image: FLOW DIAGRAM OF IDENTIFICATION OF STUDIES VIA DATABASES AND REGISTERS. CREDIT: THE AUTHORS.
Credit: The authors.
In light of the potential and challenges surrounding the combination of FMT and ICIs in tumor immunotherapy, this study aims to comprehensively evaluate the clinical efficacy, safety, and potential predictive factors of this combination therapy through a systematic literature review and meta-analysis. Specifically, this study will focus on the therapeutic efficacy, survival outcomes, safety. Furthermore, subgroup analysis will focus on how different factors, including ICI strategies, FMT donor sources, FMT administration routes, and tumor types that influence treatment outcomes. Through this comprehensive analysis, we aim to provide high-quality, evidence-based insights into the application of FMT in immunotherapy to support clinical decision-making, future research design, and the development of individualized treatment strategies.
We conducted a comprehensive search of relevant studies available up to September 30, 2024 to analyze the clinical efficacy and safety of combining FMT with ICIs in cancer treatment. A total of 10 studies involving 164 patients with solid tumors were included.
The pooled ORR was 43% (95% CI: 0.35-0.51), CR rate was 12% (95%CI: 0.07-0.19), and PR rate estimate was 34% (95%CI: 0.26-0.42). Subgroup analysis revealed that the combination of anti-PD-1 and anti-CTLA-4 therapies was associated with a significantly higher ORR (60%) compared to anti-PD-1 monotherapy (37%; P = 0.01). The heterogeneity test of CR and PR indicated low to moderate heterogeneity across studies. Subgroup analyses of PR and CR showed that comparisons between groups were largely consistent with those for ORR.The incidence of grade 1-2 adverse events (AEs) was 42% (95% CI: 0.32-0.52), while grade 3-4 AEs occurred in 37% of patients (95% CI: 0.28-0.46).
Despite the aforementioned limitations, this meta-analysis provides preliminary evidence supporting the application of FMT combined with ICIs in the treatment of advanced or refractory tumors. The findings indicate that this combination therapy may offer significant clinical benefits, including improved objective response and disease control rates, with an acceptable safety profile. In the future, to further investigate the potential of FMT in the therapeutic application of ICIs, we should comprehensively examine the interactions among microbial specific properties, metabolites, colonization environments, immunopharmaceutical agents, tumorigenicity, and dietary strategies. Additionally, artificial intelligence algorithms should be leveraged to analyze human microbiome sequencing data, extracting key information for clinical applications. This interdisciplinary integration and cross-disciplinary collaboration will pave the way for significant breakthroughs in precision tumor therapy.
Article Title
Microbiota boost immunotherapy? A meta-analysis dives into fecal microbiota transplantation and immune checkpoint inhibitors.
COI Statement
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.