A 2025 update from the Working Groups of NIH Chronic GvHD Consensus Conference

The third NIH Consensus Development Project on Criteria for GvHD Clinical Trials was convened in 2020 to make recommendations for improving the management of cGvHD. An interim meeting was held in October 2024 to review the 2020 recommendations. During the meeting, four NIH Consensus Working Groups (WGs) presented progress in their respective areas. The summary of the WGs reports and recommendations was published recently by Lee et al. in Transplantation and Cellular Therapy.¹

The four WGs included: WG 1: Etiology and prevention; WG 2a: Clinical implementation and diagnosis; WG 2b: Preemptive therapy; WG 3: Treatment; and WG 4: Highly morbid forms. An additional taskforce on atypical cGvHD also reported progress in their area.

Key learnings

WG 1 highlights major progress in cGvHD prevention, as demonstrated through PTCy trials in the context of RIC. Ongoing studies are evaluating lower doses of PTCy or PTCy in combination with other agents for GvHD prophylaxis, while reducing toxicities.

WG 2a emphasizes the need for successful implementation of community-based approaches for early cGvHD identification and diagnosis. Future studies should compare cGvHD staging before and after educational interventions and focus on early interventions to prevent long-term morbidity. 

WG 2b underlined that identified biomarkers have inadequate PPV or NPV to guide preemptive trials. Given the heterogeneous nature of cGvHD, it is essential to identify subclinical indicators of common pathways in blood or focus on tissue instead of blood. 

The HSCT community needs to be more efficient in addressing unmet clinical needs and gaps in cGvHD pathophysiology, according to WG3. Additionally, they advise the development of alternative trial designs and use of common control groups for comparison with novel agents.

According to WG 4, the approval of novel agents for more advanced forms of cGvHD indicates progress. However, the ability to evaluate treatment benefits is limited by a lack of measures for signaling highly morbid forms such as advanced pulmonary cGvHD. 

Clinicians should be educated on the manifestations and challenges of diagnosing atypical cGvHD, according to the Atypical GvHD Taskforce. Furthermore, treatment guidelines are required for atypical cGvHD therapeutic approaches, which are different from those for classic GvHD.