title: Response assessment in lymphoma: Concordance between independent central review and local evaluation in a clinical trial setting.
abstract: Independent central review of clinical imaging remains the standard for oncology clinical trials with registration potential. A limited independent central review strategy has been proposed for solid tumor trials based on concordance between central and local evaluation of response. Concordance between independent central review and local evaluation of response in hematological malignancies is not known.
  
  
  
  We retrospectively evaluated concordance between prospectively performed central and local assessments of response using the Revised Response Criteria for Malignant Lymphoma across two international, open-label, single-arm, registration studies of brentuximab vedotin in patients with relapsed or refractory Hodgkin lymphoma (N = 102) or systemic anaplastic large-cell lymphoma (N = 58).
  
  
  
  Overall objective response rates were similar between assessors for both the trial in Hodgkin lymphoma (75% independent central review, 72% local evaluation) and the trial in anaplastic large-cell lymphoma (86% independent central review, 83% local evaluation). Patient-specific objective response concordance was also substantial (Hodgkin lymphoma: kappa = 0.68; anaplastic large-cell lymphoma: kappa = 0.74). Median progression-free survival was similar between assessors for patients with anaplastic large-cell lymphoma (14.3 months by independent central review (95% confidence interval: 6.9, -); 14.5 months by local evaluation (95% confidence interval: 9.4, -)), but longer by local evaluation in patients with Hodgkin lymphoma (5.8 months by independent central review (95% confidence interval: 5.0, 9.0); 9.0 months by local evaluation (95% confidence interval: 7.1, 12.0)). Median duration of response was longer by local evaluation in both malignancies, which was primarily attributable to earlier computed tomography and positron emission tomography-based scoring of progression by independent central review.
  
  
  
  A limited independent review audit strategy for clinical trials of some lymphomas appears feasible and practical based on substantial concordance in assessments of overall objective response by central and local evaluation in two international, prospective, registration trials in lymphoma. Some variability between assessors in the time-to-event endpoints was observed, which appeared attributable to earlier assignments of progression by independent central review compared with local evaluation.
authors.affiliation: The University of Washington/Fred Hutchison Cancer Research Center, Seattle Cancer Care Alliance, Seattle, WA, USA agopal@u.washington.edu.
authors.forename: Ajay K
authors.initials: AK
authors.lastname: Gopal
authors.affiliation: Thomas Jefferson University, Philadelphia, PA, USA.
authors.forename: Barbara
authors.initials: B
authors.lastname: Pro
authors.affiliation: The University of British Columbia, Vancouver, BC, Canada.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Connors
authors.affiliation: Memorial Sloan Kettering Cancer Center, New York, NY, USA.
authors.forename: Anas
authors.initials: A
authors.lastname: Younes
authors.affiliation: University Hospital of Cologne, Cologne, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Engert
authors.affiliation: University of Washington Medical Center, Seattle, WA, USA.
authors.forename: Andrei R
authors.initials: AR
authors.lastname: Shustov
authors.affiliation: Millenium Pharmaceuticals, Inc., Cambridge, MA, a wholly owned subsidiary of Takeda Pharmaceuticals Limited, USA.
authors.forename: Xuedong
authors.initials: X
authors.lastname: Chi
authors.affiliation: Seattle Genetics, Inc., Bothell, WA, USA.
authors.forename: Emily K
authors.initials: EK
authors.lastname: Larsen
authors.affiliation: Seattle Genetics, Inc., Bothell, WA, USA.
authors.forename: Dana A
authors.initials: DA
authors.lastname: Kennedy
authors.affiliation: Seattle Genetics, Inc., Bothell, WA, USA.
authors.forename: Eric L
authors.initials: EL
authors.lastname: Sievers
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018450:Disease Progression; D018572:Disease-Free Survival; D006689:Hodgkin Disease / Q000188:drug therapy*; D006801:Humans; D018796:Immunoconjugates / Q000627:therapeutic use*; D017728:Lymphoma, Large-Cell, Anaplastic / Q000188:drug therapy*; D009664:Norway; D011446:Prospective Studies; D012189:Retrospective Studies
chemical_list: D000970:Antineoplastic Agents; D018796:Immunoconjugates
keywords: Cheson; Response criteria; computed tomography/positron emission tomography; concordance; independent central review; local evaluation; lymphoma