title: Extracorporeal photopheresis as second-line treatment for acute graft-versus-host disease: impact on six-month freedom from treatment failure.
abstract: Second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease remains ill-defined, due to limited efficacy of drugs and evolving clinical trial endpoints. Six-month freedom from treatment failure has been proposed as a novel clinical trial endpoint and is defined by the absence of death, malignancy relapse/progression, or addition of a next line of systemic immunosuppressive therapy within 6 months of intervention and prior to diagnosis of chronic graft-versus-host disease. We analyzed the 6-month freedom from treatment failure endpoint in 128 patients enrolled from three centers who were treated with extracorporeal photopheresis as second-line therapy for acute graft-versus-host disease. The incidence of 6-month freedom from treatment failure was 77.3% with a 2-year survival rate of 56%. Corticosteroid dose or response status at onset of second-line therapy did not influence outcome. Higher grade of acute graft-versus-host disease (grade 2 versus grades 3-4) at onset of photopheresis predicted for poor outcome as measured by survival (hazard ratio 2.78, P<0.001), non-relapse mortality (hazard ratio 2.78, P=0.001) and 6-month freedom from treatment failure (hazard ratio 3.05, P<0.001). For the 91 patients who achieved 6-month freedom from treatment failure, 1-year, 2-year and 3-year survival rates were 78.9%, 70.8% and 69.5%, respectively. Six-month freedom from treatment failure is a reasonable early surrogate for outcome and should be considered as a clinical trial endpoint. This study demonstrates the durable effect of photopheresis as second-line therapy for corticosteroid-refractory or -dependent acute graft-versus-host disease using 6-month freedom from treatment failure as the primary endpoint.
authors.affiliation: Nottingham University Hospitals NHS Trust, UK.
authors.forename: Emma
authors.initials: E
authors.lastname: Das-Gupta
authors.affiliation: Medical University of Vienna, Austria.
authors.forename: Hildegard
authors.initials: H
authors.lastname: Greinix
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Ryan
authors.initials: R
authors.lastname: Jacobs
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Bipin N
authors.initials: BN
authors.lastname: Savani
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Engelhardt
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA.
authors.forename: Adetola
authors.initials: A
authors.lastname: Kassim
authors.affiliation: Medical University of Vienna, Austria.
authors.forename: Nina
authors.initials: N
authors.lastname: Worel
authors.affiliation: Medical University of Vienna, Austria.
authors.forename: Robert
authors.initials: R
authors.lastname: Knobler
authors.affiliation: Nottingham University Hospitals NHS Trust, UK.
authors.forename: Nigel
authors.initials: N
authors.lastname: Russell
authors.affiliation: Department of Medicine, Vanderbilt University Medical Center, Nashville, TN, USA madan.jagasia@vanderbilt.edu.
authors.forename: Madan
authors.initials: M
authors.lastname: Jagasia
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000368:Aged; D002423:Cause of Death; D002908:Chronic Disease; D005260:Female; D006086:Graft vs Host Disease / Q000175:diagnosis / Q000209:etiology / Q000401:mortality / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D017893:Photopheresis / Q000379:methods; D012008:Recurrence; D019233:Retreatment; D013997:Time Factors; D014184:Transplantation, Homologous; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000305:Adrenal Cortex Hormones; D007166:Immunosuppressive Agents