HMN 2026: How Real-world lymphoma patients are often excluded from trials shaping their treatment

A new study has uncovered why many patients with relapsed diffuse large B-cell lymphoma (rDLBCL) fail to respond as well as expected to newly approved cancer therapies. Patients treated with novel therapies in routine practice often experience poorer responses and greater toxicity than those reported in clinical trials.

Researchers at the Olivia Newton-John Cancer Research Institute (ONJCRI) compared 180 patients with rDLBCL against the eligibility criteria of seven recent landmark clinical trials that led to the approval of new therapies, including targeted treatments and CAR-T therapy.

The research was published in the Leukemia & Lymphoma.

The study findings were surprising in their magnitude, as the patient populations enrolled in these trials differed substantially from real-world patients.

Across the 320 relapse episodes recorded in the 180 patients, more than half (52%) were ineligible for any trial, and no patient was eligible for all seven.

The researchers pointed out that it is common practice to extrapolate clinical trial outcome data to broader patient groups; however, this is likely to include those same patients who would not have qualified for the very trials informing their therapy in the clinic.

The trials required patients to meet a median of 39 eligibility criteria, many of which were highly variable and inconsistent between the seven studies.

The greatest differences related to prior treatment, definitions of measurable disease, and organ function requirements.

Practicing hematologist and lead researcher, Dr. Elizabeth Goodall, says, “This supports the hematology community’s concerns that clinical trial cohorts and real-world cohorts are really very different.”

“Only the ‘best’ patients are eligible for these clinical trials, and once the treatment has been approved by the regulatory bodies, there is far less regulation over which patients receive the treatment in the clinics. This can expose patients to unexpected toxicity and lower than expected treatment efficacy.

“We recognize that early-stage trials require robust eligibility criteria to ensure patient safety. However, registrational trials should really adopt more inclusive and permissive criteria to better reflect the characteristics of real-world populations.”

The research team encourages clinicians treating patients with lymphoma to carefully consider the eligibility criteria of the clinical trials that secured therapy approvals when interpreting efficacy and safety outcomes, and when counseling patients about expected treatment benefits and risks.

Over 26,000 Australians are living with one of the 80+ subtypes of lymphoma, the most common type of blood cancer nationally.

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