{
  "abstract": "Background Immunotherapy has revolutionized the treatment landscape of solid tumors. Yet, many patients still face disease progression. 1 Recently, evidence has shown that intestinal microbiome composition of patients treated with immunotherapy differs between responders and non-responders.2 In this context, fecal microbiota transplantation (FMT) has emerged as a potential strategy to improve patients‘ response to treatment.3–15 We performed a systematic review and meta-analysis aimed at evaluating the efficacy of FMT in cancer patients receiving immunotherapy.Methods We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search was conducted across PubMed, Embase, and Cochrane up to May 2025, focusing on clinical trials (CTs) exploring immunotherapy plus FMT in solid tumors. Our primary outcomes of interest were objective response rate (ORR) and disease control rate (DCR). All analyses were carried out using R software (version 4.3.2).Results We included 12 CTs with 180 cancer patients receiving immunotherapy plus FMT. The majority were phase I studies. Most patients had advanced melanoma (28%), renal cell carcinoma (25%) and non small cell lung cancer (19.5%) and received either anti-PD1 therapy concurrently with FMT as 1st line treatment (56.1%) or started FMT after disease progression following anti-PD1 therapy (43.9%). All FMT were from healthy donors or from patients who previously responded to immunotherapy. The pooled analysis of nine studies with 139 patients revealed an ORR of 33.7% (95% CI 18.1-53.9%; figure 1). Among 129 patients, 70 achieved DCR with this strategy (49.6%, 95% CI 28-71.4%). The clinical benefit rate was 43% (95% CI 7.3-88%) across 28 patients. The subanalysis of patients who received immunotherapy plus FMT as first line revealed an ORR and DCR of 59% (95% CI 47.9-69.6%) and 80.4% (95% CI 67.3-89.1%), respectively, compared to an ORR of 15.9% (95% CI 8.8-27.1%) and DCR of 30.9% (95% CI 17.5-48.6%) in patients receiving FMT after disease progression on first-line immunotherapy (p<0.0001; figure 2). Progression-free survival (PFS) was described in 3/12 studies, and for this study was not pooled for analysis. The median PFS varied from one to 14 months across studies.Conclusions The addition of FMT to PD-1 inhibitors in cancer patients appears to be an effective strategy to improve sensitivity to immune-checkpoint therapy. Future studies are needed to further establish the survival benefit of this intervention in larger populations.References Piper M, Kluger H, Ruppin E, et al. Immune resistance mechanisms and the road to personalized immunotherapy. Am Soc Clin Oncol Educ Book 2023;43:e390290.McCulloch JA, Davar D, Rodrigues RR, et al. Intestinal microbiota signatures of clinical response and immune-related adverse events in melanoma patients treated with anti-PD-1. Nat Med. 2022;28:545–556.Arielle Elkrief, et al. Gut microbiota in immuno-oncology: a practical guide for medical oncologists with a focus on antibiotics stewardship. Am Soc Clin Oncol Educ Book 2025;45:e472902.Ullern A, Garborg KK, Holm K, Johnsen PH, Hov JR, Kyte JA. 669 MITRIC: microbiota transplant to cancer patients progressing on immunotherapy using feces from clinical responders. Journal for ImmunoTherapy of Cancer 2024;12. https://doi.org/10.1136/jitc-2024-SITC2024.0669Baruch EN, Higbie VS, Damania AV, et al. 1266 The gut microbiome enhances anti-PD-1 efficacy in a tumor-agnostic manner: results from a phase II trial of fecal microbiota transplantation and anti-PD-1 re-induction in MSI-H refractory cancers. Journal for ImmunoTherapy of Cancer 2024;12. https://doi.org/10.1136/jitc-2024-SITC2024.1266Huang MJ, et al. P2.11A.23 fecal microbiota transplantation plus rechallenging immunotherapy in patients with advanced non small cell lung cancer: an exploratory study. Journal of Thoracic Oncology 2024;19(10):S262–S263. https://doi.org/10.1016/j.jtho.2024.09.472Ciccarese C, et al. LBA77 Fecal microbiota transplantation (FMT) versus placebo in patients receiving pembrolizumab plus axitinib for metastatic renal cell carcinoma: preliminary results of the randomized phase II TACITO trial. Annals of Oncology 2024;35:S1264. 10.1016/j.annonc.2024.08.2320Elkrief A, et al. 1068P phase II trial of fecal microbiota transplantation (FMT) plus immune checkpoint inhibition (ICI) in advanced non-small cell lung cancer and cutaneous melanoma (FMT-LUMINate). Annals of Oncology 2024;35:S707–S708. 10.1016/j.annonc.2024.08.1126Ya Xue, et al. Fecal microbiota transplantation combined with anti-PD-(L)1 inhibitors as first-line maintenance therapy for advanced gastric and non small cell lung cancer. JCO 2024;42:2646–2646. https://doi.org/10.1200/JCO.2024.42.16_suppl.2646Fernandes R, Rajeh A, Lenehan JG, Ernst S, Winquist E, Baines K, et al. 1475 combination of LND101, a healthy donor microbiome transplantation product, to doublet immunotherapy or immunotherapy combined with targeted therapy in metastatic renal cell carcinoma patients. Journal for ImmunoTherapy of Cancer 2024;12. https://doi.org/10.1136/jitc-2024-SITC2024.1475Kim Y, Kim G, Kim S, et al. Fecal microbiota transplantation improves anti-PD-1 inhibitor efficacy in unresectable or metastatic solid cancers refractory to anti-PD-1 inhibitor. Cell Host Microbe. 2024 Aug 14;32(8):1380–1393.e9. doi: 10.1016/j.chom.2024.06.010. Epub 2024 Jul 25. PMID: 39059396. 10.1016/j.chom.2024.06.010Davar D, Dzutsev AK, McCulloch JA, et al. Fecal microbiota transplant overcomes resistance to anti–PD-1 therapy in melanoma patients. Science 2021;371:595–602. DOI: https://doi.org/10.1038/s41591-023-02453-xBaruch EN, Youngster I, Ben-Betzalel G, et al. Fecal microbiota transplant promotes response in immunotherapy-refractory melanoma patients. Science 2021;371:602–609. DOI: 10.1126/science.abf33Routy B, Lenehan JG, Miller WH, et al. Fecal microbiota transplantation plus anti-PD-1 immunotherapy in advanced melanoma: a phase I trial. Nat Med. 2023;29:2121–2132. DOI: 10.1126/science.abb5920Yifan Zhang, Xiaomin Xu, Shulin Wang, et al. Fecal microbiota transplantation promotes immunotherapy sensitivity in refractory gastrointestinal cancer patients: open label, single-arm, single center, phase 1 study. medRxiv 2024.08.21.24312340; DOI: https://doi.org/10.1101/2024.08.21.24312340Abstract 1134 Figure 1Abstract 1134 Figure 2",
  "authors": [
    {
      "affiliations": [
        "University of Fortaleza (UNIFOR), Fortaleza, Ceara, Brazil"
      ],
      "name": "Wellington Carneiro"
    },
    {
      "affiliations": [
        "University of Virginia Comprehensive Cancer Center, Charlottesville, VA, USA"
      ],
      "name": "Isabella Michelon"
    },
    {
      "affiliations": [
        "UNIFESP, São Paulo, São Paulo, Brazil"
      ],
      "name": "Anderson Simões"
    },
    {
      "affiliations": [
        "Jordan University of Science and Technology, Ar Ramtha, Irbid, Jordan"
      ],
      "name": "Khalid Taha"
    },
    {
      "affiliations": [
        "University of Virginia, Charlottesville, VA, USA"
      ],
      "name": "Ludimila Cavalcante"
    }
  ],
  "title": "1134 Outcomes of fecal microbiota transplantation (FMT) in cancer patients receiving immunotherapy: a systematic review and meta-analysis",
  "uid": "be805b40-016e-52af-8d43-854d706c8760"
}