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ABSTRACTIntroduction: Selinexor is a first-in-class, oral therapeutic that selectively inhibits nuclear export. It has received fast track designation from the FDA for the treatment of relapsed or refractory diffuse large B-cell lymphoma (DLBCL) recently, and continues to be evaluated as a potential treatment for DLBCL.Area covered: This article reviews the available data from clinical trials regarding the efficacy of selinexor in DLBCL and highlights the key toxicity issues and how they may best be managed. Ongoing and future studies in DLBCL are also discussed.Expert opinion: More translational studies are necessary to leverage the unique mechanism action and rationally inform the use of selinexor in combination strategies. There are several different genetic subtypes of DLBCL, but it is not clear if these classifications will identify patients that may benefit from targeted therapies. The broad potential mechanism of action of selinexor will require careful analysis to inform predictive or prognostic biomarkers. Further evaluation of selinexor in combination with standard lymphoma regimens could identify deliverable promising regimens. Future randomized trials are key for registration and to determine the optimal role for this first-in-class agent.