NEW ORLEANS, La.—With an annual incidence of 4.68 cases per 100,000, diffuse large B-cell lymphoma (DLBCL) accounts for 30%-40% of all US cases of non-Hodgkin lymphoma.
Yet Black and Hispanic people with DLBCL are much less likely than White patients to qualify for clinical trials to test potential therapies, according to a new study led by Arushi Khurana, MBBS, a hematologist-oncologist at the Mayo Clinic in Rochester, Minnesota.
The study, “Evaluating the Impact of Lab-Based Eligibility Criteria by Race/Ethnicity in Frontline Clinical Trials for Diffuse Large B-Cell Lymphoma,” was presented by Mayo Clinic statistician Matthew Maurer, DSc, during the 64th ASH Annual Meeting and Exposition here.
It shows that even though clinical trials don’t directly exclude patients based on race or ethnicity, Black and Hispanic patients with DLBCL are less likely to meet criteria based on levels of hemoglobin, neutrophil count, platelet count, creatinine clearance, and bilirubin—all of which help determine trial eligibility.
“We found that 24% of patients get excluded based on these 5 lab‑based criteria. That’s a lot,” Dr. Khurana said. “These are patients who can come to our academic center, and they’re able to consent for research. This is not a matter of access. If we restrict patients who still have access and were able to make it, then that’s something we’re doing wrong—and we need to rectify it.”
Trial Inclusion Criteria Growing More Restrictive
Dr. Khurana, a native of India, said she got interested in hematology thanks to her mother, a professor of physiology who specializes in rare disorders. In addition, her grandmother was diagnosed with DLBCL while Dr. Khurana was a second-year student at Maulana Azad Medical College in New Delhi.
“I’ve seen her journey pretty up close and personal, sitting with her while she went through chemotherapy,” Dr. Khurana said. “She experienced quite a bit of toxicity, and that touched me personally. So I’ve always been inclined towards trying to make outcomes better for lymphoma patients.”
DLBCL, the most common form of non-Hodgkin lymphoma, ranks as the seventh most common cancer for both male and female patients in the United States. About 27,000 cases are diagnosed annually, with a median age of 66 years at time of diagnosis.
“It’s considered an aggressive lymphoma which means that there’s pretty rapid tumor growth, but overall, it is curable,” Dr. Khurana said, noting that the initial treatment for the disease is R‑CHOP chemotherapy, the standard of care since at least 2008.
Upfront, about 80%-90% of patients respond to R-CHOP—a combination of chemotherapy medications, prednisone, and a monoclonal or protein antibody—given intravenously once every 3 weeks. But at least a third of patients with DLBCL relapse, meaning that R-CHOP cures perhaps only 60% of those with the disease.
“What we as clinicians and investigators over the last 15-20 years have tried to do is improve upon this R‑CHOP chemotherapy by trying different strategies and interventions, which includes either adding a novel therapy or adding any kind of targeted therapy to R‑CHOP, or intensifying the R‑CHOP treatment in itself,” Dr. Khurana said.
The problem, she said, is that “over the last 3 decades, we’ve noticed that the eligibility criteria for clinical trials have increased in number, and we’ve become pretty restrictive overall in the kind of people that we enroll in clinical trials.”
The irony is that although Black and Hispanic patients are far less likely to develop DLBCL, when they do, they get it at a much younger age, Dr. Khurana said, “and they present with much higher-risk disease and much more adverse disease, which is more likely to have recurrences or relapses.”
Disease Traits May Lead to Trial Exclusion
The study drew on the Mayo Clinic’s Lymphoma Epidemiology of Outcomes (LEO) cohort, which follows 2185 patients with lymphoma from 8 large US academic medical centers, including the Mayo Clinic. About 76% of those included in the sample were non-Hispanic White patients and 24% were Hispanic and/or non-White.
Several conclusions were noteworthy. Among them: White patients were diagnosed with DLBCL at an average age of 65 years, compared to 56 for Hispanic patients and 51 years for Black patients. Meanwhile, only 31% of White patients had B symptoms, compared to 37% of Hispanic patients and 44% of Black patients.
In addition, 28% of Black patients had hemoglobin levels of less than 10g/dL, compared to 19% of Hispanic patients and 13% of White patients. Black patients had the highest overall DLBCL trial exclusion rates, even though they were younger and had better kidney function than White patients.
“As a result, Hispanic and non-White patients were more likely to be ineligible for trials based on these lab values,” Maurer said in his presentation.
“These are the patients that we should be including in clinical trials, yet because these patients have adverse disease or high‑risk disease, what we also found in our study was that they’re presenting with way more lab abnormalities,” Dr. Khurana said. “If the disease itself is making us exclude these patients from trials, then we need to do something different.”
Dr. Khurana added that “as clinicians and clinical investigators, we need to make sure our trials are more representative of the general population, and to design smarter trials that allow for optimization of these patients before we enroll them.”
She also praised the American Society of Clinical Oncology (ASCO) for working with the US Food and Drug Administration (FDA) to come up with specific recommendations for clinical investigators to make these trials more inclusive.
“There’s a lot of awareness, and steps are being taken in the right direction,” she said. “I’m very hopeful that we are going to make a difference.”
“This work reinforces that many health outcomes are attached to the history of our nation and the social constructs that we deal with in the world,” said Chancellor Donald, MD, of Tulane University School of Medicine, New Orleans, Louisiana, who moderated a press briefing on the study at the ASH meeting.
“We consistently find that there’s work to be done, and researchers should continue not only to assess whether disparities exist, but to find opportunities to correct any disparities that they find.”