New research by Dr Elizabeth Goodall 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.
Dr Goodall, a practising haematologist, frequently treats patients with rDLBCL, an aggressive form of blood cancer. She has observed that real-world patients treated with novel therapies often experience poorer responses and greater toxicity than reported in clinical trials. Her research aimed to understand why outcomes in routine practice are different from those seen in trials, and whether clinical trial populations differ too greatly from the patients encountered in everyday care.
Her study examined the eligibility criteria of seven recent landmark rDLBCL clinical trials that led to the approval of new cancer drugs, including targeted treatments and CAR-T therapy.
Dr Goodall compared 180 Australian rDLBCL patients treated in standard clinical practice with a total of 320 episodes of relapse against the clinical trial criteria.
The findings were surprising in their magnitude and provided some clarity on why the patients enrolled in the trials had such differing profiles from those in the clinic.
- The seven included trials had a median of 39 eligibility criteria. When this large number of criteria was compared across the trials, there was also marked variability and discordance across criteria pertaining to both patient and disease domains. The greatest variation was seen in requirements relating to prior lines of therapy, definitions of measurable disease and organ function.
- Among the 320 relapse episodes included in the study, more than half (52%) were ineligible for all seven trials, and no patient met eligibility criteria for all seven studies. This means that had these patients been considered for the included trials, the majority would have been excluded from the very trials informing their treatment.
The findings therefore highlight a major challenge in lymphoma care: outcomes reported in clinical trials are frequently extrapolated to broader real-world populations who would not have qualified for those studies. This mismatch may help explain why patients treated in routine practice often experience poorer outcomes and worse toxicity than what is reported in trials.
rDLBCL clinical trials use strict and highly variable eligibility criteria that exclude most real-world patients. This severely limits clinicians’ ability to apply trial data to their own patients.
The study findings support the need for less restrictive and harmonised eligibility frameworks across trials and the need for real-world data to be integrated early in drug development to ensure future therapies deliver meaningful benefit to the populations most likely to receive them.
The study was published in the British Journal of Haematology. Dr Goodall is doing her PhD in the Lymphoma Clinical Innovations Laboratory at the Olivia Newton-John Cancer Research Institute, led by Prof Eliza Hawkes.