Clinical Trial Lab-Based Eligibility Criteria Disproportionately Excluded Non-White Patients With DLBCL From Study Participation

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A previous analysis by Khurana et al on the impact of inclusion/exclusion criteria in clinical trial design for patients with diffuse large B-cell lymphoma (DLBCL) found that up to 24% of patients treated with standard immunochemotherapy were excluded based on five lab-based criteria alone.

A new study by Khurana et al presented at the 2022 American Society of Hematology (ASH) Annual Meeting and Exposition (Abstract 850) investigated the association between clinical trial lab-based eligibility criteria and outcomes in newly diagnosed patients with DLBCL. The investigators found that some criteria—including a higher cutoff value of hemoglobin (9 g/dL or more)—disproportionately excluded non-White patients from clinical trials. In addition, overall survival was significantly inferior for patients ineligible for clinical trials based on lab criteria for Hispanic and/or non-White patients and non-Hispanic White patients.

Study Methodology

The researchers enrolled 2,510 newly diagnosed patients with DLBCL from 2015 to 2020 into the Lymphoma Epidemiology Outcomes (LEO) study from eight large academic centers across the United States. Clinical data, including baseline laboratory values, were abstracted from the patients’ medical records. The patients were prospectively followed for outcomes. All of the participants received an anthracycline plus CD20 antibody–based immunochemotherapy to standardize treatment.

Organ function parameters were identified from the exclusion criteria for hemoglobin, absolute neutrophil count, platelet count, creatinine, and bilirubin. Associations between trial eligibility and event-free survival and overall survival were evaluated using Kaplan-Meier curves. The researchers used the POLARIX trial as an example for outcomes because it is the most recently published front-line trial showing a benefit in clinical outcomes over R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone), the standard of care for DLBCL.


Of the 2,510 patients receiving front-line immunochemotherapy, 2,330 had three or more of the five lab-based values available in the LEO database and comprised the analysis set. The group included 1,972 non-Hispanic White participants (85%) and 272 Hispanic and/or non-White (12%) participants, with the rest of unknown race/ethnicity.

Compared to non-Hispanic White patients, Hispanic/non-White patients were younger at diagnosis (median 54 vs 64 years, P < .001), but were comparable for elevated lactate dehydrogenase (LDH) (56% vs 63%), B symptoms (32% vs 36%), bone marrow involvement (16% vs 18%), extranodal disease (26% vs 32%), and high-risk International Prognostic Index score (38% vs 37%).

Hemoglobin was significantly lower (mean + standard deviation) in the Hispanic/non-White (11.7 ± 2.3) vs non-Hispanic White (12.5 ± 2.2, P < .001) populations, whereas other lab values were similar between the two groups. Treatment regimens varied between the two groups, with more non-Hispanic White patients receiving R-CHOP (53% vs 38%, P < .001) and more Hispanic/non-White patients receiving R-EPOCH (rituximab, etoposide phosphate, prednisone, vincristine sulfate, cyclophosphamide, and doxorubicin hydrochloride; 38% vs 25%, P < .001).

In addition, the researchers found that within the LEO cohort, between 9% and 26% of the patients would have been excluded from recent front-line DLBCL clinical trials based on the five lab-based criteria alone. Of these, the ENGINE (26%), POLARIX (17%), and GOYA (17%) trials were the most restrictive.

Trials with a higher cutoff value for hemoglobin (9 g/dL or more) had a larger impact on Hispanic/Non-White population’s ineligibility. Overall survival was significantly inferior for patients ineligible for all trials based on lab criteria for both Hispanic/non-White and non-Hispanic White patients. Associations between ineligibility and poor outcomes were consistent across trial criteria and overall survival and event-free survival endpoints.

“This study confirms our previously reported association between trial lab-based eligibility criteria and outcomes in newly diagnosed DLBCL in a larger, contemporary, diverse cohort, and showed some criteria disproportionately limited eligibility for Hispanic/non-White patients. Further studies to evaluate the impact of each lab-based criteria on eligibility in different racial/ethnic populations are required. Future trial designs need to tailor eligibility criteria to be more inclusive of the Hispanic/non-White population,” concluded the study authors.

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