Novel Microbiome Intervention Addresses Refractory Chronic GVHD

Amandeep Salhotra, MD, of City of Hope National Medical Center in Duarte, California, highlights a promising new approach for patients suffering from steroid and ruxolitinib-refractory chronic graft-versus-host disease (GVHD): a microbiome intervention known as MaaT013 (Xervyteg). This therapy is designed for patients with lower gastrointestinal (GI) GVHD, a population that often has very limited options when standard treatments fail. MaaT013 consists of a standardized mix of high-diversity bacteria collected from healthy donors. It is administered as an enema in three doses, following a pretreatment phase of oral vancomycin to prepare the gut environment.

The primary end point of the phase 3 ARES trial (NCT04769895) focused on the overall response rate at day 28. The results were striking, with patients achieving an overall response rate of nearly 62%. This is particularly significant given the difficult-to-treat nature of this refractory patient population. Longitudinal data further supports the efficacy of MaaT013; after 1 year of follow-up, almost 50% of the patients continued to maintain a clinical response. Those who initially responded to the microbiome intervention generally sustained that benefit over a period of 6 months to 1 year.

The success of this trial opens the door for a novel therapeutic category in the management of high-risk GVHD. By restoring the balance of the intestinal flora, MaaT013 addresses the underlying inflammatory environment of the gut in a way that traditional immunosuppressants cannot. Salhotra is optimistic that once this intervention receives formal approval, it will become an essential tool for treating patients with high-risk, refractory lower GI GVHD, significantly improving long-term clinical outcomes and quality of life.