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3553 Pooled Fecal Allogenic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease : Results from Early Access Program in Europe

Program: Oral and Poster Abstracts
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Poster II
Hematology Disease Topics & Pathways:
Biological therapies, drug development, Therapies, Transplantation
Sunday, December 10, 2023, 6:00 PM-8:00 PM

Florent Malard, MD, PhD1*, Michael Loschi, MD2*, Thomas Cluzeau, MD, PhD3, Faezeh Legrand, MD4*, Jean-Baptiste Méar, MD5*, Faustine Lhomme, MD6*, Anne Huynh, MD7*, Sarah Guenounou, MD8*, Cécile Borel, MD9*, Déborah Desmier, MD10*, Niels Moya, MD11*, Amandine Charbonnier, MD12*, Delphine Lebon13*, Hélène Labussière-Wallet14*, Corentin Orvain15*, Sylvain Chantepie, MD16*, Martin Carre, MD17*, Vincent Camus, MD18*, Marie-Anne Couturier, MD19*, Jérôme Cornillon, MD20*, Patrice Chevallier, MD21, Clemence Mediavilla, MD22*, Patrice Ceballos, MD23*, David Beauvais, MD24*, Etienne Daguindau, MD25*, Karin Bilger, MD26*, Stefan Klein, MD27*, Marion Bruelle, PhD28*, Emilie Plantamura, PhD, MSc, PharmD29* and Mohamad Mohty, MD, PhD30

1Department of Clinical Hematology and Cellular Therapy, Sorbonne University, Saint Antoine Hospital, Assistance Publique - Hôpitaux de Paris, INSERM UMRs 938, Centre de Recherche Saint-Antoine (CRSA), Paris, France
2Service d’hématologie, CHU de Nice, Nice, France
3Nice University Hospital, Nice, Provence Alpes Cote d'Azur, France
4Hematology department, Institut Paoli calmettes, Marseille, FRA
5University Hospital of Rennes, Clinical hematology, Rennes, France
6Clinical Hematology, University Hospital of Rennes, RENNES, France
7Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France
8CHU de Toulouse - Institut Universitaire du Cancer de Toulouse Oncopole, Toulouse, France
9Hematology department, IUCT Oncopole, Toulouse, France
10Poitiers Hospital, Poitiers, FRA
11CHU Poitiers, Poitiers, France
12Service d’Hématologie Clinique, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, France
13Hematology Department, CHU Amiens, Amiens, France
14Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
15Hematology Department, Angers University Hospital, Angers, France
16Institut d'Hématologie, CHU de Caen, Caen, France
17Clinical Hematology Department, CHU Grenoble Alpes - Université Grenoble Alpes, Grenoble, France
18Department of Hematology, Centre Henri Becquerel, Rouen, France
19CHU Brest, BREST, France
20Département d’hématologie clinique et de thérapie cellulaire, CHU de St-Étienne, Saint-Étienne, France
21Service d'hématologie, CHU de Nantes, Nantes, France
22Hopital Haut-Leveque, Bordeaux, France
23Clinical Hematology Department, Montpellier University Hospital, MONTPELLIER, France
24Allograft department, CHRU Lille, Lille, France
25Department of Clinical Hematology, Hopital Jean Minjoz, Service d`Hématologie, Besançon, France
26Hematology, Institut de Cancerologie Strasbourg Europe (ICANS), Strasbourg, France
27Medizinische Klinik Hämatologie und Onkologie Universitätsmedizin, Mannheim, Germany
28MaaT Pharma, Lyon, France
29MaaT Pharma, LYON, France
30Saint-Antoine Hospital, Sorbonne University, Paris, France


Acute Graft-versus-host disease (aGvHD) is a major source of mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Fecal microbiotherapy has shown promising results in several pilot studies in patients with refractory gastrointestinal (GI)-aGvHD. Here we report clinical outcomes from 111 patients diagnosed with steroid-refractory (SR) or dependent (SD) GI-aGvHD treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in Europe.

Patients and methods

One hundred and eleven patients (including 1 pediatric patient aged 15 years) with SR/SD GI-aGvHD (Classical n=70, late onset n=12, overlap syndrome n=16, hyper-acute n=13) were treated with MaaT013 therapy as part of Early Access Program in Europe (France and Germany). These patients had previously failed 1 to 6 systemic GvHD treatment lines (median 3; 94/111 received ruxolitinib). Most patients had grade III to IV aGvHD (9% grade II, 49% grade III aGvHD, 42% grade IV).

For each patient, a total of 3 MaaT013 administrations were planned every 7 +/- 2 days (median dose administered 3). Each dose is composed of 30 g of feces in 150 mL of suspension from 4 to 8 healthy donors administered by enema (except for 1 patient by nasogastric tube).

Treatment response was calculated among all treated patients based on aGvHD staging and grading at day 28 (D28) at the time of the EAP request.


At D28, the GI-ORR was 53%: 39 CR (35%), 15 VGPR (14%), 5 PR (5%). GI-ORR was higher in patients with lower grade aGvHD (100% in grade II, 63% in grade III, 32% in grade IV) and higher in SD versus SR (88% versus 47%). Overall response considering all organs (n=108 with 3 missing data) was 50%, including 34 CR, 16 VGPR and 4 PR.

Administration of MaaT013 in the pediatric patient was well tolerated and led to complete response of GI and skin symptoms (the patient had stage 3 skin and stage 4 GI aGvHD) up to 12 months. Symptoms of the liver were not resolved at D28 (stage 2 liver, stable disease) but improved from month 6 without additional therapy.

Overall survival (OS) was 56% at 6 months (M6) and 47% at M12. The median follow-up among surviving patients was 355 days (range, 27-731). OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=59) compared to patients in treatment failure (Non-responder, NR; n=52): 74% versus 36% at M6, 67% versus 24% at M12 (p<0.0001 log-rank test). Median survival duration in R was 293 days versus 56 days in NR.

Interestingly, in the subgroup of 38 patients previously treated with ruxolitinib as 2nd line and MaaT013 as 3rd line GI-ORR was improved being 61% D28, with 58% CR. OS at M6 was 55% and 52% at M12. OS was significantly higher in R patients, when compared to NR patients (81% versus 16% at M6 and 81% versus 8% at M12 for R and NR respectively, p<0.0001 log-rank test).

MaaT013 displays a good overall safety profile in EAP population: 29 pharmacovigilance cases were reported in 27 patients, including 18 cases that could be possibly considered related to MaaT013 either by the physician or the company: sepsis in 5 patients, bacteremia in 7 patients, rectal bleeding/ anorectal disorder in 3, C. difficile colitis in 1, E. coli osteoarthritis in 1, detection of G. silvicola in stools in 1. No pathogen transmission has been reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013 batch. Causality could not be formally excluded in these cases.

56 deaths have been reported. The cause of death was GvHD in 23 patients, severe infection in 15, relapse of underlying malignancy in 9, COVID-19 in 5, hemorrhage during surgery in 1, neurological complications post allo-HCT in 1, and cardiac arrest in 2 patients. No causality link with MaaT013 administration has been identified.


Overall, EAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD especially in patients having previously received ruxolitinib. Interestingly, response of GI-aGvHD correlates with increased overall survival, suggesting a strong favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895).

Disclosures: Malard: Therakos/Mallinckrodt: Honoraria; Sanofi: Honoraria; JAZZ Pharmaceuticals: Honoraria; Gilead: Honoraria; Novartis: Honoraria; Bristol Myers Squibb: Honoraria. Loschi: Abbvie: Honoraria; Alexion: Honoraria; Astra Zeneca: Honoraria; BMS Celgene: Honoraria; Gilead: Honoraria; GSK: Honoraria; Jazz: Honoraria; Novartis: Honoraria; Pfizer: Honoraria; Sanofi: Honoraria; Sobi: Honoraria; Takeda: Honoraria. Cluzeau: Novartis: Consultancy, Speakers Bureau; Abbvie: Consultancy, Speakers Bureau; Jazz Pharma: Consultancy, Speakers Bureau; Syros: Speakers Bureau; Keros: Speakers Bureau; Servier: Consultancy, Speakers Bureau; Incyte: Speakers Bureau; BMS: Consultancy, Speakers Bureau. Huynh: Medac: Other: Advisory board; Astellas: Other: Advisory board; Servier: Other: Advisory board; Pfizer: Other: advisory board; Jazz: Other: travel fees, advisory board; Novartis: Other: travel fees, advisory board; Neovii: Other: Advisory board. Camus: Kite-Gilead: Honoraria. Chevallier: Mallinckrodt Pharmaceuticals: Honoraria; Sanofi: Honoraria; Incyte: Honoraria, Research Funding; Takeda: Honoraria; Immedica Pharma: Honoraria; Servier: Honoraria. Mediavilla: AbbVie: Honoraria, Research Funding; Bristol Myers Squibb: Honoraria, Research Funding; Novartis: Honoraria. Klein: Novartis: Honoraria. Bruelle: MaaT Pharma: Current Employment. Plantamura: MaaT Pharma: Current Employment, Current holder of stock options in a privately-held company. Mohty: JAZZ PHARMACEUTICALS: Honoraria, Research Funding.

*signifies non-member of ASH