Emerging concerns of infectious diseases in lung cancer patients receiving immune checkpoint inhibitor therapy

Abstract

Backgrounds: Cancer immunotherapy using immune checkpoint inhibitors has received a remarkable amount of attention in patients with non-small cell lung cancer (NSCLC). The unique adverse effects known as immune-related adverse events (irAEs) associated with immune checkpoint inhibitors are not known however, and neither is the incidence of infectious disease among patients receiving immune checkpoint inhibitors. The aims of this study were to investigate the incidence of infections during nivolumab treatment, and the risk factors associated with infections.

Methods: We retrospectively reviewed NSCLC patients who received nivolumab in two teaching hospitals (National Hospital Organization Kyoto Medical Center and Kyoto University Hospital, Kyoto, Japan) between December 2015 and June 2017. We counted any infectious diseases occurring at any time after the initiation of nivolumab until 3 months after its discontinuation. In the current study, "infectious disease" was defined as any infection requiring the administration of any antimicrobial agent.

Results: Of a total of 167 NSCLC patients reviewed, 32 (19.2%) experienced infectious diseases. Of the 33 infections in 32 patients, 25 were bacterial, 2 were fungal, and 6 were viral. Twenty-seven of the patients with infections used corticosteroids during their treatment course. There was no statistically significant difference in the use of immunosuppressive agents between patients with and without infections. A history of diabetes mellitus was significantly associated with infection (odds ratio 3.61, 95% confidence interval 1.14-11.4, p = 0.028).

Conclusions: Lung cancer patients receiving nivolumab have a certain level of risk for developing infectious diseases. In the current study, a history of diabetes mellitus was an independent risk factor for infectious disease development. Clinicians should pay attention to occult infectious diseases in patients receiving lung cancer treatment with immune checkpoint inhibitors, especially those with the history of diabetes mellitus.

Keywords: Cancer immunotherapy; Immune checkpoint inhibitor; Immune related adverse event; Infectious diseases; Nivolumab.