News release

From: Olivia Newton-John Cancer Research Institute

Expectation vs reality: research finds real-world lymphoma patients often excluded from trials shaping their treatment

MELBOURNE: 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.[1]

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 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.

Practising haematologist and lead researcher, Dr Elizabeth Goodall, says: “This supports the haematology 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 recognise 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 counselling 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.[2]

The research was published in the British Journal of Haematology.

[1] https://www.tandfonline.com/doi/full/10.1080/10428194.2024.2371472

[2] https://www.canceraustralia.gov.au/cancer-types/lymphoma/lymphoma-australia-statistics

ENDS

Publication available at: https://doi.org/10.1111/bjh.70550

Available for interview: Dr Elizabeth Goodall, researcher at ONJCRI

NOTES

About the Olivia Newton-John Cancer Research Institute (ONJCRI)

ONJCRI is a global leader in advancing cancer research, driven by the singular goal of improving patient outcomes. We drive progress by discovering and developing diagnostics and therapeutics that are more effective, tolerable, and accessible. ONJCRI adopts a tumour-agnostic approach, targeting shared pathways across multiple cancer types. This innovative strategy enables us to deliver scalable and impactful therapies that benefit diverse patient populations, accelerating progress across the entire landscape.

By bridging laboratory discoveries and clinical applications, ONJCRI is redefining how cancer treatments are designed and delivered: from bedside to bench to bedside. With a steadfast commitment to equity, innovation, and collaboration, we strive to transform cancer care, addressing unmet needs and overcoming disparities in access for all communities. For more about the Olivia Newton-John Cancer Research Institute, visit www.onjcri.org.au.

ONJCRI is an independent medical research institute and is affiliated with La Trobe University as the School of Cancer Medicine.