CT-198 Pooled Fecal Allogeneic Microbiotherapy for Refractory Gastrointestinal Acute Graft-Versus-Host Disease: Results from the Early Access Program in Europe

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IntroductionWe report clinical outcomes from 140 steroid-refractory (SR) or steroid-dependent (SD) GI-aGvHD patients treated with the pooled allogeneic microbiotherapy MaaT013 as part of the Early Access Program (EAP) in Europe.Patients and MethodsThe 140 patients with SR/SD GI-aGvHD, who had been treated unsuccessfully with 1 to 6 systemic lines, received MaaT013 therapy. For each patient, a total of 3 MaaT013 administrations were planned every 7 ± 2 days.ResultsThe GI objective response rate (GI-ORR) on day 28 (D28) was 52%: 39 complete responses (CR, 28%), 26 very good partial responses (19%), 8 partial responses (PR, 6%). OS was 54% at month 6 (M6), 47% at M12, and 42% at M18. OS was significantly higher in patients achieving at least GIPR at D28 (Responder, R; n=73) than in patients with treatment failure (Non-responder, NR; n=67): 74% versus 33% at M6, 68% versus 24% at M12, 58% versus 24% at M18 (P<.0001). GI-ORR was higher in 49 patients previously treated with ruxolitinib (2nd line) and MaaT013 (3rd line): 63% at D28, with 49% CR. OS was 52% at M6, 49% at M12, and 42% at M18. OS was significantly higher in R patients than in NR patients (M6, 76% versus 11%; M12, 76% versus 6%, M18, 64% versus 6% for R and NR respectively, P<.0001). MaaT013 displayed a good overall safety profile: 22 pharmacovigilance cases were considered possibly related to MaaT013 by either the physician or the company: sepsis in 6, bacteremia in 10, rectal bleeding in 3, Clostridioides difficile colitis in 1, Escherichia coli osteoarthritis in 1, Geotrichum silvicola in stools in 1. No pathogen transmission was reported. In 2 patients, non-pathogenic commensal bacteria isolated following infectious events were detected in the administered MaaT013. Causality could not be formally excluded in these cases. No death was related to MaaT013 administration.ConclusionEAP clinical data showed that MaaT013 was safe and effective for the treatment of SR/SD-GI-aGvHD, especially after ruxolitinib failure. GI response correlated with increased OS, suggesting a favorable benefit-risk profile for MaaT013. A Phase 3 trial is currently ongoing to confirm these results in ruxolitinib-refractory patients (NCT04769895).

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