MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

Hannah Major-Monfried; Anne S. Renteria; Attaphol Pawarode; Pavan Reddy; Francis Ayuk; Ernst Holler; Yvonne A. Efebera; William J. Hogan; Matthias Wölfl; Muna Qayed; Elizabeth O. Hexner; Kitsada Wudhikarn; Rainer Ordemann; Rachel Young; Jay Shah; Matthew J. Hartwell; Mohammed S. Chaudhry; Mina Aziz; Aaron Etra; Gregory A. Yanik; Nicolaus Kröger; Daniela Weber; Yi Bin Chen; Ryotaro Nakamura; Wolf Rösler; Carrie L. Kitko; Andrew C. Harris; Michael Pulsipher; Ran Reshef; Steven Kowalyk; George Morales; Ivan Torres; Umut Özbek; James L.M. Ferrara; John E. Levine

doi:10.1182/blood-2018-01-822957

MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

Hannah Major-Monfried, Anne S. Renteria, Attaphol Pawarode, Pavan Reddy, Francis Ayuk, Ernst Holler, Yvonne A. Efebera, William J. Hogan, Matthias Wölfl, Muna Qayed, Elizabeth O. Hexner, Kitsada Wudhikarn, Rainer Ordemann, Rachel Young, Jay Shah, Matthew J. Hartwell, Mohammed S. Chaudhry, Mina Aziz, Aaron Etra, Gregory A. YanikNicolaus Kröger, Daniela Weber, Yi Bin Chen, Ryotaro Nakamura, Wolf Rösler, Carrie L. Kitko, Andrew C. Harris, Michael Pulsipher, Ran Reshef, Steven Kowalyk, George Morales, Ivan Torres, Umut Özbek, James L.M. Ferrara, John E. Levine

Hematology

Research output: Contribution to journal › Article › peer-review

57 Scopus citations

Abstract

Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n 5 236) and 2 validation cohorts separated in time (n 5 142 and n 5 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3a) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P 5 .004) and for Minnesota risk (0.72, P 5 .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies. (Blood.

Original language	English (US)
Pages (from-to)	2846-2855
Number of pages	10
Journal	Blood
Volume	131
Issue number	25
DOIs	https://doi.org/10.1182/blood-2018-01-822957
State	Published - Jun 21 2018

ASJC Scopus subject areas

Biochemistry
Immunology
Hematology
Cell Biology

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Major-Monfried, H., Renteria, A. S., Pawarode, A., Reddy, P., Ayuk, F., Holler, E., Efebera, Y. A., Hogan, W. J., Wölfl, M., Qayed, M., Hexner, E. O., Wudhikarn, K., Ordemann, R., Young, R., Shah, J., Hartwell, M. J., Chaudhry, M. S., Aziz, M., Etra, A., ... Levine, J. E. (2018). MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD. Blood, 131(25), 2846-2855. https://doi.org/10.1182/blood-2018-01-822957

Major-Monfried, H, Renteria, AS, Pawarode, A, Reddy, P, Ayuk, F, Holler, E, Efebera, YA, Hogan, WJ, Wölfl, M, Qayed, M, Hexner, EO, Wudhikarn, K, Ordemann, R, Young, R, Shah, J, Hartwell, MJ, Chaudhry, MS, Aziz, M, Etra, A, Yanik, GA, Kröger, N, Weber, D, Chen, YB, Nakamura, R, Rösler, W, Kitko, CL, Harris, AC, Pulsipher, M, Reshef, R, Kowalyk, S, Morales, G, Torres, I, Özbek, U, Ferrara, JLM & Levine, JE 2018, 'MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD', Blood, vol. 131, no. 25, pp. 2846-2855. https://doi.org/10.1182/blood-2018-01-822957

@article{b620c6b055ab445399927ef0bf39cdad,

title = "MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD",

abstract = "Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n 5 236) and 2 validation cohorts separated in time (n 5 142 and n 5 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3a) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P 5 .004) and for Minnesota risk (0.72, P 5 .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies. (Blood.",

author = "Hannah Major-Monfried and Renteria, {Anne S.} and Attaphol Pawarode and Pavan Reddy and Francis Ayuk and Ernst Holler and Efebera, {Yvonne A.} and Hogan, {William J.} and Matthias W{\"o}lfl and Muna Qayed and Hexner, {Elizabeth O.} and Kitsada Wudhikarn and Rainer Ordemann and Rachel Young and Jay Shah and Hartwell, {Matthew J.} and Chaudhry, {Mohammed S.} and Mina Aziz and Aaron Etra and Yanik, {Gregory A.} and Nicolaus Kr{\"o}ger and Daniela Weber and Chen, {Yi Bin} and Ryotaro Nakamura and Wolf R{\"o}sler and Kitko, {Carrie L.} and Harris, {Andrew C.} and Michael Pulsipher and Ran Reshef and Steven Kowalyk and George Morales and Ivan Torres and Umut {\"O}zbek and Ferrara, {James L.M.} and Levine, {John E.}",

note = "Publisher Copyright: {\textcopyright} 2018 by The American Society of Hematology.",

year = "2018",

month = jun,

day = "21",

doi = "10.1182/blood-2018-01-822957",

language = "English (US)",

volume = "131",

pages = "2846--2855",

journal = "Blood",

issn = "0006-4971",

publisher = "American Society of Hematology",

number = "25",

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TY - JOUR

T1 - MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

AU - Major-Monfried, Hannah

AU - Renteria, Anne S.

AU - Pawarode, Attaphol

AU - Reddy, Pavan

AU - Ayuk, Francis

AU - Holler, Ernst

AU - Efebera, Yvonne A.

AU - Hogan, William J.

AU - Wölfl, Matthias

AU - Qayed, Muna

AU - Hexner, Elizabeth O.

AU - Wudhikarn, Kitsada

AU - Ordemann, Rainer

AU - Young, Rachel

AU - Shah, Jay

AU - Hartwell, Matthew J.

AU - Chaudhry, Mohammed S.

AU - Aziz, Mina

AU - Etra, Aaron

AU - Yanik, Gregory A.

AU - Kröger, Nicolaus

AU - Weber, Daniela

AU - Chen, Yi Bin

AU - Nakamura, Ryotaro

AU - Rösler, Wolf

AU - Kitko, Carrie L.

AU - Harris, Andrew C.

AU - Pulsipher, Michael

AU - Reshef, Ran

AU - Kowalyk, Steven

AU - Morales, George

AU - Torres, Ivan

AU - Özbek, Umut

AU - Ferrara, James L.M.

AU - Levine, John E.

PY - 2018/6/21

Y1 - 2018/6/21

N2 - Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n 5 236) and 2 validation cohorts separated in time (n 5 142 and n 5 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3a) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P 5 .004) and for Minnesota risk (0.72, P 5 .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies. (Blood.

AB - Acute graft-versus-host disease (GVHD) is treated with systemic corticosteroid immunosuppression. Clinical response after 1 week of therapy often guides further treatment decisions, but long-term outcomes vary widely among centers, and more accurate predictive tests are urgently needed. We analyzed clinical data and blood samples taken 1 week after systemic treatment of GVHD from 507 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC), dividing them into a test cohort (n 5 236) and 2 validation cohorts separated in time (n 5 142 and n 5 129). Initial response to systemic steroids correlated with response at 4 weeks, 1-year nonrelapse mortality (NRM), and overall survival (OS). A previously validated algorithm of 2 MAGIC biomarkers (ST2 and REG3a) consistently separated steroid-resistant patients into 2 groups with dramatically different NRM and OS (P < .001 for all 3 cohorts). High biomarker probability, resistance to steroids, and GVHD severity (Minnesota risk) were all significant predictors of NRM in multivariate analysis. A direct comparison of receiver operating characteristic curves showed that the area under the curve for biomarker probability (0.82) was significantly greater than that for steroid response (0.68, P 5 .004) and for Minnesota risk (0.72, P 5 .005). In conclusion, MAGIC biomarker probabilities generated after 1 week of systemic treatment of GVHD predict long-term outcomes in steroid-resistant GVHD better than clinical criteria and should prove useful in developing better treatment strategies. (Blood.

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DO - 10.1182/blood-2018-01-822957

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AN - SCOPUS:85048708977

SN - 0006-4971

VL - 131

SP - 2846

EP - 2855

JO - Blood

JF - Blood

IS - 25

ER -

MAGIC biomarkers predict long-term outcomes for steroid-resistant acute GVHD

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