The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease

Srinagesh HK, Özbek U, Kapoor U, Ayuk F, Aziz M, Ben-David K, Choe HK, DeFilipp Z, Etra A, Grupp SA, Hartwell MJ, Hexner EO, Hogan WJ, Karol AB, Kasikis S, Kitko CL, Kowalyk S, Lin JY, Major-Monfried H, Mielke S, Merli P, Morales G, Ordemann R, Pulsipher MA, Qayed M, Reddy P, Reshef R, Rösler W, Sandhu KS, Schechter T, Shah J, Sigel K, Weber D, Wölfl M, Wudhikarn K, Young R, Levine JE, Ferrara JL (2019)

Publication Type: Journal article

Publication year: 2019

Journal

Book Volume: 3

Pages Range: 4034-4042

Journal Issue: 23

DOI: 10.1182/bloodadvances.2019000791

Abstract

The Mount Sinai Acute GVHD International Consortium (MAGIC) algorithm probability (MAP), derived from 2 serum biomarkers, measures damage to crypts in the gastrointestinal tract during graft-versus-host disease (GVHD). We hypothesized that changes in MAP after treatment could validate it as a response biomarker. We prospectively collected serum samples and clinical stages of acute GVHD from 615 patients receiving hematopoietic cell transplantation in 20 centers at initiation of first-line systemic treatment and 4 weeks later. We computed MAPs and clinical responses and compared their abilities to predict 6-month nonrelapse mortality (NRM) in the validation cohort (n = 367). After 4 weeks of treatment, MAPs predicted NRM better than the change in clinical symptoms in all patients and identified 2 groups with significantly different NRM in both clinical responders (40% vs 12%, P < .0001) and nonresponders (65% vs 25%, P < .0001). MAPs successfully reclassified patients for NRM risk within every clinical grade of acute GVHD after 4 weeks of treatment. At the beginning of treatment, patients with a low MAP that rose above the threshold of 0.290 after 4 weeks of treatment had a significant increase in NRM, whereas patients with a high MAP at onset that fell below that threshold after treatment had a striking decrease in NRM that translated into clear differences in overall survival. We conclude that a MAP measured before and after treatment of acute GVHD is a response biomarker that predicts long-term outcomes more accurately than change in clinical symptoms. MAPs have the potential to guide therapy for acute GVHD and may function as a useful end point in clinical trials.

Authors with CRIS profile

Involved external institutions

Icahn School of Medicine at Mount Sinai United States (USA) (US) Universitätsklinikum Hamburg-Eppendorf (UKE) Germany (DE) Ohio State University United States (USA) (US) Massachusetts General Hospital United States (USA) (US) University of Pennsylvania (UPenn) United States (USA) (US) Mayo Clinic United States (USA) (US) Vanderbilt University United States (USA) (US) Universitätsklinikum Würzburg Germany (DE) Ospedale Pediatrico Bambino Gesu Italy (IT) Universitätsklinikum Carl Gustav Carus Dresden Germany (DE) Children's Hospital Los Angeles United States (USA) (US) Emory University United States (USA) (US) University of Michigan United States (USA) (US) Columbia University Irving Medical Center (CUIMC) United States (USA) (US) City of Hope Medical Center United States (USA) (US) The Hospital for Sick Children (SickKids) Canada (CA) Universität Regensburg Germany (DE) Chulalongkorn University / จุฬาลงกรณ์มหาวิทยาลัย Thailand (TH)

How to cite

APA:

Srinagesh, H.K., Özbek, U., Kapoor, U., Ayuk, F., Aziz, M., Ben-David, K.,... Ferrara, J.L. (2019). The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease. Blood Advances, 3(23), 4034-4042. https://doi.org/10.1182/bloodadvances.2019000791

MLA:

Srinagesh, Hrishikesh K., et al. "The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease." Blood Advances 3.23 (2019): 4034-4042.

BibTeX: Download