Aims: The purpose of this study was to determine the presence of a pooled objective response rate (ORR) of fecal microbiota transplantation (FMT) combined with immune checkpoint inhibitor (ICI) therapy and compare ORR between ICI naive and previous ICI exposed patients.
Methods: 21 studies were obtained from a previous systematic review of 45 studies. These studies were chosen as they evaluated ORR after FMT plus ICI therapy. From these, 12 prospective, single arm studies (six phase I/Ib, four phase II, one phase II/III, one cohort study) with patient level responder counts were pooled using a random effects DerSimonian-laird model. Reported treatment history was used to categorize ICI naive or previous ICI exposed patients. Heterogeneity was assessed using I2 and subgroup differences were tested using Cochran’s Q.
Results: ORR ranged from 20%-80% in the ICI naive subgroup from individual studies, compared to 8% to 33% in the ICI refractory subgroup. Pooled ORR for FMT plus ICI was 40% (95% CI, 26%-55%) across the 12 studies (176 patients: 115 ICI naive, 61 previously ICI exposed), with substantial heterogeneity (I2 = 69%). ORR was significantly higher for ICI naive patients (55%, 95% CI, 35%-73%) compared to the previous ICI exposed patient population (23%, 95% CI, 14%-36%; P=0.009).
Conclusions: This study shows prior exposure to ICI therapy may influence response to FMT. There are a few limitations to this study such as small sample sizes and variable source FMT. Further trials are required to understand the role of FMT in modulating ICI response in both ICI naive and ICI exposed cohorts.