Diffuse Large B Cell Lymphoma: Changing Landscapes of Treatment Strategy and the Aspirations in 2024

Diffuse large B-cell lymphoma (DLBCL) represents the commonest subtype of non-Hodgkin lymphoma, encompasses a group of diverse disease entities, each harbouring unique molecular and clinico-pathological feature. The understanding of the molecular landscape of DLBCL has improved significantly over the past decade, highlighting unique genomic subtypes with implications on targeted therapy. At the same time, several new treatment modalities have been recently approved both in the frontline and relapsed settings, ending a dearth of negative clinical trials that plagued the past decade. Despite that, in the real-world setting, issues like drug accessibility, reimbursement policies, physician and patient preference, as well as questions regarding optimal sequencing of treatment options present difficulties and challenges in day-to-day haemato-oncology practice. Here, we review the recent advances in the therapeutic armamentarium of DLBCL and discuss implications on the practice landscape. Diffuse large B-cell lymphoma (DLBCL) is usually treated with chemoimmunotherapy in curative intention at initial diagnosis. Novel agents have improved the prognosis of high-risk patients in the front-line and relapsed setting and more accurate prognostic tools enable less intensive treatment for low-risk patients, while maintaining their good prognosis. Here, we summarise our approach to DLBCL patients in the first line setting according to their risk profile and other common challenges in clinical practice. We recommend an abbreviated course of chemoimmunotherapy in low-risk patients and a negative interim positron emission tomography. For patients with higher-risk disease, a new combination treatment with polatuzumab vedotin has been approved and is a new option in these patients. We also discuss our approach to patients with high risk for subsequent central nervous system involvement, with leg-type lymphoma or with severe comorbidities which we encounter frequently in our daily clinical practices.