The Congress Connection: cGvHD and Transplant Key Takeaways in 2025

Efficacy and safety of belumosudil as compared with best available therapy for the treatment of chronic graft-versus-host disease in the US population
Waller EK (USA)

The ROCKreal study demonstrated that BEL is an effective option for improving outcomes over BAT in patients with cGvHD, showing superior efficacy with higher ORR at 6 months and FFS at 1 year, and a favorable safety profile in real-world settings, consistent with the ROCKstar trial.

• This non-interventional study compared the efficacy and safety of BEL vs BAT for treating cGvHD in patients aged ≥12 years who had failed 2–5 prior LOTs. Data from 196 patients across 8 US sites were collected between March 1, 2015 and March 27, 2024.
• The ROCKreal study was designed to emulate a phase 3 RCT using causal inference methodology. Targeted maximum likelihood estimation was used to adjust for biases and correlations among multiple LOTs from the same patient.
• Efficacy and safety findings
  • 6-month ORR: BEL 38.7% (95% CI: 27.1–50.4) vs. BAT 26.8% (95% CI: 20.3–33.4); 44.2% improvement in ORR with BEL (p = 0.031).
  • 1-year FFS: BEL 61.2% vs. BAT 47.8%; 13.5% improvement in adjusted FFS at 1 year when treated with BEL (p = 0.032).
  • BEL had a lower AE rate per 100 LOT-years (41.19%) vs. BAT (51.32%).

Clinically meaningful improvement of modified Lee symptom scale in patients treated with belumosudil for steroid-refractory chronic GvHD: Evidence from real-world outcomes
Kim D (Canada)

RWE on symptom burden improvement in sR-cGvHD patients treated with BEL is limited, highlighting the need to assess PROs.

• This retrospective study evaluated treatment outcomes and mLSS in 36 patients with sR-cGvHD who received BEL under a managed access program in Canada (Mar 2023–Nov 2024). Treatment outcomes included ORR at 3/6 months, best ORR, and FFS. Clinically meaningful improvements in mLSS were assessed.
• Most patients were heavily pre-treated (median 5 prior lines), with severe cGvHD (69%). ORRs at 3 and 6 months were 55.0% and 69%, respectively, with a 6-month FFS of 71.9%. The mean mLSS decreased by 7.8 points within 6 months (28.7±2.4 to 20.9±4.2) after BEL treatment started and continued improving at 9 and 12 months. The most improved symptom domains were muscle/joints (54%), skin (46%), and eye/mouth (46%). No significant differences were observed between BEL/RUX and other treatments in ORR (64% vs 73%) or clinically meaningful improvements in mLSS (10.1 vs 8.6 points). Prior ECP treatment improved muscle/joint symptoms from 3 months without objective response.
• mLSS effectively captured early clinical improvements, supporting its role in symptom monitoring before NIH-defined objective responses.

Efficacy and safety of belumosudil for treatment of cGvHD: multicenter retrospective analysis of the French cohort of the compassionate use program
Loschi M (France)

The findings of this real-world study corroborated the ROCKstar trial outcomes, even with heavily pretreated patients, and did not identify any new adverse signals.

• This study analyzed 68 patients with cGvHD across French HCT centers who received BEL under a compassionate use program between April 2022 and September 2024.
• Most patients (66%) received BEL 200 mg BID, with a median follow up of 46 months. First-line therapy included corticosteroids (51%) or combination with other drugs (34%), mainly CNIs/ECP. Before BEL, patients received a median of 3 LOTs (range, 2–9), with 95.5% receiving ruxolitinib at any LOT.
• The best ORR was 57.3% (PR, 42.6%; CR, 14.7%); ORR at 3 months was 47% (PR, 42.6%; CR, 4.4%) and at 6 months was 45.6% (PR, 35.3%; CR, 10.3%). Liver and mouth cGvHD had the highest ORRs (72.7% and 70.4%, respectively). FFS at 6 and 12 months was 89.1% and 80.4%, respectively. OS at 6, 12, and 48 months was 97.1%, 95.6%, and 90.6%, respectively.

Exploring the impact of chronic graft-versus-host disease on the health-related quality of life of patients and caregivers: a qualitative survey-based study in France
Kiprijanovski D (France)

This study underscores the profound impact of cGvHD on the HrQoL of patients and caregivers, highlighting the need for improved treatments and multidisciplinary care.

• Conducted 22 interviews (17 patients, 5 caregivers) across France, focusing on experiences and needs related to cGvHD. Patients received ≥2 systemic treatments and had a cGvHD diagnosis for over 12 months.
• Patients and caregivers experience substantial physical, emotional, and psychological burdens, with cGvHD symptoms often perceived as a "price to pay" for surviving the original disease. Patients distinguish cGvHD symptoms from treatment side effects but experience both concurrently.
• Despite commendable expertise from haematologists, organ specialists often lack cGvHD knowledge, leading to ineffective treatments and strained patient-physician relationships. Patients and caregivers call for enhanced treatment efficacy and tolerability, improved physician training, psychological support, increased public awareness, and access to specialized care beyond haematology.

Impact of belumosudil treatment in advanced chronic graft-versus-host disease (cGvHD): insights into response-based T- and B-cell subpopulation dynamics
Ponce D (USA)

BEL treatment in advanced cGvHD shows promising immune modulation, with distinct shifts in T- and B-cell subpopulations among responders.

• This study evaluated 35 patients with steroid-refractory cGvHD treated with BEL from August 2021 to December 2022. Blood samples were collected at baseline, 6, and 12 months. Treatment response was defined as responders or nonresponders at 6 months.
• Immune Dynamics: Responders (n=20) exhibited higher baseline levels of activated T and B cells, including CD8+CTLA4+, CD8+HLA-DR+, CD19+CD27low, and CD19+CD24highCD38high. During therapy, both cohorts showed dynamic immune changes, with increases in CD4+TEM and CD8+TIM3+ cells. Responders demonstrated more favorable shifts, including a decrease in CD4+ naïve T cells and recent thymic emigrants, and a significant increase in B cells at 6 and 12 months (p = 0.026 and 0.018, respectively).
• BEL preserves immune function and induces beneficial immune changes in responders. Baseline immune profiles may help predict treatment response, warranting further studies with larger cohorts.

Description of patients and management of cGvHD in France based on natural language processing (NLP) from medical documents available in hospital electronic medical files
Kiprijanovski D (France)

In Europe, there is no standard therapeutic strategy for cGvHD in patients post allo-HSCT who fail second systemic LOT. This innovative approach uses AI-NLP to provide an insight into realworld cGvHD management in France.

• A cohort of allo-HSCT patients, with cGVHD and at least 12 months of follow-up was identified based on ADS using AINLP to structure data. The NLP derived data accuracy and completeness were validated through a three-step quality check: clinical research associate review, comparison with the European Bone Marrow Transplant registry, and expert validation.
• Out of 306 patients, 20 met the eligibility criteria, 60% of whom were males. Common reasons for allo-HSCT included acute myeloid leukemia (50.0%), and non-Hodgkin's lymphoma (27.8%). Median time to cGvHD was 128 days. Seven patients received at least 3 LOTs at the time of analysis.
• This novel AI-NLP approach efficiently identified and structured cGvHD patient data from medical records providing an insight into real-world cGvHD management in France. Eight hospitals and 220 patients are participating in this project, with ongoing analyses to validate the AI-NLP tool and describe treatments.

Living with GvHD - impact and experience
Barata A (USA)

Living with aGvHD and cGvHD significantly impacts patients' QoL, both physically and psychologically, necessitating comprehensive supportive care and interventions.

• Patients with aGvHD experience worsening symptoms such as insomnia (36%), nausea (21%), bowel trouble (32%), and pain (23%), within the first 2 weeks of hospitalization. These symptoms lead to psychological distress, including anxiety and depression, and increase the risk of PTSD, resulting in decreased QoL.¹
• cGvHD results in substantial impairments in physical functioning, social roles, and mental health, comparable to those seen in autoimmune diseases. Severity of cGvHD correlates with greater QoL impairments. Patients with severe cGvHD reported the lowest scores in all domains examined, including PCS and MCS of the SF-36 survey. cGvHD survivors face ongoing challenges, including late effects such as cognitive impairments, increased risk of recurrence and new cancers, and chronic conditions.^2,3
• Effective management of aGvHD and cGvHD includes routine screening for psychological distress, integrating PROs, maximizing care for the treatment of organ-specific aGvHD, optimizing nutrition, physical therapy and rehabilitation, access to psycho-oncology and mental health clinicians, and involvement of palliative care to address complex symptoms and improve overall well-being.^4,5

Incidence of graft versus host disease according to prophylaxis strategy in matched related and unrelated donor allogeneic hematopoietic stem cell transplantation: realworld experience of GETH-TC
Bento L (Spain)

In this real-world setting, PTCy, the most frequently used prophylaxis regimen, demonstrated superior effectiveness in reducing aGvHD and cGvHD incidence compared to traditional strategies in HLA-matched donor allo-HSCT, and should be recommended for GvHD prophylaxis, though further prospective studies are warranted.

• This retrospective study analyzed 859 allo-HSCT procedures (MSD, 447; MUD, 412) across 13 Spanish centers (2018–2020), assessing the incidence and severity of aGvHD and cGvHD using different prophylaxis strategies: PTCy, CNI + MTX, sirolimus, and ATG.
• The 3-year OS and PFS were 66% (95% CI 63–69) and 57% (95% CI 54–60), respectively, with a 1-year NRM of 14% (95% CI 12–16).
• The 6-month cumulative incidence of grade 2-4 aGvHD was 19% (95% CI 15.3–22.2) and grade 3-4 aGvHD was 6% (95% CI 3.7–7.8), with lower incidence of grade 2-4 aGvHD observed with PTCy compared to CNI + MTX and sirolimus-based prophylaxis. The 2-year cumulative incidence of moderate-severe cGvHD was 25% (95% CI 20.7–28.7), with lower incidence in PTCy compared to CNI + MTX in MUD transplants.

Challenges and opportunities of biomarkers in GvHD
Greinix HT (Austria)

While many promising biomarkers have been identified and validated, challenges remain in standardization, comparative study designs, and translation into routine clinical practice. Future focus lies in multi-center validation, early detection, risk-adapted therapy, and combining biomarkers with clinical scoring to improve patient outcomes in GvHD.

• The NIH consensus group definitions for biomarkers for either cGvHD or aGvHD is as follows: diagnostic, predictive, response and prognostic categorised as cellular, mediator, antibody types.⁶
• aGvHD: REG3α and ST2 indicate GI tissue damage. Both the biomarkers identified patients with a significant 6- month NRM of 28% in the high-risk group and 7% in the low-risk group. GvHD related mortality was also significant with the risk-score: 18% vs. 4%, p < 0.001, and is GI GvHD related: 17% vs. 8%, p < 0.001.7 Urinary proteomic profile aGvHD_MS17 is also available.⁸
• cGvHD: CXCL10, BAFF, IL-15, CD163, DKK3, ST2+CXCL9+MMP3+OPN (as a panel) are few promising biomarkers but yet to be confirmed in studies with test and verification cohorts.

Grade your GvHD yourself - development of an app to document chronic graft-versus-host disease by patients and caregivers
Denk A (Germany)

The development of the cGvHD app enables continuous and remote documentation of cGVHD symptoms by patients and caregivers, improving early detection and management.

• An app was developed to incorporate existing PROMs (LSS, NIH cGvHD self-assessment, and toxicity-related PROMs) for tracking cGvHD symptoms and toxicity over time. It enabled 24/7 symptom documentation, requiring at least weekly entries with bi-weekly reminders for 2 years.
• This adaptive design preselected questions based on previous responses. Data were automatically transferred to the German- Austrian-Swiss GvHD registry, allowing comparison of patientreported symptoms with physician assessments and paperbased PROMs from outpatient visits.
• Pilot testing of the cGvHD app was completed with 10 patients during routine follow-up after allo-HSCT, confirming feasibility with only 1 minor adjustment needed. The app demonstrated sufficient content validity, with no relevant symptoms missed compared to paper-based PROMs. Patients emphasized the need for weekly reminders and access to app results during clinic visits for symptom discussions. A shortcut function to report no symptoms was requested. Symptom severity was categorized into four grades across seven domains. The app aligned with paperbased PROMs in 67% of assessments (28/42), with only one severity-grade difference in the remaining cases.