{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:53:18Z","timestamp":1791366798599,"version":"4.3.1"},"reference-count":60,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:00:00Z","timestamp":1791244800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>The treatment of relapsed\/refractory multiple myeloma (RRMM) remains a significant clinical challenge, particularly for patients with multidrug resistance, who have a poor prognosis and limited therapeutic options. Selinexor, as the world's first oral selective inhibitor of nuclear export (SINE), targets the XPO1 protein, offering a novel treatment mechanism distinct from traditional agents for RRMM. This narrative review systematically synthesizes the mechanism of action of Selinexor and critically evaluates evidence from key clinical studies (such as the STORM and BOSTON trials). It focuses on discussing its clinical positioning across different scenarios and its combination strategies with commonly used regimens (e.g., SVd). It also addresses standardized, proactive management pathways for its characteristic adverse effects (e.g., thrombocytopenia, gastrointestinal reactions). These strategies are tailored to patient stratification (such as triple-\/penta-refractory, elderly\/frail patients). The aim is to provide clinicians with a practical, evidence-based reference for the safe and effective application of this drug to optimize treatment outcomes for RRMM patients.<\/jats:p>","DOI":"10.3389\/fmed.2026.1927209","type":"journal-article","created":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:20:48Z","timestamp":1791364848000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy analysis and adverse event management of selinexor in the treatment of relapsed\/refractory multiple myeloma"],"prefix":"10.3389","volume":"13","author":[{"given":"Zengli","family":"Kuang","sequence":"first","affiliation":[{"name":"Weifang People's Hospital, Shandong Second Medical University, Not applicable Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Chen","sequence":"additional","affiliation":[{"name":"Weifang People's Hospital, Shandong Second Medical University, Not applicable Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cuiai","family":"Ren","sequence":"additional","affiliation":[{"name":"Weifang People's Hospital, Shandong Second Medical University, Not applicable Weifang","place":["Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,10,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"575","DOI":"10.2174\/1871520620666200918113625","article-title":"Anti-cancer activity of curcumin on multiple myeloma","volume":"21","author":"Mirzaei","year":"2021","journal-title":"Anticancer Agents Med Chem"},{"key":"B2","doi-asserted-by":"publisher","first-page":"62","DOI":"10.1002\/hon.2586","article-title":"Multiple myeloma: every year a new standard?","volume":"37","author":"Rajkumar","year":"2019","journal-title":"Hematol Oncol"},{"key":"B3","doi-asserted-by":"publisher","first-page":"464","DOI":"10.1001\/jama.2022.0003","article-title":"Diagnosis and management of multiple myeloma: a review","volume":"327","author":"Cowan","year":"2022","journal-title":"JAMA"},{"key":"B4","first-page":"771","article-title":"Multiple myeloma over two decades: where do we go from here?","volume-title":"Chin J Biochem Mol Biol","author":"Liu","year":"2025"},{"key":"B5","doi-asserted-by":"publisher","first-page":"e670","DOI":"10.1016\/S2352-3026(22)00165-X","article-title":"The epidemiological landscape of multiple myeloma: a global cancer registry estimate of disease burden, risk factors, and temporal trends","volume":"9","author":"Huang","year":"2022","journal-title":"Lancet Haematol"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1049","DOI":"10.1080\/14740338.2023.2274420","article-title":"A safety review of recently approved and emerging drugs for patients with relapsed or refractory multiple myeloma","volume":"22","author":"Midha","year":"2023","journal-title":"Expert Opin Drug Saf"},{"key":"B7","doi-asserted-by":"publisher","first-page":"2516","DOI":"10.1182\/blood-2007-10-116129","article-title":"Improved survival in multiple myeloma and the impact of novel therapies","volume":"111","author":"Kumar","year":"2008","journal-title":"Blood"},{"key":"B8","doi-asserted-by":"publisher","first-page":"703","DOI":"10.20892\/j.issn.2095-3941.2024.0177","article-title":"Multiple myeloma survival in New South Wales, Australia, by treatment era to 2020","volume":"21","author":"Feletto","year":"2024","journal-title":"Cancer Biol Med"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1655","DOI":"10.3390\/jcm14051655","article-title":"Current treatment strategies for multiple myeloma at first relapse","volume":"14","author":"Mavrothalassitis","year":"2025","journal-title":"J Clin Med"},{"key":"B10","doi-asserted-by":"publisher","first-page":"104913","DOI":"10.1016\/j.critrevonc.2025.104913","article-title":"Next-generation immunotherapy in relapsed\/refractory multiple myeloma: strategies to achieve sustained MRD negativity","volume":"214","author":"Zhu","year":"2025","journal-title":"Crit Rev Oncol Hematol"},{"key":"B11","doi-asserted-by":"publisher","first-page":"525","DOI":"10.3390\/cancers17030525","article-title":"The evolving landscape in multiple myeloma: from risk stratification to T cell-directed advanced therapies","volume":"17","author":"Besliu","year":"2025","journal-title":"Cancers (Basel)"},{"key":"B12","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1038\/s41571-020-00442-4","article-title":"The nuclear export protein XPO1 \u2013 from biology to targeted therapy","volume":"18","author":"Azmi","year":"2021","journal-title":"Nat Rev Clin Oncol"},{"key":"B13","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1016\/j.clml.2018.03.003","article-title":"Clinical implications of targeting XPO1-mediated nuclear export in multiple myeloma","volume":"18","author":"Gandhi","year":"2018","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B14","doi-asserted-by":"publisher","first-page":"459","DOI":"10.3390\/ddc2020023","article-title":"Selinexor and other selective inhibitors of nuclear export (SINEs)\u2014a novel approach to target hematologic malignancies and solid tumors","volume":"2","author":"Karaszewski","year":"2023","journal-title":"Drugs Drug Candidates"},{"key":"B15","doi-asserted-by":"publisher","first-page":"e105","DOI":"10.1016\/S1470-2045(20)30756-7","article-title":"Treatment of relapsed and refractory multiple myeloma: recommendations from the international myeloma working group","volume":"22","author":"Moreau","year":"2021","journal-title":"Lancet Oncol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"2266","DOI":"10.1038\/s41375-019-0435-7","article-title":"Outcomes of patients with multiple myeloma refractory to CD38-targeted monoclonal antibody therapy","volume":"33","author":"Gandhi","year":"2019","journal-title":"Leukemia"},{"key":"B17","doi-asserted-by":"publisher","first-page":"2997","DOI":"10.1038\/ncomms3997","article-title":"Heterogeneity of genomic evolution and mutational profiles in multiple myeloma","volume":"5","author":"Bolli","year":"2014","journal-title":"Nat Commun"},{"key":"B18","doi-asserted-by":"publisher","first-page":"445","DOI":"10.1200\/JCO.2011.37.8919","article-title":"The 39th david A. Karnofsky lecture: bench-to-bedside translation of targeted therapies in multiple myeloma","volume":"30","author":"Anderson","year":"2012","journal-title":"J Clin Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"732","DOI":"10.1016\/j.exphem.2015.04.010","article-title":"Novel therapeutic strategies for multiple myeloma","volume":"43","author":"Mimura","year":"2015","journal-title":"Exp Hematol"},{"key":"B20","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1182\/blood.2020007081","article-title":"Multiple cereblon genetic changes are associated with acquired resistance to lenalidomide or pomalidomide in multiple myeloma","volume":"137","author":"Gooding","year":"2021","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","first-page":"92","DOI":"10.1186\/s40364-025-00799-7","article-title":"Novel immunotargets in multiple myeloma: biological relevance and therapeutic potential","volume":"13","author":"Kotulov\u00e1","year":"2025","journal-title":"Biomark Res"},{"key":"B22","doi-asserted-by":"publisher","first-page":"58","DOI":"10.1053\/j.seminhematol.2024.12.001","article-title":"Advancements in bispecific antibodies for multiple myeloma: what\u2019s new and what lies ahead","volume":"62","author":"Mouhieddine","year":"2025","journal-title":"Semin Hematol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"4621","DOI":"10.1182\/blood-2012-05-429506","article-title":"Selective inhibitors of nuclear export show that CRM1\/XPO1 is a target in chronic lymphocytic leukemia","volume":"120","author":"Lapalombella","year":"2012","journal-title":"Blood"},{"key":"B24","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1038\/leu.2013.115","article-title":"CRM1 Inhibition induces tumor cell cytotoxicity and impairs osteoclastogenesis in multiple myeloma: molecular mechanisms and therapeutic implications","volume":"28","author":"Tai","year":"2014","journal-title":"Leukemia"},{"key":"B25","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/leu.2012.219","article-title":"Antileukemic activity of nuclear export inhibitors that spare normal hematopoietic cells","volume":"27","author":"Etchin","year":"2013","journal-title":"Leukemia"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1233","DOI":"10.19746\/j.cnki.issn.1009-2137.2025.04.046","article-title":"The application progress of selinexor in the treatment of relapsed and refractory multiple myeloma\u2014review","volume":"33","author":"Tong","year":"2025","journal-title":"Zhongguo Shi Yan Xue Ye Xue Za Zhi"},{"key":"B27","doi-asserted-by":"publisher","first-page":"6142","DOI":"10.1158\/1078-0432.CCR-15-2885","article-title":"XPO1 Inhibition using selinexor synergizes with chemotherapy in acute myeloid leukemia by targeting DNA repair and restoring topoisomerase II\u03b1 to the nucleus","volume":"22","author":"Ranganathan","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B28","doi-asserted-by":"publisher","first-page":"101448","DOI":"10.1016\/j.tranon.2022.101448","article-title":"The molecular mechanism and challenge of targeting XPO1 in treatment of relapsed and refractory myeloma","volume":"22","author":"Sellin","year":"2022","journal-title":"Transl Oncol"},{"key":"B29","doi-asserted-by":"publisher","first-page":"135","DOI":"10.2147\/ITT.S429402","article-title":"Selinexor synergistically promotes the antileukemia activity of venetoclax in acute myeloid leukemia by inhibiting glycolytic function and downregulating the expression of DNA replication genes","volume":"12","author":"Jiang","year":"2023","journal-title":"Immunotargets Ther"},{"key":"B30","doi-asserted-by":"publisher","first-page":"727","DOI":"10.1056\/NEJMoa1903455","article-title":"Oral selinexor-dexamethasone for triple-class refractory multiple myeloma","volume":"381","author":"Chari","year":"2019","journal-title":"N Engl J Med"},{"key":"B31","doi-asserted-by":"publisher","first-page":"242","DOI":"10.1111\/ejh.14223","article-title":"Impact of prior treatment on selinexor, bortezomib, dexamethasone outcomes in patients with relapsed\/refractory multiple myeloma: extended follow-up subgroup analysis of the BOSTON trial","volume":"113","author":"Mateos","year":"2024","journal-title":"Eur J Haematol"},{"key":"B32","doi-asserted-by":"publisher","first-page":"1210","DOI":"10.1093\/neuonc\/noae280","article-title":"Autophagy modulates glioblastoma cell sensitivity to selinexor-mediated XPO1 inhibition","volume":"27","author":"Tang","year":"2025","journal-title":"Neuro Oncol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"1002310","DOI":"10.37349\/etat.2025.1002310","article-title":"Modulation of anti-tumour immunity by XPO1 inhibitors","volume":"6","author":"Fisher","year":"2025","journal-title":"Explor Target Antitumor Ther"},{"key":"B34","doi-asserted-by":"publisher","first-page":"4071","DOI":"10.3390\/jcm14124071","article-title":"Focusing on selinexor for holding and bridging prior to CAR-T in relapsed\/refractory multiple myeloma","volume":"14","author":"Khouri","year":"2025","journal-title":"J Clin Med"},{"key":"B35","doi-asserted-by":"publisher","first-page":"20406207231219442","DOI":"10.1177\/20406207231219442","article-title":"Treatment of multiple myeloma with selinexor: a review","volume":"15","author":"Huang","year":"2024","journal-title":"Ther Adv Hematol"},{"key":"B36","doi-asserted-by":"publisher","first-page":"e70249","DOI":"10.1002\/cnr2.70249","article-title":"Therapeutic potential of venetoclax and selinexor in targeting hypoxia-induced vulnerabilities in multiple myeloma","volume":"8","author":"Okabe","year":"2025","journal-title":"Cancer Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"216486","DOI":"10.1016\/j.canlet.2023.216486","article-title":"RNA-binding protein hnRNPU regulates multiple myeloma resistance to selinexor","volume":"580","author":"Wang","year":"2024","journal-title":"Cancer Lett"},{"key":"B38","doi-asserted-by":"publisher","first-page":"3175","DOI":"10.1182\/blood-2016-11-750174","article-title":"Selective inhibition of nuclear export with selinexor in patients with non-hodgkin lymphoma","volume":"129","author":"Kuruvilla","year":"2017","journal-title":"Blood"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1563","DOI":"10.1016\/S0140-6736(20)32292-3","article-title":"Once-per-week selinexor, bortezomib, and dexamethasone versus twice-per-week bortezomib and dexamethasone in patients with multiple myeloma (BOSTON): a randomised, open-label, phase 3 trial","volume":"396","author":"Grosicki","year":"2020","journal-title":"Lancet"},{"key":"B40","doi-asserted-by":"publisher","first-page":"6611","DOI":"10.1182\/blood-2023-190030","article-title":"Active STAT3 prevents selinexor-induced caspase-independent apoptosis in multiple myeloma","volume":"142","author":"Mack","year":"2023","journal-title":"Blood"},{"key":"B41","doi-asserted-by":"publisher","first-page":"114305","DOI":"10.1016\/j.biopha.2023.114305","article-title":"E3 ubiquitin ligase ASB8 promotes selinexor-induced proteasomal degradation of XPO1","volume":"160","author":"Kwanten","year":"2023","journal-title":"Biomed Pharmacother"},{"key":"B42","doi-asserted-by":"publisher","first-page":"6102","DOI":"10.1182\/blood-2025-6102","article-title":"Upregulation of BCMA expression by selinexor","volume":"146","author":"Verbruggen","year":"2025","journal-title":"Blood"},{"key":"B43","doi-asserted-by":"publisher","first-page":"792","DOI":"10.1002\/jha2.709","article-title":"Selinexor: targeting a novel pathway in multiple myeloma","volume":"4","author":"Mo","year":"2023","journal-title":"EJHaem"},{"key":"B44","doi-asserted-by":"publisher","first-page":"2219","DOI":"10.3324\/haematol.2023.284089","article-title":"Selinexor, daratumumab, bortezomib and dexamethasone for the treatment of patients with relapsed or refractory multiple myeloma: results of the phase II, nonrandomized, multicenter GEM-SELIBORDARA study","volume":"109","author":"Gonz\u00e1lez-Calle","year":"2024","journal-title":"Haematologica"},{"key":"B45","doi-asserted-by":"publisher","first-page":"718","DOI":"10.1038\/s41416-021-01608-2","article-title":"Once weekly selinexor, carfilzomib and dexamethasone in carfilzomib non-refractory multiple myeloma patients","volume":"126","author":"Gasparetto","year":"2022","journal-title":"Br J Cancer"},{"key":"B46","doi-asserted-by":"publisher","first-page":"101076","DOI":"10.1016\/j.currproblcancer.2024.101076","article-title":"Efficacy and safety of selinexor for patients with relapsed and refractory multiple myeloma: a meta-analysis","volume":"50","author":"Shafei","year":"2024","journal-title":"Curr Probl Cancer"},{"key":"B47","doi-asserted-by":"publisher","first-page":"2187972","DOI":"10.1080\/16078454.2023.2187972","article-title":"Optimal timing and drug combination of selinexor in multiple myeloma: a systematic review and meta-analysis","volume":"28","author":"Gu","year":"2023","journal-title":"Hematology"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1649493","DOI":"10.3389\/fonc.2025.1649493","article-title":"Lower dose and weekly schedules of selinexor in multiple myeloma \u2013 updated evidence on safety and efficacy","volume":"15","author":"Baljevic","year":"2025","journal-title":"Front Oncol"},{"key":"B49","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1016\/j.clml.2023.07.013","article-title":"Real world efficacy and toxicity of selinexor: importance of patient characteristics, dose intensity and post progression outcomes","volume":"23","author":"Kastritis","year":"2023","journal-title":"Clin Lymphoma Myeloma Leuk"},{"key":"B50","doi-asserted-by":"publisher","first-page":"12600","DOI":"10.1182\/blood-2022-158060","article-title":"Real-World safety and effectiveness of selinexor-based regimens in patients with relapsed or refractory multiple myeloma and dialysis-dependent renal impairment","volume":"140","author":"Bentur","year":"2022","journal-title":"Blood"},{"key":"B51","doi-asserted-by":"publisher","first-page":"5991","DOI":"10.1038\/s41598-020-62885-0","article-title":"Concepts of double hit and triple hit disease in multiple myeloma, entity and prognostic significance","volume":"10","author":"Baysal","year":"2020","journal-title":"Sci Rep"},{"key":"B52","doi-asserted-by":"publisher","first-page":"384","DOI":"10.3390\/life14030384","article-title":"Efficacy of selinexor in relapsed\/refractory multiple myeloma (RRMM) patients with del17p and other high-risk abnormalities (A retrospective single-center study)","volume":"14","author":"Ehsan","year":"2024","journal-title":"Life (Basel)"},{"key":"B53","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1007\/s10238-025-01821-w","article-title":"Therapeutic options for extramedullary involvement in multiple myeloma","volume":"25","author":"Zhao","year":"2025","journal-title":"Clin Exp Med"},{"key":"B54","doi-asserted-by":"publisher","first-page":"28557","DOI":"10.1038\/s41598-024-79537-2","article-title":"Selinexor combined with bortezomib, lenalidomide, and dexamethasone for the treatment of newly diagnosed multiple myeloma with extramedullary disease","volume":"14","author":"Yin","year":"2024","journal-title":"Sci Rep"},{"key":"B55","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s13045-024-01565-2","article-title":"Impact of a best practices program in patients with relapsed\/refractory multiple myeloma receiving selinexor","volume":"17","author":"Bian","year":"2024","journal-title":"J Hematol Oncol"},{"key":"B56","doi-asserted-by":"publisher","first-page":"626","DOI":"10.1097\/01.HS9.0000846548.89204.ce","article-title":"Effectiveness and safety of selinexor-based regimens in the treatment of relapsed and refractory multiple myeloma: a multicenter real-world study from China","volume":"35","author":"Kuang","year":"2022","journal-title":"J Clin Hematol (China)"},{"key":"B57","doi-asserted-by":"publisher","first-page":"247","DOI":"10.1080\/14740338.2023.2248888","article-title":"Safety of selinexor as the only exportin 1 (XPO1) inhibitor so far: a post-marketing study based on the world health organization pharmacovigilance database (vigibase)","volume":"23","author":"Chen","year":"2024","journal-title":"Expert Opin Drug Saf"},{"key":"B58","doi-asserted-by":"publisher","first-page":"108","DOI":"10.1186\/s12916-022-02305-4","article-title":"Selinexor plus low-dose dexamethasone in Chinese patients with relapsed\/refractory multiple myeloma previously treated with an immunomodulatory agent and a proteasome inhibitor (MARCH): a phase II, single-arm study","volume":"20","author":"Qiu","year":"2022","journal-title":"BMC Med"},{"key":"B59","doi-asserted-by":"publisher","first-page":"2430","DOI":"10.1038\/s41375-020-0756-6","article-title":"Integrated safety profile of selinexor in multiple myeloma: experience from 437 patients enrolled in clinical trials","volume":"34","author":"Gavriatopoulou","year":"2020","journal-title":"Leukemia"},{"key":"B60","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1016\/j.clml.2019.12.026","article-title":"Consensus Recommendations for the clinical management of patients with multiple myeloma treated with selinexor","volume":"20","author":"Mikhael","year":"2020","journal-title":"Clin Lymphoma Myeloma Leuk"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1927209\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T09:20:50Z","timestamp":1791364850000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2026.1927209\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,6]]},"references-count":60,"alternative-id":["10.3389\/fmed.2026.1927209"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2026.1927209","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,6]]},"article-number":"1927209"}}