Trial for Patients 75 and Older with Diffuse Large B-Cell Lymphoma Helps Address Care Inequities

Diffuse large B-cell lymphoma (DLBCL) is curable in roughly 60% of cases, yet an estimated 10-15% of patients 80+ years old with the disease receive no treatment, due to concerns about tolerance to the combination of rituximab, cyclophosphamide, doxorubicin, vincristine and prednisone (R-CHOP) that is standard of care for younger patients. To address this issue, Cleveland Clinic has joined a phase 2/3 National Cancer Institute (NCI) trial investigating treatment options specifically for older patients.

This nationwide trial is studying the safety and efficacy of using reduced doses of CHOP chemotherapy and standard doses of rituximab (“R-mini-CHOP”) compared to the same combination with the addition of the oral chemotherapy azacitidine (“R-mini-CHOP + aza”).

Study background

Nearly one third of patients with DLBCL are 75 years or older – an age group that is severely under-represented in cancer clinical trials. Although older adults make up more than 40 percent of the overall population with cancer, fewer than 10% of patients in this age group participate in NCI-sponsored clinical trials.

This is due to a number of factors, including:

• Trial criteria that excludes older patients and/or those with comorbidities
• Barriers such as transportation issues that can disproportionately impact older patients
• Misconceptions among physicians and others about older patients’ willingness to participate in trials

Despite FDA guidance on enrolling older adults in cancer studies and calls in the medical community to broaden eligibility criteria, age disparities persist.

“Older patients are not frequently studied but this is a large portion of people who need improved outcomes and it makes sense to prioritize this study,” says Allison Winter, MD, an oncology and hematology specialist at Cleveland Clinic’s Taussig Cancer Center and a collaborator on the NCI trial.

Room for improvement in treating older patients

A previous phase 2 trial of full-dose rituximab and reduced-dose CHOP in older patients with DLBCL found a two-year progression-free survival of 47% and a two-year overall survival of 59%. “That is definitely less than we would expect in younger populations, which shows there is room for improvement,” says Dr. Winter.

The next step is to study whether the addition of azacitidine to this regimen improves efficacy and is well tolerated. “Azacitidine is already used to treat older patients with myelodysplastic syndrome and acute leukemia, so we know that it is tolerated in and there’s also scientific rationale for why it might be helpful in patients with diffuse large B-cell lymphoma.”

Eligibility criteria

Newly diagnosed patients with DLBCL who are age 75 or greater with a performance or ECOG status of 0-2 may be eligible for the study. Patients with grade 3B follicular lymphoma, high-grade B-cell lymphomas with MYC and BCL2 and/or BCL6 rearrangements may also be eligible.

Often comorbidities such as coronary artery disease, renal disease and diabetes automatically exclude patients from trials, but that is not the case in this instance. Patients with comorbidities are still eligible, with the exception of those with active cardiac disease within 26 weeks prior to trial registration. See clinicaltrials.gov for additional eligibility criteria.

Referring physicians are encouraged to reach out for a virtual or in-person consult if they have a patient who may be eligible for the trial.

Study details

Study participants are randomized to one of two arms (R-mini-CHOP or R-mini-CHOP + aza), receiving the given treatment for up to six cycles in the absence of disease progression or unacceptable toxicity. After completion of study treatment, patients will be followed periodically up to five years from the date of trial registration. The trial has completed the safety run in phase 1 and is enrolling into the phase 2 portion of the trial. There are already 69 patients enrolled. This study is open at many other cancer centers around the country.

Making trials more convenient

To improve accessibility, Cleveland Clinic is making it possible for patients to participate in the trial at the main campus or at one of the below locations across Ohio.

• Fairview
• Hillcrest
• Independence
• Mansfield
• Sandusky
• South Pointe
• Strongville
• Wooster

Patients who have issues getting to/from clinic appointments can connect with a social worker who can provide transportation and other supportive services.

Ultimately, the investigators hope the insights gained through the study will help to broaden their understanding and ability to treat older populations facing DLBCL and similar diseases.