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

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.

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Publication Details

Journal
Blood Advances
Published
2025-08-15
DOI
https://doi.org/10.1182/bloodadvances.2025017116
Citations
2
Primary Topic
Sepsis Diagnosis and Treatment
Type
article
Field-Weighted Citation Impact
2.71

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article

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

Ingrid Vášová, Timothy S. Olson, Joseph Portelli, James L.M. Ferrara et al.
2 citations
Blood Advances
Sepsis Diagnosis and Treatment
2.71
article

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

Ingrid Vášová, Timothy S. Olson, Joseph Portelli, James L.M. Ferrara, Evelyn Ullrich, Sigrun Gleich, Hannah Choe, Muna Qayed, Chantiya Chanswangphuwana, Nikolaos Katsivelos, Zachariah DeFilipp, John E. Levine, Steven Kowalyk, Aaron Etra, Pietro Merli, Paibel Aguayo‐Hiraldo, Nikolaos Spyrou, Gilbert Eng, Yu Akahoshi, Carrie L. Kitko, Daniela Weber, Sabrina Kraus, Ivan Pašić, Julia Marx, Matthias Wölfl, George Morales, Francis Ayuk, William J. Hogan, Robert Zeiser, Ran Reshef, Ryotaro Nakamura, Elizabeth Olson Hexner, Ioannis Louloudis, Rachel Young, Matthias Eder, Janna Baez
article en
2 citations

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.

Blood AdvancesVol. 9(22)
Goethe University Frankfurt (DE), University of Southern California (US), City Of Hope National Medical Center (US), Children's Hospital of Philadelphia (US), Children's Hospital of Los Angeles (US), Emory University (US), Chulalongkorn University (TH), Universität Hamburg (DE), University of Freiburg (DE), Friedrich-Alexander-Universität Erlangen-Nürnberg (DE), Columbia University Irving Medical Center (US), University Medical Center Freiburg (DE), Hospital for Sick Children (CA), King Chulalongkorn Memorial Hospital (TH), Princess Margaret Cancer Centre (CA), University Hospital Regensburg (DE), Medizinische Hochschule Hannover (DE), Massachusetts General Hospital (US), Universitätsklinikum Erlangen (DE), University Hospital Münster (DE), University Medical Center Hamburg-Eppendorf (DE), City of Hope (US), Aflac (United States) (US), Princess Margaret Hospital (NZ), Bambino Gesù Children's Hospital (IT), Universitätsklinikum Würzburg (DE), Mayo Clinic in Florida (US), Children's Healthcare of Atlanta (US), Comprehensive Cancer Center Erlangen (DE), Istituti di Ricovero e Cura a Carattere Scientifico (IT), The Ohio State University (US), University of Regensburg (DE), University of Pennsylvania (US), Vanderbilt University Medical Center (US), Icahn School of Medicine at Mount Sinai (US)
AstraZeneca, Alexion Pharmaceuticals, Medpace, José Carreras Leukämie-Stiftung, National Institutes of Health, Japan Society for the Promotion of Science, National Cancer Institute
Good health and well-being
Openalex Percentile: Top 9%
Sepsis Diagnosis and Treatment
2.71
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