-Author name in bold denotes the presenting author
-Asterisk * with author name denotes a Non-ASH member
Clinically Relevant Abstract denotes an abstract that is clinically relevant.

PhD Trainee denotes that this is a recommended PHD Trainee Session.

Ticketed Session denotes that this is a ticketed session.

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

Program: Oral and Poster Abstracts
Type: Oral
Session: 722. Allogeneic Transplantation: Acute and Chronic GVHD, Immune Reconstitution: Clinical Studies Exploring the Immunobiology of HCT
Hematology Disease Topics & Pathways:
Research, Clinical Research, real-world evidence
Saturday, December 10, 2022: 10:15 AM

Florent Malard, MD, PhD1*, Michael Loschi, MD, PhD2*, Thomas Cluzeau, MD, PhD3, Faezeh Legrand, MD4*, Jean-Baptiste Mear, MD, PhD5*, Faustine Lhomme, MD, PhD6*, Sarah Guenounou, MD7*, Anne Huynh8*, Cecile Borel, MD9*, Deborah Desmier, MD10*, Niels Moya, MD11*, Amandine Charbonnier, MD12*, Delphine Lebon, MD12*, Hélène Labussière-Wallet13*, Corentin Orvain, MD, PhD14*, Sylvain Chantepie, MD15*, Claude-Eric Bulabois, MD16*, Vincent Camus, MD17*, Marie-Anne Couturier, MD18*, Jérôme Cornillon, MD19*, Patrice Chevallier, MD20, Clémence Mediavilla21*, Patrice Ceballos, MD, PhD22*, David Beauvais, MD23*, Marion Bruelle, PharmD, PhD24*, Emilie Plantamura, PhD, PharmD24* and Mohamad Mohty, MD PhD25

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
2Hematology department, CHU de Nice, Universite Cote d'Azur, Nice, France
3Département d'Hématologie Clinique, Université Côte d'Azur, CHU Nice, Nice, Provence Alpes Cote d'Azur, France
4Hematology Department, Institut Paoli-Calmettes, Marseille, France
5Clinical hematology, University Hospital of Rennes, Rennes, France
6Hematology department, CHU of Rennes, Rennes, France
7Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
8Institut Universitaire du Cancer de Toulouse-Oncopole, Toulouse, France
9Hematology Department, Institut Universitaire du Cancer de Toulouse - Oncopole, Toulouse, France
10CHU de Poitiers, Service d'Hématologie et de thérapie cellulaire, Poitiers, France
11Hematology and cellular therapy department, CHU Poitiers, POITIERS, France
12Service d’Hématologie Clinique et Thérapie cellulaire, Centre Hospitalier Universitaire d’Amiens, Amiens, France
13Clinical hematology service, Hospices Civils de Lyon, Lyon, France
14Angers University Hospital, Angers, France
15Institut d'Hématologie de Basse Normandie, Centre Hospitalier Universitaire, Caen Cedex 9, France
16Service d'Hématologie, CHU Grenoble Alpes - Université Grenoble Alpes, Grenoble, France
17Department of Clinical Hematology, Centre Henri Becquerel, Rouen, France
18Brest University Hospital, Brest, France
19Hematology department, Lucien Neuwirth Cancer Institute, Saint-Priest-en-Jarez, France
20Hematology Department, Nantes University Hospital, Nantes, France
21Saint-Antoine Hospital, AP-HP, Paris, FRA
22Hematology Department, Montpellier University Hospital, Montpellier, France, Montpellier, France
23Department of Hematology, University Hospital of Lille, Lille, France
24MaaT Pharma, Lyon, France
25EBMT Paris study office / CEREST-TC, Paris, France, Department of Hematology, Saint Antoine Hospital, Paris, France, INSERM UMR 938, Sorbonne University, Paris, France

Introduction

Acute graft-versus-host disease (aGvHD) is a major source of mortality following allogeneic hematopoietic cell transplantation (allo-HCT). Standard 1st line therapy for the treatment of aGvHD involves corticosteroids (CS). However, more than 50% of patients are refractory to CS (SR-aGvHD) and the associated mortality rate is of up to 80%. Recently, Ruxolitinib has been approved as 2nd line treatment for SR-aGvHD. However, patients with severe gastrointestinal (GI) aGvHD seem less likely to respond to Ruxolitinib and have poor outcomes with limited therapeutic options.

In this context, fecal microbiotherapy has shown promising results in several pilot studies in patients with refractory GI-aGvHD. Here we report clinical outcomes from 81 patients diagnosed with SR or dependent (SD) GI-aGvHD treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in France.

Methods

81 patients with SR/SD GI-aGvHD (Classical n=62, late onset n=12, overlap syndrome n=7) were treated with MaaT013 as part of an EAP in France. These patients had failed 1 to 6 prior systemic GvHD treatment lines (median 2; 66/81 received Ruxolitinib). Most patients had grade III-IV aGvHD (11% grade II, 51% grade III, 38% grade IV).

For each patient, a total of 3 MaaT013 administrations were planned every 7 +/- 2 days. Each dose comprised 30g of feces in 150 mL of diluent, 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.

Results

At D28, the GI-overall response rate (ORR) was 56%: 30 complete response (CR, 37%), 11 very good response rate (VGPR, 14%), 4 partial response (PR, 5%). The GI-ORR was higher in patients with lower grade aGvHD (89% in grade II, 66% in grade III, 32% in grade IV) and higher in SD versus SR patients (92% versus 49%). Including skin and liver symptoms (n=78), response rate was 49%, including 24 CR, 11 VGPR and 3 PR and inversely correlated with aGvHD initial grade (88% in grade II, 55% in grade III, 30% in grade IV).

Overall survival (OS) was 51% at 6 months (M6) and 39% at M12. The median follow-up among surviving patients was 355 days (range, 53-731). OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=45) compared to patients in treatment failure (Non-responder, NR; n=35): 69% versus 28% at M6, 59% versus 14% at M12, respectively. Median survival duration in R was 451 days versus 32 days in NR.

Interestingly, aGvHD response was improved in the subgroup of 31 patients previously treated with Ruxolitinib as 2nd line and MaaT013 as 3rd line (65% D28 GI-ORR, OS M6 55% and 49% M12 and 74% versus 15% at M6 and 74% versus 0% at M12 for R and NR respectively).

MaaT013 displayed a good overall safety profile in the EAP population: 20 pharmacovigilance cases were reported in 18 patients: sepsis in 11 patients, C. difficile colitis in 2, E. coli osteoarthritis in 1, G. silvicola in stools from 1, P. aeruginosa sinusitis in 1, appearance of air bubbles in the mesorectum in 1, respiratory distress in 1. No pathogen transmission was 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.

The overall incidence of bacteremia (14%) remains low, compared to an incidence of 31% to 74% in bloodstream infections reported in patients with GI-aGvHD. This suggests that fecal microbiotherapy may have a protective effect on bacterial translocation, but this needs to be confirmed in further clinical trials.

47 deaths have been reported; the cause of which was GvHD in 21 patients, severe infection in 13, relapse of underlying malignancy in 6, COVID-19 in 3, 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.

Conclusion

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, GI-response to aGvHD correlates with increased OS, 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; Astellas: Honoraria; JAZZ pharmaceuticals: Honoraria; Biocodex: Honoraria; Janssen: Honoraria; Takeda: Honoraria; Novartis: Honoraria; Gilead: Honoraria; Celgene-BMS: Honoraria. Cluzeau: BMS/Celgene, Novartis, Jazz: Consultancy, Speakers Bureau; AbbVie, Astellas, Servier: Speakers Bureau. Chevallier: Pfizer: Research Funding; Incyte: Research Funding; Abbvie: Honoraria; Takeda: Honoraria; Jazz Pharmaceuticals: Honoraria. Beauvais: Gilead: Honoraria. Bruelle: MaaT Pharma: Current Employment. Plantamura: MaaT Pharma: Current Employment. Mohty: Gilead: Honoraria; GSK: Honoraria; Pfizer,: Honoraria; Adaptive Biotechnologies: Honoraria; Oncopeptides: Honoraria; Astellas: Honoraria; Novartis: Honoraria; Takeda: Honoraria; Amgen: Honoraria; Jazz Pharmaceuticals: Honoraria, Research Funding; Celgene: Honoraria; Bristol Myers Squibb: Honoraria; Sanofi: Honoraria, Research Funding; Janssen: Honoraria, Research Funding.

*signifies non-member of ASH