Welcome to PracticeUpdate! We hope you are enjoying access to a selection of our top-read and most recent articles. Please register today for a free account and gain full access to all of our expert-selected content.
Already Have An Account? Log in Now
Fecal Microbiota Transplant Promotes Response in Immunotherapy-Refractory Melanoma Patients
TAKE-HOME MESSAGE
-
In this phase I study, 10 patients with anti–PD-1–refractory metastatic melanoma were treated with fecal microbiota transplantation (FMT) from 2 donors who had a complete response to immune checkpoint inhibitor (ICI) therapy. The combination of FMT and nivolumab resulted in 3 responses, including 1 complete response in a patient with no prior response to ICI treatment. FMT was associated with improvement in the nature of immune cell infiltrates and gene expression profiles in the gut and in the tumor.
- Modulation of the gut microbiota may impact the response to cancer therapy.
abstract
This abstract is available on the publisher's site.
Access this abstract nowThe gut microbiome has been shown to influence the response of tumors to anti-PD-1 (programmed cell death-1) immunotherapy in preclinical mouse models and observational patient cohorts. However, modulation of gut microbiota in cancer patients has not been investigated in clinical trials. In this study, we performed a phase 1 clinical trial to assess the safety and feasibility of fecal microbiota transplantation (FMT) and reinduction of anti-PD-1 immunotherapy in 10 patients with anti-PD-1-refractory metastatic melanoma. We observed clinical responses in three patients, including two partial responses and one complete response. Notably, treatment with FMT was associated with favorable changes in immune cell infiltrates and gene expression profiles in both the gut lamina propria and the tumor microenvironment. These early findings have implications for modulating the gut microbiota in cancer treatment.
Additional Info
Disclosure statements are available on the authors' profiles:
Fecal Microbiota Transplant Promotes Response in Immunotherapy-Refractory Melanoma Patients
Science 2021 Feb 05;371(6529)602-609, EN Baruch, I Youngster, G Ben-Betzalel, R Ortenberg, A Lahat, L Katz, K Adler, D Dick-Necula, S Raskin, N Bloch, D Rotin, L Anafi, C Avivi, J Melnichenko, Y Steinberg-Silman, R Mamtani, H Harati, N Asher, R Shapira-Frommer, T Brosh-Nissimov, Y Eshet, S Ben-Simon, O Ziv, MAW Khan, M Amit, NJ Ajami, I Barshack, J Schachter, JA Wargo, O Koren, G Markel, B BoursiFrom MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
Oncology
These two proof-of-concept studies highlight the potential application of FMT to augment the response of cancer patients to immunotherapies. FMT has already been demonstrated to be successful in the setting of recurrent Clostridioides difficile infection and is now considered a standard-of-care therapy. Yet, the specific underlying components of FMT that contribute to favorable responses for C. difficile infection, or immunotherapy treatment in cancer patients, remain to be defined. To date there does not appear to be a defined bacterial consortium, or functional characteristics of a donor microbiota, that are consistently associated with improved immunotherapy response in cancer patients or mouse models. The challenge in the field is determining what donor and recipient features contributes to a favorable outcome for FMT or indeed an unfavorable one. Nevertheless, these studies provide exciting and compelling evidence that FMT is beneficial for a subset of cancer patients that are refractory to immunotherapy, patients that may have few alternative treatment options. The difficultly moving forward will be determining the level of mechanistic insight that is needed before incorporation of FMT more broadly in the treatment of such patients.