Elevated REG3α predicts refractory aGVHD in patients who received steroids-ruxolitinib as first-line therapy

• Published in: Annals of hematology Vol. 101; no. 3; pp. 621 - 630
• Main Authors: Yang, Jingjing, Peng, Bo, Wang, Lu, Li, Xin, Li, Fei, Jin, Xiangshu, Jia, Mingyu, Xu, Lingmin, Dou, Liping, Liu, Daihong
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01-03-2022; Springer Nature B.V
• Subjects: Adolescent; Adult; Biomarkers; Biomarkers - blood; Clinical trials; COVID-19; Disease prevention; Female; Graft versus host disease; Graft vs Host Disease - blood; Graft vs Host Disease - diagnosis; Graft vs Host Disease - prevention & control; Hematology; Hospitals; Humans; Inhibitor drugs; Leukemia; Male; Medicine; Medicine & Public Health; Middle Aged; Nitriles - therapeutic use; Oncology; Original; Original Article; Pancreatitis-Associated Proteins - blood; Prognosis; Prospective Studies; Pyrazoles - therapeutic use; Pyrimidines - therapeutic use; Remission (Medicine); Response rates; Stem cell transplantation; Steroids; Steroids - therapeutic use; Young Adult; Acute graft-versus-host disease; Ruxolitinib; Biomarker; First-line therapy
• ISSN: 0939-5555; 1432-0584
• DOI: 10.1007/s00277-021-04727-1

We started a single-arm, phase II, open-label, prospective clinical trial using steroids-ruxolitinib as the first-line therapy for intermediate- to high-risk aGVHD (NCT04397367). Here, we report the association of a biomarker panel (sST2, REG3α, sTNFR1, IL-6 and IL-8) with responses to GVHD therapy. The novel first-line therapy for 39 patients with newly diagnosed aGVHD consisted of 1 mg/kg methylprednisolone and 5 mg/day ruxolitinib. The serum concentrations of the biomarkers were prospectively detected at planned time points. Of the 39 patients, the complete response rate at day 28 was 82.05%. In patients who achieved CR, the concentrations of REG3α (
P
14
 = 0.01;
P
28
 = 0.10) and sTNFR1 (
P
14
 = 0.42;
P
28
 = 0.04) declined at day 14 and day 28 compared with the pre-enrolment levels. In refractory patients, the levels of REG3α at day 14 were higher than those pre-enrolment (
P
 = 0.04). REG3α (
P
 = 0.02) was elevated in the refractory patients compared with the patients achieving CR at day 14 after enrolment, while there was no significant difference in the levels of sST2, sTNFR1 or IL-6. Elevated REG3α levels may predict refractory aGVHD after novel first-line therapy with steroids-ruxolitinib.