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.
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The writing of this manuscript was supported by Genome Canada, the Ontario Research Fund, the Leukemia & Lymphoma Society of Canada, the Princess Margaret Cancer Centre and the Princess Margaret Cancer Foundation. Preparation of the figures was aided with BioRender.com.
Conflict of interest
MYH declares no conflict of interest. RK reports research funding from Gilead Sciences and Roche.
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He, M.Y., Kridel, R. Treatment resistance in diffuse large B-cell lymphoma. Leukemia 35, 2151–2165 (2021). https://doi.org/10.1038/s41375-021-01285-3