Journal article
Impact of Organ Function–Based Clinical Trial Eligibility Criteria in Patients With Diffuse Large B-Cell Lymphoma: Who Gets Left Behind?
Journal of clinical oncology, Vol.39(15), pp.1641-1649
05/20/2021
DOI: 10.1200/JCO.20.01935
PMCID: PMC8274741
PMID: 33529046
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.
Details
- Title: Subtitle
- Impact of Organ Function–Based Clinical Trial Eligibility Criteria in Patients With Diffuse Large B-Cell Lymphoma: Who Gets Left Behind?
- Creators
- Arushi Khurana - Mayo ClinicRaphael Mwangi - Mayo Clinic in FloridaGrzegorz S. Nowakowski - Mayo ClinicThomas M. Habermann - Mayo ClinicStephen M. Ansell - Mayo ClinicBetsy R. LaPlant - Mayo Clinic in FloridaBrian K. Link - University of IowaJames R. Cerhan - Mayo ClinicMatthew J. Maurer - Department of Health Sciences Research, Mayo Clinic, Rochester, MNThomas E. Witzig - Mayo Clinic
- Resource Type
- Journal article
- Publication Details
- Journal of clinical oncology, Vol.39(15), pp.1641-1649
- DOI
- 10.1200/JCO.20.01935
- PMID
- 33529046
- PMCID
- PMC8274741
- ISSN
- 0732-183X
- eISSN
- 1527-7755
- Language
- English
- Date published
- 05/20/2021
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Epidemiology; Internal Medicine
- Record Identifier
- 9984359837002771
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