The MAGIC algorithm probability predicts treatment response and long-term outcomes to second-line therapy for acute GVHD
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The MAGIC algorithm probability predicts treatment response and long-term outcomes to second-line therapy for acute GVHD. / DeFilipp, Zachariah; Kim, Haesook T; Spyrou, Nikolaos; Katsivelos, Nikolaos; Kowalyk, Steven; Eng, Gilbert; Kasikis, Stelios; Beheshti, Rahnuma; Baez, Janna; Akahoshi, Yu; Ayuk, Francis; Choe, Hannah; Etra, Aaron; Grupp, Stephan A; Hexner, Elizabeth O; Hogan, William J; Kitko, Carrie L; Qayed, Muna; Reshef, Ran; Vasova, Ingrid; Zeiser, Robert; Young, Rachel; Holler, Ernst; Ferrara, James L M; Nakamura, Ryotaro; Levine, John E; Chen, Yi-Bin.
in: BLOOD ADV, Jahrgang 8, Nr. 13, 09.07.2024, S. 3488-3496.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The MAGIC algorithm probability predicts treatment response and long-term outcomes to second-line therapy for acute GVHD
AU - DeFilipp, Zachariah
AU - Kim, Haesook T
AU - Spyrou, Nikolaos
AU - Katsivelos, Nikolaos
AU - Kowalyk, Steven
AU - Eng, Gilbert
AU - Kasikis, Stelios
AU - Beheshti, Rahnuma
AU - Baez, Janna
AU - Akahoshi, Yu
AU - Ayuk, Francis
AU - Choe, Hannah
AU - Etra, Aaron
AU - Grupp, Stephan A
AU - Hexner, Elizabeth O
AU - Hogan, William J
AU - Kitko, Carrie L
AU - Qayed, Muna
AU - Reshef, Ran
AU - Vasova, Ingrid
AU - Zeiser, Robert
AU - Young, Rachel
AU - Holler, Ernst
AU - Ferrara, James L M
AU - Nakamura, Ryotaro
AU - Levine, John E
AU - Chen, Yi-Bin
N1 - © 2024 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.
PY - 2024/7/9
Y1 - 2024/7/9
N2 - The significance of biomarkers in second-line treatment for acute graft-versus-host disease (GVHD) has not been well characterized. We analyzed clinical data and serum samples at the initiation of second-line systemic treatment of acute GVHD from 167 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC) between 2016 and 2021. Sixty-two patients received ruxolitinib-based therapy, whereas 102 received other systemic agents. In agreement with prospective trials, ruxolitinib resulted in a higher day 28 (D28) overall response Frate than nonruxolitinib therapies (55% vs 31%, P = .003) and patients who received ruxolitinib had significantly lower nonrelapse mortality (NRM) than those who received nonruxolitinib therapies (point estimates at 2-year: 35% vs 61%, P = .002). Biomarker analyses demonstrated that the benefit from ruxolitinib was observed only in patients with low MAGIC algorithm probabilities (MAPs) at the start of second-line treatment. Among patients with a low MAP, those who received ruxolitinib experienced significantly lower NRM than those who received nonruxolitinib therapies (point estimates at 2-year: 12% vs 41%, P = .016). However, patients with high MAP experienced high NRM regardless of treatment with ruxolitinib or nonruxolitinib therapies (point estimates at 2-year: 67% vs 80%, P = .65). A landmark analysis demonstrated that the relationship between the D28 response and NRM largely depends on the MAP level at the initiation of second-line therapy. In conclusion, MAP measured at second-line systemic treatment for acute GVHD predicts treatment response and NRM. The outcomes of patients with high MAP are poor regardless of treatment choice, and ruxolitinib appears to primarily benefit patients with low MAP.
AB - The significance of biomarkers in second-line treatment for acute graft-versus-host disease (GVHD) has not been well characterized. We analyzed clinical data and serum samples at the initiation of second-line systemic treatment of acute GVHD from 167 patients from 17 centers of the Mount Sinai Acute GVHD International Consortium (MAGIC) between 2016 and 2021. Sixty-two patients received ruxolitinib-based therapy, whereas 102 received other systemic agents. In agreement with prospective trials, ruxolitinib resulted in a higher day 28 (D28) overall response Frate than nonruxolitinib therapies (55% vs 31%, P = .003) and patients who received ruxolitinib had significantly lower nonrelapse mortality (NRM) than those who received nonruxolitinib therapies (point estimates at 2-year: 35% vs 61%, P = .002). Biomarker analyses demonstrated that the benefit from ruxolitinib was observed only in patients with low MAGIC algorithm probabilities (MAPs) at the start of second-line treatment. Among patients with a low MAP, those who received ruxolitinib experienced significantly lower NRM than those who received nonruxolitinib therapies (point estimates at 2-year: 12% vs 41%, P = .016). However, patients with high MAP experienced high NRM regardless of treatment with ruxolitinib or nonruxolitinib therapies (point estimates at 2-year: 67% vs 80%, P = .65). A landmark analysis demonstrated that the relationship between the D28 response and NRM largely depends on the MAP level at the initiation of second-line therapy. In conclusion, MAP measured at second-line systemic treatment for acute GVHD predicts treatment response and NRM. The outcomes of patients with high MAP are poor regardless of treatment choice, and ruxolitinib appears to primarily benefit patients with low MAP.
KW - Humans
KW - Graft vs Host Disease/drug therapy
KW - Male
KW - Female
KW - Middle Aged
KW - Algorithms
KW - Adult
KW - Treatment Outcome
KW - Nitriles/therapeutic use
KW - Pyrazoles/therapeutic use
KW - Pyrimidines/therapeutic use
KW - Aged
KW - Acute Disease
KW - Biomarkers
KW - Young Adult
KW - Adolescent
KW - Hematopoietic Stem Cell Transplantation/adverse effects
U2 - 10.1182/bloodadvances.2024012561
DO - 10.1182/bloodadvances.2024012561
M3 - SCORING: Journal article
C2 - 38640197
VL - 8
SP - 3488
EP - 3496
JO - BLOOD ADV
JF - BLOOD ADV
SN - 2473-9529
IS - 13
ER -
