“For patients who fail both steroids and ruxolitinib, there is a true unmet need – MAAT013 could change that”
At the 52nd Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT) in Madrid, Prof Florent Malard (Saint-Antoine Hospital, Sorbonne University, Paris, France) presented the final results of the pivotal phase III ARES trial evaluating microbiome therapy transfer MAAT013 in a challenging clinical setting: ruxolitinib-refractory acute graft-versus-host disease (GvHD) with gastrointestinal involvement. With few effective options and poor outcomes in this setting, the study highlights how this novel microbiome-based, immunomodulatory approach by restoring gut microbiome diversity to modulate the immune system could redefine third-line treatment.
The treatment landscape for acute GvHD is clearly defined in the early lines: steroids remain the standard first-line therapy, followed by ruxolitinib in the second-line setting. However, a substantial proportion of patients fail both. For these individuals – particularly those with gastrointestinal involvement, which represents the most severe form of the disease – there are no approved or truly effective options. Outcomes are extremely poor, and this represents a major unmet need. Increasingly, we understand that microbiome dysbiosis is closely linked to worse prognosis in GvHD, which provided a strong rationale to explore microbiome-based therapies such as MAAT013.
Traditionally, third-line approaches have relied on adding further immunosuppressive agents. While these can sometimes provide disease control, they come at the cost of significant toxicity, particularly infections, and overall outcomes remain disappointing. MAAT013 represents a fundamentally different strategy. It is not an immunosuppressive therapy but rather an immunomodulatory one, acting through restoration of microbiome balance. This distinction is important – it allows for disease control with potentially less toxicity, which likely contributes to the improved outcomes we are observing.
ARES was a pivotal phase III, non-randomized study. Given the absence of a standard of care in this refractory setting, a randomized design was not considered appropriate, as it could expose patients to ineffective or non-approved treatments. The study included patients with acute GvHD who had failed both steroids and ruxolitinib, with a focus on gastrointestinal involvement. The primary endpoint was the gastrointestinal overall response rate at day 28, which is a well-established endpoint in this context.
The results were very encouraging. The primary endpoint – gastrointestinal overall response rate at day 28 – was 62%, which is a strong signal in this population. Importantly, these responses were durable, being maintained at day 56 and at three months. Moreover, achieving a response translated into improved overall survival, which is ultimately what matters most for these patients.
These findings suggest that microbiome therapy with MAAT013 could become the new standard third-line treatment for patients who fail both steroids and ruxolitinib. While the primary focus was gastrointestinal disease, we also observed responses in other organ systems, including the skin and liver. This indicates that the therapy may have systemic immunomodulatory effects, rather than acting solely at the gut level.
The immediate priority is to secure regulatory approval so that this therapy can be made broadly available to patients in need. Beyond that, an important question is whether we can move this approach earlier in the treatment pathway – or even into the prophylactic setting. Preventing GvHD is always preferable to treating it. Ongoing phase III studies are exploring microbiome-based strategies in prophylaxis, and we hope these will provide definitive answers on how best to integrate this approach into clinical practice.
About the European Society for Blood and Marrow Transplantation (EBMT)
The EBMT is a community of healthcare professionals, involved in clinical haematopoietic cell transplantation and cellular therapy, who share their experiences and develop co-operative studies. The EBMT has a governing body called the Board of Association and three sets of groups that channel the society’s research aims and other activities: the EBMT Working Parties, Committees, and Nurses Group, which addresses issues within the field specifically related to nursing.
This content has been developed in collaboration with the European Society for Blood and Marrow Transplantation for touchHEMATOLOGY. Views expressed are the speaker’s own and do not necessarily reflect the views of Touch Medical Media.
Disclosures: Florent Malard has no actual or potential conflicts of interest in relation to this interview, or in connection with the (EFPIA) HCP Code.
Cite: Gut Instinct: MAAT013 offers new hope for ruxolitinib-refractory GvHD patients. touchHEMATOLOGY. 7th April 2026.
Interviewer: Caroline Markham
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