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Purpose: Selinexor is a first-in-class, oral selective-inhibitor-of-nuclear-export, granted accelerated approval by FDA (2019) for relapsed and refractory multiple myeloma (RRMM). We sought to quantitatively summarize the selinexor efficacy and safety in RRMM., Methods: We searched PubMed, EMBASE, CENTRAL, clinicaltrial.gov, and google scholar, until May 2023, studies about selinexor use in RRMM. The outcome measures of interest were primarily efficacy outcomes, in addition to safety outcomes. Random-effect model analyses were performed, at statistical significance of P<0.05, using the RevMan software., Results: Meta-analyses of eleven included clinical trials yielded a significant 56.21% overall clinical benefit, 46.91% overall response, 4.89% complete response, 23.41% very good partial response, 24.68% partial response, and 28.06% stable disease rates with selinexor. Due to safety reasons, selinexor caused significant increase in discontinuation rate, 16.80%. Subgroup analyses demonstrated higher efficacy with selinexor plus dexamethasone and proteasome inhibitor combinations than with selinexor alone. The multiple myeloma type, high cytogenetic risk, refractory state, and advanced disease state did not affect performance. Risk of selection, performance, and detection biases were unclear in the included trials., Conclusion: Selinexor led to significant positive responses with an acceptable safety profile in RRMM patients, despite higher rates of safety-related discontinuations. Selinexor-based combinations further enhanced response., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Inc.)

Purpose: Selinexor is a novel XPO1 inhibitor which inhibits the export of tumor suppressor proteins and oncoprotein mRNAs, leading to cell-cycle arrest and apoptosis in cancer cells. While selinexor is currently FDA approved to treat multiple myeloma, compelling preclinical and early clinical studies reveal selinexor's efficacy in treating hematologic and non-hematologic malignancies, including sarcoma, gastric, bladder, prostate, breast, ovarian, skin, lung, and brain cancers. Current reviews of selinexor primarily highlight its use in hematologic malignancies; however, this review seeks to summarize the recent evidence of selinexor treatment in solid tumors., Methods: Pertinent literature searches in PubMed and the Karyopharm Therapeutics website for selinexor and non-hematologic malignancies preclinical and clinical trials., Results: This review provides evidence that selinexor is a promising agent used alone or in combination with other anticancer medications in non-hematologic malignancies., Conclusion: Further clinical investigation of selinexor treatment for solid malignancies is warranted., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Despite a number of treatment options, patients with diffuse large B-cell lymphoma (DLBCL) whose disease has become refractory to treatment have a poor prognosis. Selinexor is a novel, oral drug that is approved to treat patients with relapsed/refractory DLBCL. In this post hoc analysis of the SADAL study, a multinational, open-label study, we evaluated subpopulations to determine if response to single agent selinexor is impacted by number of lines of prior treatment, autologous stem cell transplant (ASCT), response to first and most recent therapies, and time to progressive disease., Patients: Patients (n = 134) with DLBCL after 2-5 prior therapies were enrolled in SADAL and received 60mg selinexor twice weekly., Results: The median overall survival was 9.0 months and median progression free survival was 2.6 months. Patients who had the best overall response rate (ORR) and disease control rate were those who had prior ASCT (42.5% and 50.0%) or responded to last line of therapy (35.9% and 43.5%). Patients with primary refractory DLBCL also showed responses (ORR 21.8%). Adverse events between subgroups were similar to the overall study population, the most common being thrombocytopenia (29.1%), fatigue (7.5%), and nausea (6.0%)., Conclusion: Regardless of prior therapy and disease refractory status, selinexor treatment demonstrated results consistent with its novel mechanism of action and lack of cross-resistance. Thus, single agent oral selinexor can induce deep, durable, and tolerable responses in patients with DLBCL who have recurrent disease after several chemoimmunotherapy combination regimens., (Copyright © 2021. Published by Elsevier Inc.)

Overexpression of Exportin-1 ( XPO1 ), a key regulator of nuclear-to-cytoplasmic transport, is associated with inferior patient outcomes across a range of adult malignancies. Targeting XPO1 with selinexor has demonstrated promising results in clinical trials, leading to FDA approval of its use for multiple relapsed/refractory cancers. However, XPO1 biology and selinexor sensitivity in childhood cancer is only recently being explored. In this review, we will focus on the differential biology of childhood and adult cancers as it relates to XPO1 and key cargo proteins. We will further explore the current state of pre-clinical and clinical development of XPO1 inhibitors in childhood cancers. Finally, we will outline potentially promising future therapeutic strategies for, as well as potential challenges to, integrating XPO1 inhibition to improve outcomes for children with cancer.