The Relative Risk and Incidence of Immune Checkpoint Inhibitors Related Pneumonitis in Patients With Advanced Cancer: A Meta-Analysis

Abstract

Background: Recently, immune checkpoint inhibitors (ICIs) have been proved one of the most promising anti-cancer therapy, series clinical trials have confirmed their efficacy. But they are also associated with distinctive set of toxic effects, which are recognized as immune-related adverse events. Among those immune-related adverse events, pneumonitis is rare, but it is often clinically serious and potentially life-threatening. Although many clinical trial results of PD-1/PD-L1 inhibitors had been reported incidence of pneumonitis, the knowledge based on the individual cohort data from each clinical trial is limited. So we conducted a meta-analysis of trials of PD-1/PD-L1 inhibitors in patients with advanced cancer and compared relative risk and incidence among different tumor types and therapeutic regimens. Such an analysis may provide important knowledge of this rare but clinically significant and potentially serious immune-related adverse event.Methods: Electronic databases were used to search eligible literatures, include randomized controlled trials (RCTs) comparing immune checkpoint inhibitors vs. standard therapies. All-grade (1–4) or high-grade (3–4) pneumonitis events were extracted. The summary relative risk, summary incidence, and 95% confidence intervals were calculated.Results: The incidence of all-grade and high-grade pneumonitis in non-small cell lung cancer (NSCLC) was significantly higher compared with other tumor types, such as Melanoma, urothelial carcinoma (UC), head and neck squamous cell carcinoma (HNSCC) (3.1% vs. 2.0%; p = 0.02, 1.4% vs. 0.6%; p = 0.03). The risk of all-grade pneumonitis was obtained from all patients in both experimental arm and control arm. Treatment with immune checkpoint inhibitors targeting PD-1/PD-L1 did significantly increase the risk of all-grade and high-grade pneumonitis compared with controls (fixed effects, RR: 4.70; 95% CI: 2.81–7.85; p < 0.00001, RR: 3.33; 95% CI: 1.68–6.59; p = 0.0006).Conclusion: The incidence of immune checkpoint inhibitors related pneumonitis was higher in NSCLC than other tumor types. Patients treated with immune checkpoint inhibitor in experiment arms are more likely to experience any grade pneumonitis than control arms. These findings suggest that clinician need to draw more attention on this rare but serious adverse event.

Pulmonary complications of immune checkpoint inhibitors in patients with nonsmall cell lung cancer

“…https://doi.org/10.1183/16000617.0058-2019 study on NSCLC only [59], the ICI-P incidence was 4.8% (3.8-5.7%) for all grades and 2.0% (2-2.9%) for grades 3-5. In a third study [58], the frequency of ICI-P is 2.6% (1.7-3.8%) for all grades and all tumours.…”

“…Clarifications provided by systematic reviews and meta-analyses on irAEs In December 2018, several systematic reviews conducted on irAEs [21,22,[50][51][52][53][54] and, more specifically, on respiratory adverse events including ICI-P [55][56][57][58][59][60], involved nine to 48 randomised controlled prospective trials including 3500-15 000 patients. These studies involved patients with either any cancer type [22, 50-55, 57, 58, 60] or only NSCLC [21,56,59], treated either with any ICI [22, 50-52, 55, 57, 60] or only anti-PD-1/PD-L1 inhibitors [21,53,54,56,58,59]. These studies present significant methodological differences, with epidemiological data on ICI-P summarised in table 1.…”

Organ-Specific Immune-Related Adverse Events Associated With Immune Checkpoint Inhibitor Monotherapy Versus Combination Therapy in Cancer: A Meta-Analysis of Randomized Controlled Trials

“…Currently, although several meta-analysis have evaluated the efficacy and safety of ICIs (Wang et al, 2017;Barroso-Sousa et al, 2018;Ma et al, 2018;Wang et al, 2018;You et al, 2018), most studies included chemotherapy as the control group for the analysis, and few studies specifically assessed the safety of ICIs. A published meta-analysis by Wang et al in 2018 reported fatal toxic effects associated with ICIs.…”

Vildagliptin‐induced ground‐glass nodules mimicking lung metastases in a cancer patient receiving Lactobacillus probiotic supplementation

“…The association between gut microbiota and the lung immune system may be critical in the treatment outcome of lung cancer . Moreover, various drugs are prone to cause interstitial pneumonia (IP) in lung cancer patients, at least in part through immunological mechanisms . However, little is known about the effects of probiotics on drug‐induced IP in cancer patients.…”