PET-CR as a potential surrogate endpoint in untreated DLBCL: meta-analysis and implications for clinical trial design

Kristine Broglio, Lale Kostakoglu, Carol Ward, Federico Mattiello, Denis Sahin, Tina Nielsen, Anna McGlothlin, Corrine F. Elliott, Thomas Witzig, Laurie H. Sehn, Marek Trnĕný, Umberto Vitolo, Maurizio Martelli, Margaret Foster, Barbara Wendelberger, Grzegorz Nowakowski, Donald A. Berry

Research output: Contribution to journalArticlepeer-review

Abstract

This study’s focus is the association of end-of-therapy (EOT) PET results with progression-free (PFS) and overall survival (OS) in patients with diffuse large B-cell lymphoma receiving first-line chemoimmunotherapy. We develop a Bayesian hierarchical model for predicting PFS and OS from EOT PET-complete response (PET-CR) using a literature-based meta-analysis of 20 treatment arms and a substudy of 4 treatment arms in 3 clinical trials for which we have patient-level data. The PET-CR rate in our substudy was 72%. The modeled estimates for hazard ratio (PET-CR/non-PET-CR) were 0.13 for PFS (95% CI 0.10, 0.16) and 0.10 for OS (CI 0.07, 0.12). Hazard ratios varied little by patient subtype and were confirmed by the overall meta-analysis. We link these findings to designing future clinical trials and show how our model can be used in adapting the sample size of a trial to accumulating results regarding treatment benefits on PET-CR and a survival endpoint.

Original languageEnglish (US)
JournalLeukemia and Lymphoma
DOIs
StateAccepted/In press - 2022

Keywords

  • Bayesian hierarchical model
  • clinical trial simulation
  • diffuse large B-cell lymphoma
  • end-of-treatment PET-complete response
  • meta-analysis
  • progression-free and overall survival

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

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