Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and remains curable for many patients with frontline immunochemotherapy; however, optimal treatment continues to evolve. The Canadian Hematology Consensus Group convened a national panel of lymphoma experts to develop evidence-informed recommendations for the first-line management of adults with DLBCL in Canada. Recommendations were developed using a modified Delphi process and address frontline regimen selection, treatment intensity, central nervous system (CNS) risk assessment and prophylaxis, interim response assessment, and end of treatment management. The panel recommends Pola-R-CHP for patients with international prognostic index 2–5 and activated B-cell subtype by gene expression profiling (or if unavailable, non-germinal centre B-cell subtype by immunohistochemistry). All patients should be assessed for fitness to receive full-dose therapy, with dose attenuation considered when clinically appropriate. Routine high-dose methotrexate prophylaxis is not recommended, and CNS screening should be individualized. Interim imaging may be used to confirm response, but treatment escalation should not be based on PET positivity alone. Patients achieving complete metabolic response at end of treatment require no further therapy, and routine surveillance imaging is not recommended. These recommendations support consistent, evidence-informed, and equitable care for patients with newly diagnosed DLBCL across Canada.
