Marked variation in eligibility criteria across registrational trials for relapsed diffuse large B-cell lymphoma...

Therapeutic options for relapsed or refractory diffuse large B-cell lymphoma (rDLBCL) have expanded following accelerated approvals based largely on surrogate end-points, yet confirmatory studies have not consistently reproduced these benefits across all agents, and outcomes for many patients remain poor. Restrictive and heterogeneous eligibility criteria further limit generalisability of trial findings to routine populations. We examined eligibility criteria across seven registrational rDLBCL trials and applied them hypothetically to a real-world cohort of 180 patients treated in Australia with standard-of-care therapies. The trials required a median of 39 criteria (range 31-45), with marked variability across patient and disease domains. The greatest discordance related to prior lines of therapy, definitions of measurable disease and organ function parameters. Among 320 patient relapses (median 1, range 1-8), 52% were ineligible for any trial and no patient met criteria for all seven. Eligibility ranged from 4% (SADAL) to 22% (ZUMA-1). Common reasons for exclusion were limits on prior therapy, washout requirements and organ dysfunction. Overall survival did not differ between patients ineligible for all trials and those eligible for at least one (p = 0.97). Median progression-free survival (PFS) was comparable to registrational studies in both groups. Substantial eligibility heterogeneity excludes most real-world patients, limiting trial generalisability and supporting the need for more inclusive, standardised frameworks.