title: Treatment change as a predictor of outcome among patients with classic chronic graft-versus-host disease.
abstract: We analyzed outcomes for 668 patients who had systemic treatment for chronic graft-versus-host disease (cGVHD) to assess the utility of early treatment change for exacerbation of cGVHD as a surrogate for survival endpoints in clinical trials. Fifty-six percent of patients had treatment change within 2 years after diagnosis of cGVHD. The median onset of treatment change was 4.4 months (range: 0.3-50 months). The cumulative incidence of nonrelapse mortality (NRM) at 2 years was 16%, and overall survival (OS) at 2 years was 74%. In time-dependent Cox models, treatment change was associated with an increase in risk of NRM (hazard ratio, 2.53; 95% confidence interval, 1.7-3.7; P < .0001). The hazard ratio was attenuated by 6% per month of delay in treatment change. Our results confirm that exacerbation of cGVHD is associated with an increased risk of NRM and with decreased OS, but the strength of this association is not large enough to allow the use of early exacerbation as a surrogate for survival endpoints in clinical trials. Other measures of clinical benefit, such as response, will need to be developed as endpoints in phase II trials for patients with cGVHD.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington 98109-1024, USA. mflowers@fhcrc.org
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: Barry
authors.initials: B
authors.lastname: Storer
authors.forename: Paul
authors.initials: P
authors.lastname: Carpenter
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Rezvani
authors.forename: Afonso C
authors.initials: AC
authors.lastname: Vigorito
authors.forename: Paulo V
authors.initials: PV
authors.lastname: Campregher
authors.forename: Carina
authors.initials: C
authors.lastname: Moravec
authors.forename: Hans-Peter
authors.initials: HP
authors.lastname: Kiem
authors.forename: Matthew
authors.initials: M
authors.lastname: Fero
authors.forename: George
authors.initials: G
authors.lastname: Georges
authors.forename: Edus
authors.initials: E
authors.lastname: Warren
authors.forename: Stephanie
authors.initials: S
authors.lastname: Lee
authors.forename: Jean E
authors.initials: JE
authors.lastname: Sanders
authors.forename: Fred
authors.initials: F
authors.lastname: Appelbaum
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D015331:Cohort Studies; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D015994:Incidence; D007223:Infant; D008297:Male; D008875:Middle Aged; D033581:Stem Cell Transplantation; D015996:Survival Rate