Impact of gut-microbiome altering drugs and fecal microbiota transplant on the efficacy and toxicity of immune checkpoint inhibitors: A systematic review

Abstract

Immune Checkpoint Inhibitors (ICIs) have improved survival in many patients with advanced cancers, however, many patients develop serious and often permanent immune-related adverse events (irAEs). Recent studies have shown that alterations in commensal gut bacteria, also known as gut dysbiosis, may lead to an increased risk of irAEs. This systematic review includes studies published between January 1, 2015, to April 10, 2021, written in the English language, which described an association between antibiotics/other concomitant medications, or fecal microbiota transplant (FMT), or both, on ICI efficacy and/or incidence of irAEs. In total, 1204 studies were identified that were published between January 1, 2015–April 10, 2021, and 28 met the inclusion criteria. Of these 28 articles, 22 examined the effect of antibiotics and other gut-microbiome altering drugs on ICI efficacy, whereas 6 studies examined the effect of FMT on ICI efficacy and irAE reduction. 21 of the 22 articles that examined the effect of antibiotics showed a negative impact on overall survival (OS) and/or progression free survival (PFS). All the studies (6) that examined FMT showed a beneficiary effect in terms of restoring ICI efficacy and/or decreasing incidence or severity of irAEs. Overall, the use of antibiotics had a significant negative impact on patients’ response to ICI treatment. Therefore, the use of antibiotics in this patient population should be carefully considered, taking into account potential risks and benefits. Restoration of a healthy gut microbiota through FMT is a potentially beneficial prospective approach that could be used to enhance therapeutic efficacy of ICIs and ameliorate irAEs.