CHRONOS Study Reveals Low Survival Rates in Third-Line GI-aGvHD Following Ruxolitinib Failure

New real-world data from the multicenter, retrospective CHRONOS study highlight treatment outcomes with MaaT013 in patients with steroid- and ruxolitinib (Jakafi)-refractory acute graft-versus-host disease (aGvHD) with gastrointestinal (GI) involvement, according to findings published in Bone Marrow Transplantation and presented at the 2026 European Society for Blood and Marrow Transplantation (EBMT) Annual Congress.^1,2

Results showed that on day 28, the objective response rate (ORR) was 36% (95% CI, 24–49%), the GI-ORR was 37% (95% CI, 25–51%), and 29% (95% CI, 11–49%) of responders lost response within 30 days. Fifty-two percent of responders lost their response (95% CI, 29–72%) within 90 days.

Within the GI-ORR rate, the complete response rate was 22% (n = 13), 10% achieved very good partial response (VGPR; n = 6), and 5% of patients had a partial response (n = 3). The all-organ ORR at day 28 was similar at 36%.

Establishing a Contemporary Benchmark for Refractory aGvHD

In the CHRONOS study, investigators evaluated 59 adult patients across 16 European transplant centers who had failed both first-line corticosteroids and second-line ruxolitinib.

Most patients in the CHRONOS cohort presented with severe disease, including 46% with grade 3 and 48% with grade 4 aGvHD. Nearly all patients were steroid-resistant (97%) and ruxolitinib-resistant (95%).

In the absence of a standardized third-line therapy, clinicians utilized 12 different systemic interventions. The most frequent treatments included: anti-TNF-α (n = 20), extracorporeal photopheresis (n = 17), and vedolizumab (n = 10).

Waning Responses and Survival Limitations

By day 56, the GI-ORR dropped to 22%, and the all-organ ORR fell to 20%, suggesting that while initial stabilization may occur, responses to current third-line systemic therapies are often transient.

Additionally, the median real-world progression-free survival and median overall survival (OS) were both 86 days (95% CI: 54–128 days). Median OS was higher in responders than in non-responders (186 vs 45 days).

Contextualizing Microbiome-Based Therapy: The ARES Trial

The CHRONOS data were designed to provide real-world context for the ARES trial (NCT04769895), which evaluates MaaT013 (Xervyteg), a microbiome ecosystem therapy (MET).

MaaT013 is currently under regulatory review by the European Medicines Agency (EMA), with feedback anticipated in mid-2026.

Data from the single-arm ARES trial, also presented at the EBMT 2026 Annual Congress showed that the GI-ORR was 62% at day 28 compared with the 37% observed in CHRONOS. Furthermore, the 12-month OS in the ARES trial was 54% compared with the 29% benchmark established by the real-world systemic therapies in CHRONOS.

Clinical Implications for Oncology Nursing Practice

Acute GvHD with GI involvement is associated with life-threatening complications, including intestinal bleeding, profound diarrhea, and abdominal pain, which often lead to infection, malnutrition, and organ failure.

"CHRONOS provides a contemporary reference point for third-line GI-aGvHD, underscoring both the gravity of this condition and the persistent lack of standardized, effective therapies," Johannes Clausen, MD, the primary author of the publication, stated in a press release about the publication.

References

1. Clausen J, , Simón JAP, Carré M, et al. Clinical outcomes of third-line therapy for aGvHD with gastrointestinal involvement after steroids and ruxolitinib failure. Bone Marrow Transplant. Published online ahead of print March 28, 2026. doi:10.1038/s41409-026-02825-0
2. MaaT Pharma Announces Publication of Retrospective Data in Third-Line Acute GvHD from the CHRONOS Study in Bone Marrow Transplantation Journal. News release. BioSpace. Published April 1, 2026. https://www.biospace.com/press-releases/maat-pharma-announces-publication-of-retrospective-data-in-third-line-acute-gvhd-from-the-chronos-study-in-bone-marrow-transplantation-journal