Older adults (OA) with DLBCL are a heterogenous population with suboptimal outcomes. In this review, we identify and address the unique challenges encountered in the care of OA with DLBCL. We elaborate on the role and limitations of current geriatric assessment (GA) tools and ways to incorporate fitness in therapeutic decision making. We suggest best practices to implement GA in routine practice and clinical trials. The most widely used tool is simplified GA (sGA) which categorizes patients into fit, unfit and frail groups. Patients who are fit benefit from full dose/curative approach, whereas consideration should be made to reduce the intensity of chemotherapy for unfit patients. Frail patients with DLBCL are a major unmet need without any satisfactory treatment options. Ongoing investigations combining novel therapies into chemotherapy-free regimens are underway with promising early results. In the relapsed/refractory (R/R) setting, anti-CD19 CAR-T cell therapy (CART) is now the standard of care for primary refractory disease or relapse within 12 months of completing therapy. Autologous stem cell transplant is still a consideration for fit OA with relapse >12 months after completing therapy. The recent approval of bispecific antibodies is a welcome advance that will greatly benefit OA not eligible for CART. Other regimens available for patients ineligible for CART or for those who experience progression post-CART include polatuzumab-rituximab±bendamustine, tafasitamab-lenalidomide, loncastuximab or chemotherapy-based approaches such as rituximab-gemcitabine-oxaliplatin. We discuss the changing paradigm in R/R DLBCL and spotlight emerging data from recent congresses that can improve outcomes in this vulnerable population.
