune-related adverse events (irAEs) and the tumor response to ICI (73)(74)(75), suggesting that effective IO therapy should be reflected and manifest proximal to the TIME. In line with this observation, we found that lymphatic-sparing treatment sequencing activated both regional and peripheral host antitumor immunity.…”

Lymphatic-Preserving Treatment Sequencing with Immune Checkpoint Inhibition Unleashes cDC1-Dependent Antitumor Immunity in HNSCC

“…Recent reports from the clinical literature have demonstrated a positive correlation between the onset of immune-related adverse events (irAEs) and the tumor response to ICI [77][78][79] , suggesting that effective IO therapy should be reflected and manifest proximal to the TIME. In line with this observation, we found that lymphatic-sparing treatment sequencing activated both regional and peripheral host antitumor immunity.…”