Management of diffuse large B‑cell lymphoma in older adults: current strategies and emerging directions

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma in older adults. Treatment in this population remains challenging due to heightened genetic heterogeneity and reduced physiological reserve, which increase susceptibility to both treatment-related toxicity and the risk of undertreatment. Comprehensive geriatric assessment is essential to categorize patients as fit, unfit, or frail, enabling individualized therapeutic strategies. Fit patients benefit from standard R-CHOP or Pola-R-CHP regimens, while unfit patients are suitable for dose-reduced regimens. Anthracycline-containing therapy is recommended when feasible; alternatives such as etoposide or gemcitabine may be used when anthracyclines are contraindicated. Frail patients lack standardized treatment protocols, presenting a significant clinical dilemma; however, advances in geriatric assessment tools and novel therapies are expected to shift the management paradigms from purely palliative care to curative‑intent strategies. Current geriatric assessment tools have limitations, and the distinction between unfit and frail remains fluid. Dynamic fitness assessment and pre-phase treatment strategies may enable some patients to “improve” to a higher fitness level. Emerging evidence supports the efficacy of novel targeted agents, including small-molecule inhibitors, bispecific antibodies, and antibody-drug conjugates, which are reshaping first-line treatment paradigms. Nevertheless, their implementation in community settings faces substantial practical barriers, such as the need for cytokine release syndrome monitoring, caregiver burden, financial toxicity, and adherence challenges. This review provides a comprehensive overview of current strategies and emerging directions for managing older adults with DLBCL.