Older patients with lymphoma: navigating a landscape of clinical controversies and barriers to innovation

Older patients with lymphoma represent a growing, heterogeneous population whose care is challenged by diverse outcomes, limited evidence, and one-dimensional age definitions. Historically, arbitrary age thresholds such as ≥60 or ≥80 years have guided treatment decisions, yet they fail to capture the biological and functional diversity of aging and can limit opportunities for cure and progress. Current practice relies on arbitrary dose reductions in old age, such as RminiCHOP, despite limited data for optimal intensity and benefit-risk trade-offs. Likewise, novel agents and combination therapies frequently demonstrate discrepant efficacy and safety across age groups, but systematic attempts to optimize dose for the older patients are rarely prioritized. When it comes to clinical trials, documenting benefit of new therapies is more challenging in older patients due to high background mortality that complicates interpretation of overall and progression-free survival and may led to underpowered trials. Moreover, prognostic models developed in younger populations have limited applicability in older patients, as they overlook the broader range of clinically relevant outcomes in older patients, including treatment-related mortality, functional decline, and quality of life. Pre-therapeutic geriatric assessments are prognostic, but their predictive capability remains to be demonstrated in prospective trials before use as treatment decision support tools. Addressing these challenges requires reframing of "old age" to a multidimensional construct, incorporating geriatric assessment, patient preferences, and biological age. More inclusive trial designs, dedicated dose-finding in older patients, and development of holistic, predictive models are critical to advance care. Without this, progress risks stalling for a growing group of our patients.