Challenging the Status Quo on Lymphoma Research Endpoints: Results from a Global Stakeholder Survey

Background: Heterogeneity in stakeholder priorities for lymphoma clinical trial endpoints complicates therapeutic evaluation and regulatory decision-making. While survival metrics dominate for aggressive lymphoma research, indolent lymphomas, which have prolonged survival, require endpoints reflecting chronic disease management. This study examined global stakeholder consensus on clinical endpoints, patient-reported outcomes (PROs), and efficacy measures to inform endpoint harmonisation in lymphoma research. <div> <br> </div> <div> Methods: For this cross-sectional international survey (February–March 2025), 133 stakeholders rated the importance of clinical endpoints (established and surrogate endpoints) and PROs. Data from all respondents were divided into four subgroups: people with lived experience (PWLE; patients and care partners), healthcare professionals, researchers, and other contributors (e.g., industry professionals). Subgroup priorities were analysed with descriptive statistics, complemented by thematic analysis of open-ended survey responses. <div> <br> </div> <div> Findings: Overall survival (OS) and progression-free survival were universally endorsed as primary and key endpoints (&gt;92% of all subgroups rated them as important or very important for evaluating treatment efficacy). Priorities diverged for other endpoints. PWLE prioritised health-related quality of life (HRQoL; 96·8% versus 80·0% other contributors). For indolent lymphomas, HRQoL (73%) and time-to-next-treatment (72%) surpassed OS relevance for all respondents. Respondents recognised the challenges of MRD, such as validation gaps and subtype-specific utility (e.g., robust in mantle cell lymphoma, limited in marginal zone lymphoma). </div> <div> <br> </div> <div> Interpretation: Endpoint selection must balance survival metrics with PROs, particularly for indolent lymphomas. We advocate for HRQoL to be incorporated as a key endpoint (primary or secondary, as appropriate) and for PRO data to be collected rigorously and proportionately to the trial objectives, in all studies for which these measures can meaningfully inform clinical and regulatory decision-making. Regulatory alignment will enhance therapeutic relevance. </div> </div>