The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
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The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease. / Srinagesh, Hrishikesh K; Özbek, Umut; Kapoor, Urvi; Ayuk, Francis; Aziz, Mina; Ben-David, Kaitlyn; Choe, Hannah K; DeFilipp, Zachariah; Etra, Aaron; Grupp, Stephan A; Hartwell, Matthew J; Hexner, Elizabeth O; Hogan, William J; Karol, Alexander B; Kasikis, Stelios; Kitko, Carrie L; Kowalyk, Steven; Lin, Jung-Yi; Major-Monfried, Hannah; Mielke, Stephan; Merli, Pietro; Morales, George; Ordemann, Rainer; Pulsipher, Michael A; Qayed, Muna; Reddy, Pavan; Reshef, Ran; Rösler, Wolf; Sandhu, Karamjeet S; Schechter, Tal; Shah, Jay; Sigel, Keith; Weber, Daniela; Wölfl, Matthias; Wudhikarn, Kitsada; Young, Rachel; Levine, John E; Ferrara, James L M.
in: Blood Adv, Jahrgang 3, Nr. 23, 10.12.2019, S. 4034-4042.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The MAGIC algorithm probability is a validated response biomarker of treatment of acute graft-versus-host disease
AU - Srinagesh, Hrishikesh K
AU - Özbek, Umut
AU - Kapoor, Urvi
AU - Ayuk, Francis
AU - Aziz, Mina
AU - Ben-David, Kaitlyn
AU - Choe, Hannah K
AU - DeFilipp, Zachariah
AU - Etra, Aaron
AU - Grupp, Stephan A
AU - Hartwell, Matthew J
AU - Hexner, Elizabeth O
AU - Hogan, William J
AU - Karol, Alexander B
AU - Kasikis, Stelios
AU - Kitko, Carrie L
AU - Kowalyk, Steven
AU - Lin, Jung-Yi
AU - Major-Monfried, Hannah
AU - Mielke, Stephan
AU - Merli, Pietro
AU - Morales, George
AU - Ordemann, Rainer
AU - Pulsipher, Michael A
AU - Qayed, Muna
AU - Reddy, Pavan
AU - Reshef, Ran
AU - Rösler, Wolf
AU - Sandhu, Karamjeet S
AU - Schechter, Tal
AU - Shah, Jay
AU - Sigel, Keith
AU - Weber, Daniela
AU - Wölfl, Matthias
AU - Wudhikarn, Kitsada
AU - Young, Rachel
AU - Levine, John E
AU - Ferrara, James L M
N1 - © 2019 by The American Society of Hematology.
PY - 2019/12/10
Y1 - 2019/12/10
N2 - 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.
AB - 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.
U2 - 10.1182/bloodadvances.2019000791
DO - 10.1182/bloodadvances.2019000791
M3 - SCORING: Journal article
C2 - 31816061
VL - 3
SP - 4034
EP - 4042
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 23
ER -