Study: Patients of Racial, Ethnic Minority Groups With Diffuse Large B-cell Lymphoma Are Often Excluded From Frontline Therapy Trials

Patients with diffuse large B-cell lymphoma (DLBCL) may experience worse clinical outcomes and higher rates of death from worsening lymphoma if they are excluded from studies that test frontline novel therapies, explained investigators presenting a poster titled “Evaluating the Impact of Lab-Based Eligibility Criteria By Race/Ethnicity in Frontline Clinical Trials for Diffuse Large B-Cell Lymphoma (DLBCL): A LEO Cohort Analysis” at the 64th American Society of Hematology (ASH) Annual Meeting and Exhibition in New Orleans, Louisiana. According to the investigators, as many as 24% of DLBCL patients treated with standard immunochemotherapy (IC) are excluded from frontline trials.

“We observed several key clinical differences by race and ethnicity in patients with DLBCL when enrolled in the LEO cohort,” said study investigator and ASH poster presenter Matthew Maurer, DrMed, the lead faculty statistician for the lymphoma research program at Mayo Clinic, the co-director of the Biostatistics and Bioinformatics Core of the University of Iowa and Mayo Clinic Lymphoma Specialized Programs of Research Excellence (SPORE) grant, and the director of the Statistics and Informatics Core of the multicenter Lymphoma Epidemiology of Outcomes (LEO) Cohort, during a press briefing. Maurer explained that there is anurgent need to diversify participants in these clinical trials, which would increase the widespread benefit of new therapies that treat DLBCL.

Further, a recent analysis conducted by Maurer and a team of investigators showed that more than 50% of non-Hispanic White (NHW) participants would have received a novel treatment regimen, compared to 38% of Hispanic and/or non-White (H/NW) participants.

During the trial, investigators enrolled newly diagnosed DLBCL patients in the Lymphoma Epidemiology Outcomes (LEO) cohort from 2015 to 2020 to evaluate the impact of race and ethnicity on lab-based trial eligibility criteria. The LEO cohort consisted of 8 trials spanning across 8 large academic US centers. Trial participants included 1972 NHW, 272 H/NW, and others of unknown race or ethnicity.

The investigators gave all patients the standard treatment. The patients were then evaluated for 5 lab-based exclusion criteria, including organ-function parameters such as hemoglobin, absolute neutrophil count, platelet count, creatinine, and bilirubin, used to identify participants for a previous frontline trial.

Maurer noted that evaluating current LEO participants with this previously established criteria would determine who among the LEO cohort would have been eligible to participate in that previous frontline trial.

Racial minorities, particularly Black and African American patients, were most at risk of being excluded from a novel therapy clinical trial for DLCBL. Additionally, those participants who were excluded from the trial also had a worse risk of dying from traditional standard therapy.

“If we look at all 5 lab values (using the cutoffs from 3 recent industry phase 3 clinical trials), between 17% and 26% of patients with DLBCL enrolled in LEO would have been excluded,” Maurer said.

Investigators also looked at associations of race and ethnicity with event-free survival (EFS) and overall survival (OS). The results showed that the OS and EFS were poorer for patients who were unable to participate in the frontline trials.

Further, the average age of patients who received a DLBCL diagnosis was 10 years younger in H/NW participants compared to NHWs. Additionally, hemoglobin levels were significantly lower in the H/NW participants; trial entry criteria noted plans to exclude participants with lower hemoglobin levels.

H/NW and NHS subgroups also presented comparable elevated LDH protein levels of 56% and 63%, respectively. Percentages were also comparable for B-symptoms (32% and 36%), bone marrow involvement (16% and 18%), extranodal disease (26% and 32%), and high-risk IPI (38% and 37%).

Because of these results, the investigators at ASH noted there is a need to do further evaluation on how lab-based criteria impacts the eligibility of certain racial/ethnic populations and subsequently expand the criteria to include H/NWs.

Additionally, the team of investigators calls for better biomarkers such as disease burden, versus comorbidities, as well as thoughtful clinical trial designs, which Maurer noted are desperately needed to improve inclusivity in clinical trials assessing therapies in DLBCL.

Reference

Khurana A, Mwangi R, Nastoupil L, et al. 850 Evaluating the Impact of Lab-Based Eligibility Criteria By Race/Ethnicity in Frontline Clinical Trials for Diffuse Large B-Cell Lymphoma (DLBCL): A LEO Cohort Analysis. ASH. December 12, 2022. Accessed on December 12, 2022. https://ash.confex.com/ash/2022/webprogram/Paper169433.html