Pilot study of intestinal microbiome alteration with resistant potato starch (RPS) in patients (pts) treated with dual immune checkpoint inhibitors (ICI).

Abstract

e24120 Background: The intestinal microbiome is associated with ICI efficacy & toxicity; whether it can be altered to improve clinical outcome is unknown. RPS is digested by colonic microbiota to make anti-inflammatory metabolites & maintain mucosal barrier. Immune-related adverse events (irAE): diarrhea/colitis are common with dual ICI, cause premature treatment discontinuation. We evaluated safety & feasibility of dietary intervention with RPS in pts receiving ipilimumab (I) + nivolumab (N). Methods: Single-arm study of RPS 20g PO daily x 3, then 20g PO BID. RPS began 5-7 days before starting dual ICI (up to 4 cycles: I 3 mg/kg + N 1 mg/kg) & until 3 wks after last ICI or grade (Gr) ≥3 diarrhea/colitis, whichever first. We analyzed safety, feasibility, rates of diarrhea/colitis, intestinal microbiome composition changes via 16S ribosomal RNA stool sequencing. Results: 12 pts enrolled;1 pt withdrew consent prior to RPS start (n=11); median age 59 yo (range 25-69). 45.5% pts completed 4 cycles I/N; 45.5% completed < 4 doses of I/N due to irAE or possible irAE. 9 pts (81.8%) completed RPS course with high adherence (94.6% dose taken). 1 stopped RPS for unrelated Gr 3 diarrhea (irAE); 1 stopped RPS for unrelated GI hemorrhage, H pylori. RPS was well tolerated with no attributable adverse events or dose reductions. Diarrhea occurred in 7 pts (63.6%): 2 Gr 3, 4 treated with steroids-similar to published rates (Table). There were increases in 2 species of intestinal Bifidobacterium from baseline after RPS administration. Conclusions: Alteration of intestinal microbiota with RPS was feasible, well tolerated & safe in pts treated with I/N. Additional correlative metabolomic studies are ongoing. Further investigation is warranted in a larger population. Clinical trial information: NCT04552418 . RPS adherence & presence of diarrhea (D) or colitis (C). Pt n=11 #RPS days %RPS taken #doses I/N Reason RPS stop D/C(Gr) D/C 2/2 irAE? D/C treated w/ steroids? 1 76 96 2 Off ICI N N N 2 110 99.5 4 CompletedICI N N N 3 68 93.2 2 Off ICI D(1), persistent Y Y 4 48 85 2 Off ICI N N N 5 93 NE* 3 Off ICI D(1) N N 6 97 85.9 4 CompletedICI N N N 7 89 98.9 4 CompletedICI (a)D(2)(b)D(1) NY NY 8 42 97.5 2 irAE: DG3 D(3) Y Y^ 9 109 90 4 CompletedICI D-C(3) Y Y^ 10 112 100 4 Completed ICI D(2) P N 11† 6 100 1 GI bleed, H pylori D(1) N N †Stopped RPS after GI bleed 2/2 duodenal neuroendocrine tumor before 1st dose ICI. *NE=Not evaluable: missing data. ^infliximab. Y=yes, N=no, P=possible.