Cancer and treatment specific incidence rates of immune-related adverse events induced by immune checkpoint inhibitors: a systematic review

Abstract

Background: Immune-related adverse events (irAE) induced by immune checkpoint inhibitors (ICI) are a treatment-limiting barrier. There are few large-scale studies that estimate irAE prevalence. This paper presents a systematic review that reports the prevalence of irAE by cancer type and ICI.

Methods: A systematic review was undertaken in MEDLINE OVID, EMBASE and Web of Science databases from 2017-2021. A total of 293 studies were identified for analysis and, of these, event rate was calculated for 272 studies, which involved 58,291 patients with irAE among 305,879 total patients on ICI. Event rate was calculated by irAE and ICI type.

Results: Mean event rate for general irAE occurrence across any grade was 40.0% (37.3-42.7%) and high grade was 19.7% (15.8-23.7%). Mean event rates for six specific types of irAE are reported. Mean event rate for ICI monotherapy was 30.5% (28.1-32.9%), 45.7% (29.6-61.7%) for ICI combination therapy, and 30.0% (25.3-34.6%) for both ICI monotherapy and combination therapy.

Conclusion: This systematic review characterises irAE prevalence across current research that examines irAE risk factors across cancers and ICI. The findings confirms that irAE occurrence is very common in the real-world setting, both high grade and irAE across any grade.

Fig. 1

PRIMSA flowchart.

Fig. 2. Box and whisker distribution of general irAE occurrence for any grade and high grade among included studies.

n = 175 studies. Any grade: minimum 3.5%; first quartile 29.3%; median 40.0%; third quartile 49.4%; maximum 84.0%; mean 40.0%; interquartile range 20.1%. High grade: minimum 1.7%; first quartile 9.6%; median 16.9%; third quartile 25.8%; maximum 56.0%; mean 19.7%; interquartile range 16.2%.

Fig. 3. Box and whisker distribution of specific irAE occurrence for any grade and high grade among included studies.

n = 118 studies. Cardiac: minimum 0.8%; first quartile 2.2%; median 5.9%; third quartile 37.6%; maximum 52.3%; mean 18.0%; interquartile range 35.4%. Endocrine: minimum 1.5%; first quartile 12.4%; median 22.8%; third quartile 33.5%; maximum 65.6%; mean 23.9%; interquartile range 21.0%. Gastrointestinal: minimum 1.3%; first quartile 5.7%; median 12.5%; third quartile 33.3%; maximum 52.5%; mean 19.4%; interquartile range 27.6%. Pulmonary: minimum 2.8%; first quartile 11.7%; median 15.0%; third quartile 24.7%; maximum 45.4%; mean 18.9%; interquartile range 13.0%. Renal: minimum 1.4%; first quartile 4.5%; median 14.9%; third quartile 17.3%; maximum 50.0%; mean 15.5%; interquartile range 12.8%. Skin: minimum 16.7%; first quartile 18.2%; median 25.1%; third quartile 40%; maximum 47.7%; mean 28.7%; interquartile range 21.8%. Note: Due to low number of studies, event rates are not presented for musculoskeletal and neurologic irAE.

Fig. 4. Box and whisker distribution of specific irAE occurrence for different ICI treatment types.

n = 269 studies. Monotherapy: minimum 0.1%; first quartile 17.1%; median 29.7%; third quartile 43.5%; maximum 84.0%; mean 30.5%; interquartile range 26.4%. Combination: minimum 12.8%; first quartile 24.9%; median 48.0%; third quartile 66.3%; maximum 71.7%; mean 45.7%; interquartile range 41.4%. Combination & monotherapy: minimum 0.4%; first quartile 9.8%; median 32.6%; third quartile 46.3%; maximum 84.0%; mean 30.0%; interquartile range 36.5%.