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4903 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 and Immune Reconstitution: Poster III
Hematology Disease Topics & Pathways:
Drug development, Clinical Research, GVHD, Diseases, Immune Disorders, Treatment Considerations, Biological therapies, Clinical procedures, Biological Processes, Microbiome
Monday, December 9, 2024, 6:00 PM-8:00 PM

Florent Malard, M.D., Ph.D.1*, Michael Loschi, MD, PhD2*, Thomas Cluzeau, MD, PhD3*, Raynier Devillier, MD, PhD4*, Faezeh Legrand, MD5*, Amandine Charbonnier, MD6*, Delphine Lebon, MD7*, Anne Huynh, MD8*, Cecile Borel, MD9*, Jean-Baptiste Méar, MD10*, Faustine Lhomme, MD11*, Hélène Labussière-Wallet, MD12*, Déborah Desmier, MD13*, Niels Moya, MD14*, Martin Carré, MD15*, Jérôme Cornillon16*, Vincent Camus, MD, PhD17*, Patrice Ceballos, MD18*, Francesco Saraceni, MD19*, Corentin Orvain20*, Sylvain Chantepie, MD21*, Jakob Daniel Rudzki22*, Marie-Anne Couturier, MD23*, Patrice Chevallier, MD, PhD24, Clemence Mediavilla, MD25*, Gabrielle Roth-Guepin, MD26*, David Beauvais, MD27*, Etienne Daguindau, MD28*, Karin Bilger, MD29*, Stefan A. Klein, MD30*, Pedro Chorao, MD31*, Sarah Altmeyer, MD32*, Francesca Patriarca, MD33*, Marion Bruelle34*, Emilie Plantamura, PhD, MSc, PharmD35*, Gianfranco Pittari, MD PhD36* and Mohamad Mohty, MD, PhD37

1Sorbonne Université, Hôpital Saint-Antoine, AP-HP, Service d'Hématologie Clinique et Thérapie Cellulaire,Centre de Recherche Saint-Antoine UMRs938, Paris, France
2Hematology Department, Nice University Hospital, Nice, France
3Hematology Department, Nice University Hospital, Cote d’Azur University, Nice, France
4Hematology and Transplantation, Institut Paoli-Calmettes, Aix Marseille University, Marseille, France
5Hematology department, Institut Paoli calmettes, Marseille, FRA
6Clinical Hematology Department, Amiens-Picardie University Hospital, Amiens, France
7Service d’Hématologie Clinique, Centre Hospitalier Universitaire Amiens-Picardie, Amiens, FRA
8Hematology Department, Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France
9Service d'Hématologie, Institut Universitaire du Cancer Toulouse - Oncopole, Toulouse, France
10Hematology Clinic, Rennes University Hospital, Rennes, France
11Clinical Hematology, University Hospital of Rennes, RENNES, France
12Hôpital Lyon Sud, Hospices Civils de Lyon, Pierre-Bénite, France
13Hematology and cellular therapy department, University Hospital of Poitiers, Poitiers, FRA
14Hematology department & CIC 1402, Poitiers University Hospital, Poitiers, France
15Département d'Hématologie, CHU de Grenoble Alpes, Grenoble, France
16Département d'hématologie Clinique et de Thérapie Cellulaire, CHU Saint-Etienne, Saint-Etienne, France
17Centre Henri Becquerel, Department of Hematology, Rouen, France
18Clinical Hematology Department, Montpellier University Hospital, Saint Eloi Hospital, MONTPELLIER, France
19Hematology and Stem Cell Transplant, Ospedali Riuniti Torrette di Ancona, Ancona, Italy
20Univ Angers, Nantes Université, CHU Angers, Inserm, CNRS, CRCI2NA, Angers, France
21Basse-Normandie Institute of Hematology, CHU de Caen, Caen, France
22Department for Hematology and Oncology, Internal Medicine V, Medical University Innsbruck (MUI), Innsbruck, Austria
23Department of Hematology, CHRU Brest, BREST, France
24Hematology Department, Nantes University Hospital, Nantes, France
25Hematology Department, CHU de Bordeaux, Bordeaux, France
26Department of Clinical Hematology, CHRU Nancy, Vandoeuvre Les Nancy, France
27Hematology Department., CHRU Lille, Lille, FRA
28Department of Clinical Hematology, Hopital Jean Minjoz, Service d'Onco-hématologie, Besançon, France
29Hematology, Institut de Cancerologie Strasbourg Europe (ICANS), Strasbourg, France
30Hämatologie und Onkologie, Medizinische Klinik, Universitaetsmedizin Mannheim, Mannheim, Germany
31Hematology Department, Hospital Universitari i Politècnic La Fe, Valencia, Spain
32Department of Oncology, Hematology, Clinical Immunology and Rheumatology, Saarland University Medical Center, Homburg/Saar, Germany
33Division of Hematology and Stem Cell Transplantation, Azienda Sanitaria Universitaria Friuli Centrale, Udine, Udine, Italy
34MaaT Pharma, Lyon, AL, France
35MaaT Pharma, LYON, France
36MaaT Pharma, Lyon, France
37Sorbonne University, Hôpital Saint-Antoine, and INSERM UMRs938, Paris, France

Introduction

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 long-term clinical outcomes of 154 patients diagnosed with refractory GI-GvHD treated with the pooled allogeneic microbiotherapy MaaT013 within an Early Access Program (EAP) in Europe.

Patients and methods

One hundred and fifty four patients (incl. two pediatric patients aged 12 and 15years) with steroid-refractory (SR) or -dependent (SD) GI-aGvHD (classical n=93, late onset n=16, chronic or overlap syndrome n=25, hyperacute n=20) were treated with MaaT013 as part of the EAP in Europe (France, Germany, Spain, Italy, Austria). These patients had previously failed 1 to 6 systemic aGvHD treatment lines (median 3; 134/152 received ruxolitinib). Most patients had grade III to IV aGvHD (13% grade II, 47% grade III, 40% grade IV).

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

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

Results

At D28, the GI-overall response rate (ORR) was 51%: 46 complete response (CR 30%), 23 very good partial response (VGPR 15%), 9 partial response (PR 6%). GI-ORR was higher in grade II & III GvHD patients compared to grade IV (65% in grade II, 64% in grade III, 30% in grade IV) and higher in SD versus SR (81% versus 45%). ORR considering all organs (n=154) was 49%, including 41 CR, 19 VGPR and 15 PR.

At D56, GI-ORR was 44% with 50 CR, 13 VGPR and 3 PR, ORR was 42% with 47 CR, 12 VGPR and 5 PR (n=151).

Administration of MaaT013 in the two pediatric patients was well tolerated. One patient was in VGPR at D28 (baseline grade IV, stage 0 skin and liver, stage 4 GI-aGVHD), the other was in complete response of GI and skin symptoms up to 12 months (baseline grade IV, stage 3 skin, stage 2 liver, stage 4 GI) but liver symptoms were not resolved at D28 (stage 2 liver, stable disease). Liver stage improved from month 6 (M6) without additional therapy.

Overall survival (OS) was 53% at M6, 47% at M12, and 42% at M24. The median follow-up among surviving patients was 418 days (range, 27-1644). OS was significantly higher in patients achieving at least GI-PR at D28 (Responder, R; n=78) compared to patients in treatment failure (Non-responder, NR; n=76): 73% versus 34% at M6, 68% versus 24% at M12 and 58% versus 24% at M24 (Log-rank test p<0.0001). Median survival duration in R was 290 days versus 71 days in NR.

Interestingly, in the subgroup of 58 patients previously treated with ruxolitinib as 2nd line and MaaT013 as 3rd line GI-ORR was improved being 59% at D28 (48% CR) and 54% at D56 (53% CR). ORR was 55% (43% CR) at D28 and 56% (53% CR) at D56. OS was 54% at M6, 49% at M12, and 40% at M24. OS was significantly higher in R patients, when compared to NR patients (79% versus 17% at M6, 75% versus 11% at M12, 61% versus 11% at M24) for R and NR, respectively, Log-rank test p<0.0001). Median survival duration in R was 444 days versus 42 days in NR.

MaaT013 displayed a good overall safety profile in the EAP population: 37 serious pharmacovigilance cases were reported in 34 patients, including 24 cases reported in 23 patients considered possibly related to MaaT013 either by the physician or the company: infections/ bacteremia in 13 patients, sepsis in 6, rectal bleeding/ anorectal disorder in 3, C. difficile colitis in 1.

83 deaths have been reported. The causes of death were GvHD in 34 patients, severe infection in 30 (incl 5 COVID-19), relapse of underlying malignancy in 11, hemorrhage in 2, neurological complications in 2, cardiac arrest in 2, acute respiratory distress in 1 and natural death in 1.

Conclusion

Overall, EAP clinical data showed that MaaT013 was a safe and effective treatment of refractory GI-aGvHD especially in patients having previously received ruxolitinib. Interestingly, the response to MaaT013 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: Beauvais: Kite/Gilead: Honoraria, Speakers Bureau. Bruelle: MaaT Pharma: Current Employment, Current equity holder in publicly-traded company. Plantamura: MaaT Pharma: Current Employment, Current equity holder in publicly-traded company. Pittari: Autolus Therapeutics: Current equity holder in publicly-traded company, Ended employment in the past 24 months; MaaT Pharma: Current Employment, Current equity holder in publicly-traded company. Mohty: Takeda: Honoraria; Stemline Menarini: Honoraria; Jazz: Consultancy, Honoraria, Research Funding, Speakers Bureau; BMS: Consultancy, Honoraria; Novartis: Honoraria; GSK: Honoraria; Pfizer: Consultancy, Current holder of stock options in a privately-held company, Honoraria, Research Funding, Speakers Bureau; Amgen: Honoraria; Janssen: Consultancy, Honoraria, Research Funding, Speakers Bureau; Sanofi: Consultancy, Honoraria, Research Funding, Speakers Bureau; Adaptive: Honoraria; MaaT Pharma: Current equity holder in publicly-traded company.

*signifies non-member of ASH