Treatment change as a predictor of outcome among patients with classic chronic graft-versus-host disease.
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.
Flowers
Mary E D
ME
Division of Clinical Research, Fred Hutchinson Cancer Research Center, University of Washington School of Medicine, Seattle, Washington 98109-1024, USA. mflowers@fhcrc.org
Storer
Barry
B
Carpenter
Paul
P
Rezvani
Andrew R
AR
Vigorito
Afonso C
AC
Campregher
Paulo V
PV
Moravec
Carina
C
Kiem
Hans-Peter
HP
Fero
Matthew
M
Georges
George
G
Warren
Edus
E
Lee
Stephanie
S
Sanders
Jean E
JE
Appelbaum
Fred
F
Martin
Paul J
PJ
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