The MAGIC composite response: a novel end point integrating clinical and biomarker parameters for acute GVHD

Akahoshi Y, Portelli J, Katsivelos N, Louloudis IE, Aguayo-Hiraldo P, Ayuk F, Chanswangphuwana C, Choe HK, Eder M, Etra AM, Hexner EO, Kitko CL, Kraus S, Merli P, Olson TS, Pasic I, Qayed M, Reshef R, Schechter T, Marx J, Ullrich E, Vasova I, Weber D, Wölfl M, Zeiser R, Baez J, Eng G, Gleich S, Kowalyk S, Morales G, Spyrou N, Young R, DeFilipp Z, Hogan WJ, Nakamura R, Levine JE, Ferrara JL (2025)

Publication Type: Journal article

Publication year: 2025

Journal

Book Volume: 9

Pages Range: 5763-5773

Journal Issue: 22

DOI: 10.1182/bloodadvances.2025017116

Abstract

Changes in the clinical symptoms of acute graft-versus-host disease (GVHD) are currently used to assess treatment responses. The Mount Sinai Acute GVHD International Consortium (MAGIC) consortium has recently revealed that the integration of serum biomarkers with clinical symptoms at the onset of treatment in a MAGIC composite score (MCS) more accurately predicts treatment response and 6-month nonrelapse mortality (NRM) than clinical symptoms alone. In this study, we evaluated whether the integration of serum biomarkers and clinical symptoms on day 28 (D28) would also better predict NRM than clinical response only (CRO). We analyzed data from 1135 patients receiving systemic treatment for acute GVHD and created a fourth MCS category for patients with complete resolution of symptoms and low-risk clinical biomarkers on D28. Using a classification and regression tree model with 6-month NRM as the end point, we identified status of MCS 0 or MCS 1 at D28 as responses, which we termed the MAGIC composite response (MCR). In the validation cohort (n = 309), MCR more accurately predicted 6-month NRM than CRO (area under the curve: 0.77 vs 0.69; P = .014) and demonstrated higher negative and positive predictive values. MCR correctly reclassified both clinical nonresponders and responders: 28 of 213 clinical responders (13%) became nonresponders with fivefold higher NRM (34.3% vs 6.8%, P < .001) and a larger group (29/96, 30%) of clinical nonresponders became responders with sixfold lower NRM (7.6% vs 50.7%, P < .001). These findings support the use of MCR as a superior surrogate end point for long-term GVHD control and survival in future clinical trials.

Authors with CRIS profile

Involved external institutions

Icahn School of Medicine at Mount Sinai United States (USA) (US) Massachusetts General Hospital United States (USA) (US) Mayo Clinic United States (USA) (US) City of Hope Medical Center United States (USA) (US) Universitätsklinikum Würzburg Germany (DE) Universitätsklinikum Freiburg Germany (DE) Universität Regensburg Germany (DE) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) The Hospital for Sick Children (SickKids) Canada (CA) Universitätsklinikum Münster Germany (DE) Goethe-Universität Frankfurt am Main Germany (DE) University of Southern California (USC) United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย Thailand (TH) Ohio State University United States (USA) (US) Medizinische Hochschule Hannover (MHH) / Hannover Medical School Germany (DE) Penn Medicine United States (USA) (US) Vanderbilt University United States (USA) (US) Ospedale Pediatrico Bambino Gesu Italy (IT) Children's Hospital of Philadelphia United States (USA) (US) Princess Margaret Cancer Centre / Princess Margaret Hospital Canada (CA) Emory University United States (USA) (US)

How to cite

APA:

Akahoshi, Y., Portelli, J., Katsivelos, N., Louloudis, I.E., Aguayo-Hiraldo, P., Ayuk, F.,... Ferrara, J.L. (2025). The MAGIC composite response: a novel end point integrating clinical and biomarker parameters for acute GVHD. Blood Advances, 9(22), 5763-5773. https://doi.org/10.1182/bloodadvances.2025017116

MLA:

Akahoshi, Yu, et al. "The MAGIC composite response: a novel end point integrating clinical and biomarker parameters for acute GVHD." Blood Advances 9.22 (2025): 5763-5773.

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