Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May 20;39(15):1641-1649.
doi: 10.1200/JCO.20.01935. Epub 2021 Feb 2.

Impact of Organ Function-Based Clinical Trial Eligibility Criteria in Patients With Diffuse Large B-Cell Lymphoma: Who Gets Left Behind?

Arushi Khurana  1 , Raphael Mwangi  2 , Grzegorz S Nowakowski  1 , Thomas M Habermann  1 , Stephen M Ansell  1 , Betsy R LaPlant  2 , Brian K Link  3 , James R Cerhan  2 , Matthew J Maurer  2 , Thomas E Witzig  1
Affiliations

Impact of Organ Function-Based Clinical Trial Eligibility Criteria in Patients With Diffuse Large B-Cell Lymphoma: Who Gets Left Behind?

Arushi Khurana et al. J Clin Oncol. .

Abstract

Purpose: Exclusion of patients needing urgent treatment or requiring novel biomarkers before enrollment has impacted the ability to enroll real-world patients in frontline trials of diffuse large B-cell lymphoma (DLBCL). The impact of baseline organ function-based eligibility criteria on this effect and clinical trial exclusion is less well-understood.

Methods: Consecutive patients with newly diagnosed lymphoma were enrolled from 2002 to 2015 into the Molecular Epidemiology Resource (MER) of the University of Iowa and Mayo Clinic Lymphoma Specialized Program of Research Excellence. The current analysis includes 1,265 patients with DLBCL receiving standard immunochemotherapy. Organ function parameters were identified from criteria for hemoglobin, absolute neutrophil count, platelet count, creatinine clearance, and bilirubin, as reported in frontline DLBCL trials. Abstracted laboratory values from MER were used to determine the percent (%) of patients excluded. Outcomes and cause-of-death analyses comparing ineligible and eligible groups in MER were conducted. An interactive online tool was developed to estimate exclusions based on organ function for future trial design.

Results: Between 9% and 24% of MER patients with DLBCL receiving standard immunochemotherapy were excluded on the basis of baseline organ function alone. Ineligible patients based on organ function had significantly inferior event-free survival (hazard ratios, 1.67-2.16), overall survival (hazard ratios, 1.87-2.56), and event-free survival at 24 months (odds ratio, 1.71-2.16). Ineligible patients were more likely to die from lymphoma progression than increased therapy-related complications.

Conclusion: Current national and international trials exclude up to 24% of patients from participation on the basis of organ function alone. A significant difference in the outcomes, notably lymphoma-related death, suggests issues with generalization and potential exclusion of high-risk patients. These data will help future clinical trial development and meet US Food and Drug Administration and ASCO recommendations to increase trial accrual.

PubMed Disclaimer

Conflict of interest statement

Grzegorz S. NowakowskiConsulting or Advisory Role: Celgene, MorphoSys, Genentech, Selvita, Debiopharm Group, Kite/GileadResearch Funding: Celgene, NanoString Technologies, MorphoSys Thomas M. HabermannConsulting or Advisory Role: Celgene, Kite/Gilead Stephen M. AnsellHonoraria: WebMD, Research to PracticeResearch Funding: Bristol-Myers Squibb, Seattle Genetics, Affimed Therapeutics, Regeneron, Trillium Therapeutics, AI Therapeutics, ADC Therapeutics Brian K. LinkConsulting or Advisory Role: Genentech/Roche, Abbvie, MEI PharmaResearch Funding: Pharmacyclics/Janssen, Genentech/AbbvieTravel, Accommodations, Expenses: Genentech/Roche James R. CerhanConsulting or Advisory Role: JanssenResearch Funding: NanoString Technologies, Celgene, Genentech Matthew J. MaurerConsulting or Advisory Role: MorphoSys, Kite Pharma, PfizerResearch Funding: Celgene, NanoString Technologies, Genentech, Morphosys Thomas E. WitzigConsulting or Advisory Role: Karyopharm Therapeutics, Abbvie/Genentech, Seattle Genetics, Celgene, Incyte, Epizyme, Cellectar, Tessa Therapeutics, Portola Pharmaceuticals, MorphoSys, ADC TherapeuticsResearch Funding: Celgene, Acerta Pharma, Kura Oncology, Acrotech Biopharma, Karyopharm TherapeuticsPatents, Royalties, Other Intellectual Property: I am a co-inventor on a patent application filed by Mayo Clinic and pending on the combination of CRM1 inhibitors with salicylates. Please note—simply filed—not even close to being granted.No other potential conflicts of interest were reported.

Figures

FIG 1.
FIG 1.
Flow diagram showing the patient selection process in the study.
FIG 2.
FIG 2.
ENGINE trial (A) OS, (B) EFS, and (C) cause of death between eligible (solid line) and ineligible (dotted line) MER patients. EFS, event-free survival; MER, Molecular Epidemiology Resource; OS, Overall survival.
See this image and copyright information in PMC

References

    1. Murthy VH, Krumholz HM, Gross CP.Participation in cancer clinical trials: Race-, sex-, and age-based disparities J Am Med Assoc 2912720–27262004 - PubMed
    1. Nass SJ, Moses HL, Mendelsohn J. A National Cancer Clinical Trials System for the 21st Century: Reinvigorating the NCI Cooperative Group Program. Washington, DC: National Academies Press; 2010. - PubMed
    1. Unger JM, Hershman DL, Fleury ME, et al. Association of patient comorbid conditions with cancer clinical trial participation JAMA Oncol 5326–3332019 - PMC - PubMed
    1. Unger JM, Vaidya R, Hershman DL, et al. Systematic review and meta-analysis of the magnitude of structural, clinical, and physician and patient barriers to cancer clinical trial participation J Natl Cancer Inst 111245–2552019 - PMC - PubMed
    1. Unger JM, Barlow WE, Martin DP, et al. Comparison of survival outcomes among cancer patients treated in and out of clinical trials. J Natl Cancer Inst. 2014;106:dju002. - PMC - PubMed

Publication types