Purpose: Gastrointestinal (GI) microbiome modulators, such as fecal microbiome transplants (FMTs), are being considered as supplements to standard immune checkpoint inhibitor (ICI) treatment to improve efficacy. This systematic review aims to assess the study design and outcomes of clinical trials that use FMTs to enhance ICI treatment.
Methods: Systematic literature searches were conducted on PubMed and Embase using search terms that included names of ICIs and gastrointestinal microbiome. A first search identified interventional trials, and the second search identified interventional, retrospective, and observational studies.
Results: The search for interventional trials produced 205 articles, 3 of which met the inclusion criteria. All studies had sample sizes ranging between 10 and 30 participants. 2 of the studies were single-arm studies with no control arm. One study reported an overall response rate (ORR) of 3 out of 15 (20%), a median progression-free survival (PFS) of 3 months, and a median overall survival (OS) of 7 months. The second study reported 1 complete response out of 10 (10%) and 2 partial responses out of 10 (20%). The third study reported an ORR of 58% vs. 20%, a median PFS of 12.7 months vs. 2.5 months in patients receiving nivolumab-ipilimumab plus CBM588 compared with patients receiving nivolumab-ipilimumab alone respectively, and an undefined median OS.
Conclusion: Current studies on the microbiome modulators with ICI use are limited in study design. Future clinical trials should be randomized, use larger sample sizes, and use an appropriate control arm to better ascertain the clinical effect of the GI microbiome on ICI treatment.
Keywords: Fecal microbiome transplants; GI microbiome; Gastrointestinal microbiome; Immune checkpoint inhibitor; Ipilimumab; Nivolumab; Pembrolizumab; Systematic review.
© 2023. The Author(s).