Despite the curative potential of frontline therapy in diffuse large B-cell lymphoma (DLBCL), nearly a third of patients will have relapsed or refractory disease and thus have a poor prognosis. While potentially curative options exist in the relapsed setting, these treatments are intensive, are not available to all patients, and are associated with high rates of relapse. As such, there is considerable interest in preemptively identifying high-risk patients who could benefit from modifications to initial treatment strategies. Alternatively, there may also be a subset of patients with favorable disease who could benefit from de-escalation strategies and reduction in toxicity. Personalized treatment approaches, including those that incorporate modification of therapy based on early response assessments, have the potential to improve outcomes in DLBCL, though these approaches require further evaluation in clinical practice. Here we review the prognostic role of interim positron emission tomography and the primarily unsuccessful efforts to use this tool to guide response-adaptive treatment strategies thus far. We subsequently review the potential role of evaluating minimal residual disease (MRD) in this context, discussing the available tools, the data to support its role in interim response assessment, and the future directions of MRD use in DLBCL clinical trials.

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