TOPLINE: 

Refined response (RR) criteria for acute graft-vs-host disease (GVHD) showed improved predictive performance over conventional criteria, with higher area under the curve (AUC) values and negative predictive values across multiple validation cohorts. Classification of persistent mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses drove the improvements.

METHODOLOGY:

• Researchers analyzed data from > 300 Japanese transplant centers through the Japanese Society for Transplantation and Cellular Therapy (JSTCT) and 24 centers across North America, Europe, and Thailand through the Mount Sinai Acute GVHD International Consortium (MAGIC).
• Analysis included adolescent/adult patients aged > 16 years who underwent their first allogeneic hematopoietic cell transplantation between 2014-2021 in Japan and 2014-2022 in MAGIC centers.
• Participants who received systemic corticosteroids as primary treatment for grade 2-4 acute GVHD were included in the primary treatment cohort, while those who received second-line treatment formed the second-line treatment cohort.

TAKEAWAY:

• Day 28 RR demonstrated higher area under the receiver operating characteristic curve than overall response in both JSTCT (AUC, 0.73 vs 0.69; P < .001) and MAGIC (AUC, 0.71 vs 0.68; P = .032) validation sets.
• Patients with partial response by conventional criteria but nonresponse by refined criteria experienced significantly higher nonrelapse mortality, with > 80% having persistent gastrointestinal GVHD at day 28.
• After second-line treatment, RR showed substantially higher negative predictive values than overall response in both JSTCT (74.5% vs 66.0%; P < .001) and MAGIC (86.8% vs 76.1%; P = .004) cohorts. 

IN PRACTICE:

"Classifying persistent but mild skin symptoms as responses and residual lower gastrointestinal GVHD as nonresponses were major drivers in improving the prognostic performance of RR. Our externally validated day 28 RR would serve as a better end point than conventional criteria in future first- and second-line treatment trials," the authors of the study wrote.

SOURCE:

The study was led by Yu Akahoshi, Division of Hematology/Medical Oncology at The Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai in New York. It was published online in Blood Advances.

LIMITATIONS: 

According to the authors, using GVHD grades instead of target organ stages for categorizing patients was necessary to avoid unreliable results from small patient groups. Upper gastrointestinal staging data was not available in the JSTCT dataset used to develop day 28 RR criteria. Ruxolitinib had not yet been approved for acute GVHD in Japan during the study period, limiting validation of the RR criteria after second-line treatment with ruxolitinib to only the MAGIC dataset. Additionally, more direct measures of long-term GVHD control such as GVHD flare incidence were not available, and GVHD biomarkers that could serve as response biomarkers and predict flares and nonrelapse mortality were not included in the analysis. 

DISCLOSURES:

This study received support from the Japanese government subsidy of Act on the Promotion of Appropriate Provision of Hematopoietic Stem Cells for Transplantation and grants from the US National Institutes of Health/National Cancer Institute, the Pediatric Cancer Foundation, and the German Jose Carreras Leukemia Foundation. Yu Akahoshi reported receiving honoraria from Novartis and AstraZeneca. Additional disclosures are noted in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.