Improving eligibility criteria for first-line trials for patients with DLBCL using a US-based Delphi-method survey

• Type of Material: Article
• Authors: Andrew R Harkins, Emory University; Sharvil P Patel, Emory University; Michelle J Lee, Morehouse University; Jeffrey Switchenko, Emory University; Stephen M Ansell, Mayo Clinic, Rochester; Nancy L Bartlett, Washington University; Kristie Blum, Emory University; Amanda F Cashen, Washington University; Carla Casulo, University of Rochester; Jonathan W Friedberg, University of Rochester; Patrick B Johnston, Mayo Clinic, Rochester; Brad S Kahl, Washington University; John P Leonard, Weill Cornell Medical College; Brian K Link, Washington University; Izidore S Lossos, University of Miami; Peter Martin, Weill Cornell Medical College; Matt J Maurer, Mayo Clinic, Rochester; Neha Mehta-Shah, Washington University; Patrick M Reagan, The University of Texas MD Anderson Cancer Center; Jason R Westin, The University of Texas MD Anderson Cancer Center; Jean Koff, Emory University; Christopher Flowers, Emory University
• Language: English
• Date: 2022-05-10
• Publisher: ELSEVIER
• Publication Version: Final Published Version
• Copyright Statement: © 2022 by The American Society of Hematology.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1182/bloodadvances.2021006504
• Title of Journal or Parent Work: BLOOD ADVANCES
• Volume: 6
• Issue: 9
• Start Page: 2745
• End Page: 2756
• Grant/Funding Information: The project described was supported in part by the National Cancer Institute (NCI) (K24 CA208132 award for mentored patient-oriented research in lymphoma) and CPRIT Award RR190079 (C.R.F.).; This work was supported by grants from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (grants TL1TR002382 and UL1TR002378) (R.A.H.). C.R.F. is a Cancer Prevention and Research Institute of Texas (CPRIT) Scholar of Cancer Research; Research reported in this publication was supported in part by the Biostatistics Shared Resource of Winship Cancer Institute of Emory University and NIH/NCI under award number P30CA138292.
• Keywords: CLINICAL-TRIALS; RITUXIMAB PLUS CYCLOPHOSPHAMIDE; B-CELL LYMPHOMA; Life Sciences & Biomedicine; R-CHOP; PHASE-III; PREVIOUSLY UNTREATED PATIENTS; CHOP-LIKE CHEMOTHERAPY; OPEN-LABEL; Hematology; RANDOMIZED CONTROLLED-TRIAL; ELDERLY-PATIENTS; Science & Technology
• Research Categories: Health Sciences, Medicine and Surgery; Health Sciences, Oncology

Abstract

Recent first-line randomized controlled trials (RCTs) for patients with diffuse large B-cell lymphoma (DLBCL) have shown negative results, which may be due in part to onerous eligibility criteria limiting enrollment of poor-risk patients who require immediate treatment. We conducted a Delphi-method survey with lymphoma experts in the United States to define recommendations for essential and potentially unnecessary enrollment criteria for modern first-line DLBCL RCTs aimed at increasing clinical diversity of ensuing study groups. We first tabulated enrollment criteria from 19 DLBCL RCTs spanning the rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) era to identify common eligibility criteria from prior DLBCL RCTs for inclusion in the Delphi-method survey. We tabulated 451 total eligibility criteria comprising 51 criterion categories across 19 first-line DLBCL RCTs in the R-CHOP era. We then surveyed lymphoma clinical trial experts representing 8 academic medical centers in the United States regarding essential and unnecessary eligibility criteria for modern DLBCL RCTs. Seventeen of 29 invited clinical investigators completed the round-1 questionnaire (response rate, of 58.6%), 15 of 17 round-1 participants (88.2%) completed the round-2 survey, and all round-1 participants reviewed finalized recommendations for eligibility criteria for modern first-line DLBCL RCTs. We defined consensus recommendations for 31 modernized eligibility criteria including threshold values for 10 quantitative eligibility criteria aimed at facilitating enrollment of a clinically diverse study population in first-line DLBCL RCTs designed to improve standard-of-care therapy.