Response assessment in lymphoma: Concordance between independent central review and local evaluation in a clinical trial setting

Ajay K. Gopal*, Barbara Pro, Joseph M. Connors, Anas Younes, Andreas Engert, Andrei R. Shustov, Xuedong Chi, Emily K. Larsen, Dana A. Kennedy, Eric L. Sievers

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

Abstract

Background: 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. Methods: 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). Results: 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. Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)545-554
Number of pages10
JournalClinical Trials
Volume13
Issue number5
DOIs
StatePublished - Oct 1 2016

Keywords

  • Cheson
  • Response criteria
  • computed tomography/positron emission tomography
  • concordance
  • independent central review
  • local evaluation
  • lymphoma

ASJC Scopus subject areas

  • Pharmacology

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