From March 30 to April 2, the 51st Annual Meeting of the European Society for Blood and Marrow Transplantation (EBMT 2025) was held in Florence, Italy—the cradle of the Renaissance. As one of the most influential global events in hematology, this year's congress brought together more than 5,000 experts and scholars to explore cutting-edge advances in hematopoietic stem cell transplantation and cellular therapy.Among the most closely watched fields was graft-versus-host disease (GVHD), with several high-impact studies presented or updated during the meeting. For this special edition of Hematology Frontier, we invited Professor Qingxiao Song from the Xinqiao Hospital of Army Medical University to provide expert commentary on two landmark studies—one offering a breakthrough therapeutic approach for steroid-refractory gastrointestinal acute GVHD (SR-GI-aGVHD), and another introducing a promising new option for chronic GVHD (cGVHD). Don't miss these highlights.Prof. Qingxiao Song: At EBMT 2025, Professor Robert Zeiser from the University of Freiburg presented results from the STARGAZE trial—a multicenter, prospective Phase II study that, for the first time, evaluated the efficacy and safety of a GLP-2 analog (Apraglutide) combined with ruxolitinib in the treatment of steroid-refractory gastrointestinal acute GVHD (SR-GI-aGVHD). The trial stands out for both its innovative therapeutic mechanism and clinical relevance.
Mechanistically, the study builds on the team’s preclinical findings published in Blood in 2020, which showed a significant reduction in intestinal GLP-2 levels during acute GVHD. GLP-2 analogs offer a non-immunosuppressive regenerative strategy by repairing intestinal stem cells and Paneth cells, addressing the limitations of current therapies like ruxolitinib that target only immune modulation.
The clinical data from STARGAZE indicate that GLP-2 analogs are well tolerated, with most adverse events deemed unrelated to treatment. Across the study timeline, the overall response rates (ORR) in all organs were 58.1%, 51.6%, and 45.2% at Days 28, 56, and 91, respectively, while complete response (CR) rates ranged from 25.8% to 29.0%. These results support the efficacy and safety of combining Apraglutide with ruxolitinib in SR-GI-aGVHD.
Globally, other regenerative approaches are being explored to promote the repair of intestinal epithelial cells—including stem cells, Paneth cells, and goblet cells. For example, IL-22, reported by Dr. Alan Hanash at Memorial Sloan Kettering; the Wnt agonist R-Spondin1, studied by Professor Teshima in Japan; and IL-25 have all shown potential. These studies reflect a shared goal of intestinal regeneration in GVHD, not merely immunosuppression.
In China, SR-GI-aGVHD remains a therapeutic challenge due to limited second-line options and the high risk of infections from traditional immunosuppressants. The synergistic action of Apraglutide and ruxolitinib—combining immune modulation with intestinal regeneration—may reduce the risk of infection, making it particularly suitable for elderly or infection-prone patients. This research provides a promising new direction for combination therapy in such high-risk populations.
The STARGAZE study’s regenerative medicine concept is highly valuable and deserves attention from domestic research teams. However, the trial’s limitation lies in its small sample size (31 patients), and broader validation especially in Asian populations—is still needed.
In conclusion, the STARGAZE study offers a breakthrough approach to SR-GI-aGVHD, shifting the paradigm from suppression to repair. This concept holds great promise for clinical practice in China. Moving forward, international collaboration and locally-driven research will be crucial to developing personalized, China-specific strategies that better serve our patients.
Prof. Qingxiao Song: Chronic graft-versus-host disease (cGVHD) is a common and serious complication following hematopoietic stem cell transplantation. Up to 50% of patients may experience limited efficacy and significant toxicity from first-line corticosteroid therapy. While drugs such as ruxolitinib have been approved in recent years, a substantial unmet need remains for patients with refractory disease.
At the 2025 EBMT Congress, Professor Edmund K. Waller from the Winship Cancer Institute of Emory University shared the results of the ROCKreal study, which further supports the clinical value of the ROCK2 inhibitor belumosudil. This real-world study compared the efficacy of belumosudil versus best available therapy (BAT).
The data were compelling. The belumosudil group achieved a 6-month overall response rate (ORR) of 38.7%, compared with 26.8% in the BAT group. This represents an absolute improvement of 11.9% and a relative improvement of 44%, with statistical significance (P = 0.040). One-year failure-free survival (FFS) improved by 13.5% in the belumosudil group, with a median FFS extension of 2.8 months and a significantly reduced risk of treatment failure (P = 0.032). Although both groups experienced adverse events, the incidence of serious adverse events was lower in the belumosudil group (58% vs. 46%), and only 2% of belumosudil-treated patients experienced life-threatening events, compared with 16% in the BAT group.
It is worth noting that the median age of the study population was over 60 years, and most patients had failed multiple prior treatments, with a median of three organs affected—making this study population highly representative of elderly, refractory cGVHD patients commonly seen in Chinese clinical practice.
China has also conducted several studies on belumosudil. In the first multicenter Phase II study conducted in China, 30 patients were enrolled, two-thirds of whom had severe cGVHD. More than half had involvement of at least four organs. The ORR reached 73.3%, with a median time to response of just 4.3 weeks. A total of 56.7% of patients were able to reduce their steroid dose, and 27.3% discontinued steroids completely. The drug showed particularly strong efficacy in patients with oral (54.5%) and joint/fascia (77.8%) involvement. However, pneumonia occurred in 16.7% of patients, which should be monitored closely.
Another real-world Chinese study, presented at ASH 2024, included 20 patients with ultra-refractory disease (median of four prior therapies, 90% with four or more organs involved). In this challenging population, ORR was still as high as 90%. The median time to response was 1.6 months, and 80% of patients showed significant symptom improvement within 3 months. Notably, among patients who had failed ruxolitinib, the combination with belumosudil still resulted in an ORR of 86.7%. The incidence of grade ≥3 adverse events was only 10%, with infections being the most common.
These findings together suggest that belumosudil offers a new option for patients who have failed multiple lines of therapy. Chinese data, in particular, highlight its value in highly refractory populations. Combination strategies, such as belumosudil with ruxolitinib, may represent a promising therapeutic direction. This is further supported by recent Chinese data published in Blood on the dual JAK/ROCK inhibitor Rovadicitinib. Both U.S. and Chinese studies confirm that belumosudil, through its unique mechanism, provides a meaningful advancement in cGVHD treatment.
We look forward to more real-world data to guide precise clinical decision-making and further refine individualized strategies for Chinese patients.
References
[1] Robert Zeiser, et al. Safety and efficacy of the glucagon-like peptide 2 analog apraglutide in combination with ruxolitinib in steroid-refractory gastrointestinal acute graft-versus-host disease: the phase 2 STARGAZE trial. EBMT 2025: OS11-02.
[2] Ara T, Hashimoto D, Hayase E, et al. Intestinal goblet cells protect against GVHD after allogeneic stem cell transplantation via Lypd8. Sci Transl Med. 2020 Jul 1;12(550):eaaw0720. doi: 10.1126/scitranslmed.aaw0720. PMID: 32611682.
[3] Takashima S, Kadowaki M, Aoyama K, et al. The Wnt agonist R-spondin1 regulates systemic graft-versus-host disease by protecting intestinal stem cells. J Exp Med. 2011 Feb 14;208(2):285–294.
[4] Edmund K. Waller, et al. Efficacy and safety of belumosudil as compared with best available therapy for the treatment of chronic graft versus host disease in the U.S. population. EBMT 2025: OS11-03.
[5] Wang Y, Wu D, Zhang X, et al. A phase II study of belumosudil for chronic graft-versus-host disease in patients who failed at least one line of systemic therapy in China. BMC Med. 2024 Mar 26;22(1):142. doi: 10.1186/s12916-024-03348-5. PMID: 38532458; PMCID: PMC10964632.
[6] Wang Z, et al. Effectiveness and Safety of Belumosudil in Heavily-Treated Severe Chronic Graft-Versus-Host Disease (cGVHD) after Allogeneic Hematopoietic Stem Cell Transplant (allo-HSCT): A Real-World Observational Study. Blood. 2024;144 (Suppl 1): 7332.
[7] Zhao Y, Luo Y, Shi J, et al. A First-in-Class JAK/ROCK Inhibitor, Rovadicitinib, for Glucocorticoid-Refractory or -Dependent Chronic GVHD. Blood. 2025 Feb 26. doi: 10.1182/blood.2024026581. Epub ahead of print. PMID: 40009501.
Professor Qingxiao Song
Blood Diseases Center, Xinqiao Hospital, Second Affiliated Hospital of Army Medical University
- Member, Hematology Physician Committee, Chongqing Medical Association
- Member, American Society of Hematology (ASH)
- Editorial Board Member, Blood & Genomics
Professor Song’s research focuses on the basic and translational studies of hematopoietic stem cell regeneration, supported by the “Innovation Talent Base Program” under Chongqing’s Strategic Talent Initiative.
She leads several major research projects, including those funded by the National Natural Science Foundation for Young Scientists, Chongqing Innovation Consortium Program, and a Key Joint Project by Chongqing Health Commission.
Her research results have been published in internationally recognized journals such as Blood, Journal of Clinical Investigation, Nature Communications, PNAS, and American Journal of Transplantation, among others. She has authored 7 first-author papers and 2 corresponding-author papers.
