Pooled allogeneic faecal microbiota MaaT013 for steroid-resistant gastrointestinal acute graft-versus-host disease: a single-arm, multicentre phase 2 trial

作者：Florent Malard, Michael L. Loschi, Anne Huynh, Thomas Cluzeau, Sarah Guenounou, Faézeh Legrand, Léonardo Magro, Corentin Orvain, A Charbonnier, Marta Panz-Klapuch, Déborah Desmier, Jean-Baptiste Méar, Jérôme Cornillon, Christine Robin, Étienne Daguindau, Karin Bilger, Maria J. G. T. Vehreschild, Patrice Chevallier, Hélène Labussière‐Wallet, Clémence Mediavilla, Marie‐Anne Couturier, Claude‐Eric Bulabois, Vincent Camus, Sylvain Chantepie, Patrice Céballos, Béatrice Gaugler, Ernst Holler, Joël Doré, Emmanuel Prestat, Cyrielle Gasc, Émilie Plantamura, Mohamad Mohty · 发表于：EClinicalMedicine · 年份：2023 · DOI：10.1016/j.eclinm.2023.102111 · 被引用次数：56 · 研究领域：Gut microbiota and health、Hematopoietic Stem Cell Transplantation、Clostridium difficile and Clostridium perfringens research

Background: -host disease (GI-aGvHD) to respond to steroid therapy is associated with limited further therapeutic options. We aimed to assess the safety and efficacy of the first-in-human use of the pooled allogeneic faecal microbiota, MaaT013, for the treatment of steroid-refractory GI-aGvHD. Methods: This prospective, international, single-arm, phase 2a study reports clinical outcomes from a 24-patient cohort with grade III-IV, steroid refractory GI-aGvHD treated with the pooled allogeneic faecal microbiota MaaT013. MaaT013 involved pooling faecal matter from 3 to 8 screened donors then transplanting the pooled batches into patients to treat GI-aGVHD. The 24 patients were treated in the HERACLES study (Aug 2018 to Nov 2020) at 26 sites in Europe and an additional 52 patients were treated in a compassionate use/expanded access program (EAP) in France (July 2018 to April 2021). The primary endpoint was GI response at day 28, defined as the proportion of patients with GI-aGvHD who had a complete response (CR) or very good partial response (VGPR). GvHD grading and staging were assessed according to the revised Glucksberg criteria. Adverse events and severe adverse events were monitored for 6 months and 12 months, respectively. The HERACLES study was registered with ClinicalTrials.gov (NCT03359980). Findings: Compared with single donors, MaaT013 is characterised by higher microbial richness and reduced variability across batches. At day 28 (D28), the GI-overall response rate (OR...