Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

Erin Gatza; Thomas Braun; John E. Levine; James L.M. Ferrara; Shuang Zhao; Tianyi Wang; Lawrence Chang; Andrew Harris; Attaphol Pawarode; Carrie Kitko; John M. Magenau; Gregory A. Yanik; Daniel R. Couriel; Steven Goldstein; James Connelly; Pavan Reddy; Sophie Paczesny; Sung Won Choi

doi:10.1016/j.bbmt.2014.05.023

Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

Erin Gatza, Thomas Braun, John E. Levine, James L.M. Ferrara, Shuang Zhao, Tianyi Wang, Lawrence Chang, Andrew Harris, Attaphol Pawarode, Carrie Kitko, John M. Magenau, Gregory A. Yanik, Daniel R. Couriel, Steven Goldstein, James Connelly, Pavan Reddy, Sophie Paczesny, Sung Won Choi

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

18 Scopus citations

Abstract

Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28days. Study patients (n=34) had a median age of 51years (range, 10 to 67years) and had undergone unrelated (n=22) or related (n=12) donor HSCT. Study patients were treated with etanercept (4mg/kg, maximum 25mg/dose) twice weekly for 4 to 8weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P=08) and 18% (3% versus 18%, P=05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P=06) and regenerating islet-derived 3-alpha (P=01) 28days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375.

Original language	English
Pages (from-to)	1426-1434
Number of pages	9
Journal	Biology of Blood and Marrow Transplantation
Volume	20
Issue number	9
DOIs	https://doi.org/10.1016/j.bbmt.2014.05.023
State	Published - Sep 2014
Externally published	Yes

Keywords

Clinical trial
Etanercept
Grade 1 acute
Graft-versus-host disease
Hematopoietic stem cell transplantation

Access to Document

10.1016/j.bbmt.2014.05.023

Cite this

Gatza, E., Braun, T., Levine, J. E., Ferrara, J. L. M., Zhao, S., Wang, T., Chang, L., Harris, A., Pawarode, A., Kitko, C., Magenau, J. M., Yanik, G. A., Couriel, D. R., Goldstein, S., Connelly, J., Reddy, P., Paczesny, S., & Choi, S. W. (2014). Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation. Biology of Blood and Marrow Transplantation, 20(9), 1426-1434. https://doi.org/10.1016/j.bbmt.2014.05.023

@article{319a7395e3fb45deac1e82175d1c577c,

title = "Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation",

abstract = "Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28days. Study patients (n=34) had a median age of 51years (range, 10 to 67years) and had undergone unrelated (n=22) or related (n=12) donor HSCT. Study patients were treated with etanercept (4mg/kg, maximum 25mg/dose) twice weekly for 4 to 8weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P=08) and 18% (3% versus 18%, P=05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P=06) and regenerating islet-derived 3-alpha (P=01) 28days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375.",

keywords = "Clinical trial, Etanercept, Grade 1 acute, Graft-versus-host disease, Hematopoietic stem cell transplantation",

author = "Erin Gatza and Thomas Braun and Levine, {John E.} and Ferrara, {James L.M.} and Shuang Zhao and Tianyi Wang and Lawrence Chang and Andrew Harris and Attaphol Pawarode and Carrie Kitko and Magenau, {John M.} and Yanik, {Gregory A.} and Couriel, {Daniel R.} and Steven Goldstein and James Connelly and Pavan Reddy and Sophie Paczesny and Choi, {Sung Won}",

note = "Funding Information: Financial disclosure: This study was supported by grants to S.W.C. from St. Baldrick's Foundation , United States, the Michigan Institute for Clinical and Health Research , and the National Institutes of Health ( 1K23AI091623 ) and to S.P. from the National Institutes of Health (R01CA174667). S.W.C. is an A. Alfred Taubman Institute/Edith Briskin Emerging Scholar. ",

year = "2014",

month = sep,

doi = "10.1016/j.bbmt.2014.05.023",

language = "English",

volume = "20",

pages = "1426--1434",

journal = "Biology of Blood and Marrow Transplantation",

issn = "1083-8791",

publisher = "Elsevier B.V.",

number = "9",

}

Gatza, E, Braun, T, Levine, JE , Ferrara, JLM, Zhao, S, Wang, T, Chang, L, Harris, A, Pawarode, A, Kitko, C, Magenau, JM, Yanik, GA, Couriel, DR, Goldstein, S, Connelly, J, Reddy, P, Paczesny, S & Choi, SW 2014, 'Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation', Biology of Blood and Marrow Transplantation, vol. 20, no. 9, pp. 1426-1434. https://doi.org/10.1016/j.bbmt.2014.05.023

TY - JOUR

T1 - Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

AU - Gatza, Erin

AU - Braun, Thomas

AU - Levine, John E.

AU - Ferrara, James L.M.

AU - Zhao, Shuang

AU - Wang, Tianyi

AU - Chang, Lawrence

AU - Harris, Andrew

AU - Pawarode, Attaphol

AU - Kitko, Carrie

AU - Magenau, John M.

AU - Yanik, Gregory A.

AU - Couriel, Daniel R.

AU - Goldstein, Steven

AU - Connelly, James

AU - Reddy, Pavan

AU - Paczesny, Sophie

AU - Choi, Sung Won

N1 - Funding Information: Financial disclosure: This study was supported by grants to S.W.C. from St. Baldrick's Foundation , United States, the Michigan Institute for Clinical and Health Research , and the National Institutes of Health ( 1K23AI091623 ) and to S.P. from the National Institutes of Health (R01CA174667). S.W.C. is an A. Alfred Taubman Institute/Edith Briskin Emerging Scholar.

PY - 2014/9

Y1 - 2014/9

N2 - Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28days. Study patients (n=34) had a median age of 51years (range, 10 to 67years) and had undergone unrelated (n=22) or related (n=12) donor HSCT. Study patients were treated with etanercept (4mg/kg, maximum 25mg/dose) twice weekly for 4 to 8weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P=08) and 18% (3% versus 18%, P=05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P=06) and regenerating islet-derived 3-alpha (P=01) 28days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375.

AB - Clinical diagnosis of grade 1 acute graft-versus-host disease (GVHD) marks the beginning of a potentially progressive and fatal course of GVHD after hematopoietic stem cell transplantation (HSCT). However, interventional studies to treat early GVHD are lacking. We conducted a single-arm prospective phase II trial to test the hypothesis that treatment of newly diagnosed grade 1 acute GVHD with etanercept and topical corticosteroids would reduce progression to grade 2 to 4 within 28days. Study patients (n=34) had a median age of 51years (range, 10 to 67years) and had undergone unrelated (n=22) or related (n=12) donor HSCT. Study patients were treated with etanercept (4mg/kg, maximum 25mg/dose) twice weekly for 4 to 8weeks. Ten of 34 patients (29%) progressed to grade 2 to 4 acute GVHD within 28days. The cumulative incidence of grade 2 to 4 and grade 3 to 4 acute GVHD at 1year was 41% and 3%, respectively. Nonrelapse mortality was 19% and overall survival was 63% at 2years. Among a contemporaneous control cohort of patients who were diagnosed with grade 1 acute GVHD and treated with topical corticosteroids but not etanercept during the study period, 12 of 28 patients (43%) progressed to grade 2 to 4 GVHD within 28days, with a 1-year incidence of grade 2 to 4 GVHD and grade 3 to 4 GVHD of 61% (41% versus 61%, P=08) and 18% (3% versus 18%, P=05), respectively. Patients treated with etanercept also experienced less increase in GVHD plasma biomarkers suppression of tumorigenicity 2 (P=06) and regenerating islet-derived 3-alpha (P=01) 28days after grade 1 acute GVHD diagnosis compared with contemporaneous control patients. This study was terminated early because of poor accrual. Future prospective studies are needed to identify patients with grade 1 acute GVHD at risk of swift progression to more severe GVHD and to establish consensus for the treatment of grade 1 acute GVHD. This trial is registered with ClinicalTrials.gov, number NCT00726375.

KW - Clinical trial

KW - Etanercept

KW - Grade 1 acute

KW - Graft-versus-host disease

KW - Hematopoietic stem cell transplantation

UR - http://www.scopus.com/inward/record.url?scp=84905565069&partnerID=8YFLogxK

U2 - 10.1016/j.bbmt.2014.05.023

DO - 10.1016/j.bbmt.2014.05.023

M3 - Article

C2 - 24892263

AN - SCOPUS:84905565069

SN - 1083-8791

VL - 20

SP - 1426

EP - 1434

JO - Biology of Blood and Marrow Transplantation

JF - Biology of Blood and Marrow Transplantation

IS - 9

ER -

Etanercept plus topical corticosteroids as initial therapy for grade one acute graft-versus-host disease after allogeneic hematopoietic cell transplantation

Abstract

Keywords

Access to Document

Fingerprint

Cite this