Flares of acute graft-versus-host disease: a Mount Sinai Acute GVHD International Consortium analysis
Yu Akahoshi, Nikolaos Spyrou, Matthias Hoepting, Paibel Aguayo‐Hiraldo, Francis Ayuk, Chantiya Chanswangphuwana, Hannah Choe, Matthias Eder, Aaron Etra, Stephan A. Grupp, Elizabeth O. Hexner, William J. Hogan, Carrie L. Kitko, Sabrina Kraus, Monzr M. Al Malki, Pietro Merli, Muna Qayed, Ran Reshef, Tal Schechter‐Finkelstein, Evelyn Ullrich, Ingrid Vášová, Matthias Wölfl, Robert Zeiser, Janna Baez, Rahnuma Beheshti, Gilbert Eng, Sigrun Gleich, Stelios Kasikis, Nikolaos Katsivelos, Steven Kowalyk, George Morales, Rachel Young, Zachariah DeFilipp, James L.M. Ferrara, John E. Levine, Ryotaro Nakamura
Abstract
ABSTRACT: The absence of a standardized definition for graft-versus-host disease (GVHD) flares and data on its clinical course are significant concerns. We retrospectively evaluated 968 patients across 23 Mount Sinai Acute GVHD International Consortium (MAGIC) transplant centers who achieved complete response (CR) or very good partial response (VGPR) within 4 weeks of treatment. The cumulative incidence of flares within 6 months was 22%, and flares were associated with a higher risk of nonrelapse mortality (NRM; adjusted hazard ratio [aHR], 4.84; 95% confidence interval [CI], 3.19-7.36; P < .001). Flares were more severe (grades 3/4, 41% vs 16%; P < .001) and had more frequent lower gastrointestinal (LGI) involvement (55% vs 32%; P < .001) than the initial GVHD. At CR/VGPR, elevated MAGIC biomarkers predicted the future occurrence of a flare, along with its severity and LGI involvement. In multivariate analyses, higher Ann Arbor (AA) biomarker scores at CR/VGPR were significant risk factors for flares (AA2 vs AA1: aHR, 1.81 [95% CI, 1.32-2.48; P = .001]; AA3 vs AA1: aHR, 3.14 [95% CI, 1.98-4.98; P < .001]), as were early response to initial treatment (aHR, 1.84; 95% CI, 1.21-2.80; P = .004) and HLA-mismatched unrelated donor (aHR, 1.74; 95% CI, 1.00-3.02; P = .049). MAGIC biomarkers also stratified the risk of NRM both at CR/VGPR and at the time of flare. We conclude that GVHD flares are common and carry a significant mortality risk. The occurrence of future flares can be predicted by serum biomarkers that may serve to guide adjustment and discontinuation of immunosuppression.