Treatment resistance in diffuse large B-cell lymphoma

Diffuse large B-cell lymphoma (DLBCL) is a highly heterogeneous disease and represents the most common subtype of lymphoma. Although 60-70% of all patients can be cured by the current standard of care in the frontline setting, the majority of the remaining patients will experience treatment resistance and have a poor clinical outcome. Numerous efforts have been made to improve the efficacy of the standard regimen by, for example, dose intensification or adding novel agents. However, these results generally failed to demonstrate significant clinical benefits. Hence, understanding treatment resistance is a pressing need to optimize the outcome of those patients. In this Review, we first describe the conceptual sources of treatment resistance in DLBCL and then provide detailed and up-to-date molecular insight into the mechanisms of resistance to the current treatment options in DLBCL. We lastly highlight the potential strategies for rationally managing treatment resistance from both the preventive and interventional perspectives.