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, 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
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 = 236) and 2 validation cohorts separated in time (n = 142 and n = 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 REG3α) 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 = .004) and for Minnesota risk (0.72, P = .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.
Conflict of interest statement
Conflict-of-interest disclosure: J.E.L., J.L.M.F., and U.Ö. are joint inventors on a GVHD biomarker patent. The remaining authors declare no competing financial interests.
© 2018 by The American Society of Hematology.
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Source: PubMed