{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,28]],"date-time":"2026-04-28T21:03:18Z","timestamp":1777410198642,"version":"3.51.4"},"reference-count":50,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T00:00:00Z","timestamp":1691107200000},"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. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Treatment of relapsed or refractory acute myeloid leukemia (R\/R AML) and myeloid sarcoma (MS) has presented challenges for decades. Studies on selinexor in combination with various standard or intensive chemotherapy regimens for the treatment of R\/R AML have demonstrated promising results. This study aimed to evaluate the efficacy and safety of chemotherapy-free or low-dose chemotherapy regimens with selinexor for R\/R AML and MS patients.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Ten patients with R\/R AML or MS who received chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor at Tongji Hospital from October 2021 to August 2022 were included in this study. The primary endpoint was overall response rate (ORR) and secondary endpoints included complete remission (CR), CR with incomplete hematological recovery (CRi), partial remission (PR), transplantation rate, and safety.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> All patients were evaluable for response, achieving CR in four (40.0%) patients and CRi in two (20.0%) patients for a total CR\/CRi of 60.0%. The ORR was 80.0% when patients with PR were included. Five (50.0%) patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT) after treatment with selinexor-containing regimens. At the end of the follow-up, seven (70.0%) patients were alive, and three patients died of transplant-related complications or disease progression. The most frequently reported nonhematologic adverse events (AEs) in patients were grade 1 or 2 asymptomatic hyponatremia.<\/jats:p><jats:p><jats:bold>Conclusion:<\/jats:bold> The chemotherapy-free or low-dose chemotherapy regimens in combination with selinexor for R\/R AML are feasible and tolerable and provide an opportunity for patients to receive transplantation.<\/jats:p>","DOI":"10.3389\/fphar.2023.1217701","type":"journal-article","created":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:14:25Z","timestamp":1691151265000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Real-world experience with selinexor-containing chemotherapy-free or low-dose chemotherapy regimens for patients with relapsed\/refractory acute myeloid leukemia and myeloid sarcoma"],"prefix":"10.3389","volume":"14","author":[{"given":"Xiwen","family":"Tong","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Jin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bin","family":"Xu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuai","family":"Su","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mengyuan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yizhou","family":"Peng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Mao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei","family":"Huang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Donghua","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2023,8,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"e404","DOI":"10.3324\/haematol.2019.236810","article-title":"Selinexor combined with cladribine, cytarabine, and filgrastim in relapsed or refractory acute myeloid leukemia","volume":"105","author":"Abboud","year":"2020","journal-title":"Haematologica"},{"key":"B2","doi-asserted-by":"publisher","first-page":"4142","DOI":"10.1200\/jco.2015.65.3949","article-title":"First-in-Class, first-in-human phase I study of selinexor, a selective inhibitor of nuclear export, in patients with advanced solid tumors","volume":"34","author":"Abdul Razak","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"4094","DOI":"10.1200\/JCO.2016.67.5066","article-title":"Phase I study of selinexor, a selective inhibitor of nuclear export, in combination with fludarabine and cytarabine, in pediatric relapsed or refractory acute leukemia","volume":"34","author":"Alexander","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"3785","DOI":"10.1182\/blood-2011-04-347229","article-title":"How I treat extramedullary acute myeloid leukemia","volume":"118","author":"Bakst","year":"2011","journal-title":"Blood"},{"key":"B5","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1080\/10428194.2019.1665664","article-title":"Selinexor in combination with decitabine in patients with acute myeloid leukemia: Results from a phase 1 study","volume":"61","author":"Bhatnagar","year":"2020","journal-title":"Leuk. Lymphoma"},{"key":"B6","doi-asserted-by":"publisher","first-page":"1657","DOI":"10.1038\/leu.2014.44","article-title":"BCL-2 family proteins as 5-Azacytidine-sensitizing targets and determinants of response in myeloid malignancies","volume":"28","author":"Bogenberger","year":"2014","journal-title":"Leukemia"},{"key":"B7","doi-asserted-by":"publisher","first-page":"288","DOI":"10.1038\/s41392-020-00361-x","article-title":"Targeting multiple signaling pathways: The new approach to acute myeloid leukemia therapy","volume":"5","author":"Carter","year":"2020","journal-title":"Signal Transduct. Target Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1701","DOI":"10.1038\/s41375-022-01625-x","article-title":"The WHO classification of haematolymphoid tumours","volume":"36","author":"Cree","year":"2022","journal-title":"Leukemia"},{"key":"B9","doi-asserted-by":"publisher","first-page":"7","DOI":"10.1186\/s40164-015-0002-5","article-title":"Selective inhibitors of nuclear export (SINE) in hematological malignancies","volume":"4","author":"Das","year":"2015","journal-title":"Exp. Hematol. Oncol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"1023","DOI":"10.1182\/blood.2019001982","article-title":"How I treat relapsed or refractory AML","volume":"136","author":"DeWolf","year":"2020","journal-title":"Blood"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e724","DOI":"10.1016\/s2352-3026(20)30210-6","article-title":"10-day decitabine with venetoclax for newly diagnosed intensive chemotherapy ineligible, and relapsed or refractory acute myeloid leukaemia: A single-centre, phase 2 trial","volume":"7","author":"DiNardo","year":"2020","journal-title":"Lancet Haematol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"1345","DOI":"10.1182\/blood.2022016867","article-title":"Diagnosis and management of AML in adults: 2022 recommendations from an international expert panel on behalf of the ELN","volume":"140","author":"D\u00f6hner","year":"2022","journal-title":"Blood"},{"key":"B13","doi-asserted-by":"publisher","first-page":"190","DOI":"10.1038\/leu.2015.194","article-title":"Activity of a selective inhibitor of nuclear export, selinexor (KPT-330), against AML-initiating cells engrafted into immunosuppressed NSG mice","volume":"30","author":"Etchin","year":"2016","journal-title":"Leukemia"},{"key":"B14","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1111\/bjh.12231","article-title":"KPT-330 inhibitor of CRM1 (XPO1)-mediated nuclear export has selective anti-leukaemic activity in preclinical models of T-cell acute lymphoblastic leukaemia and acute myeloid leukaemia","volume":"161","author":"Etchin","year":"2013","journal-title":"Br. J. Haematol."},{"key":"B15","first-page":"998","article-title":"Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia","volume":"89","author":"Ferrara","year":"2004","journal-title":"Haematologica"},{"key":"B16","doi-asserted-by":"publisher","first-page":"e169","DOI":"10.1111\/bjh.16804","article-title":"A Phase II study of selinexor plus cytarabine and idarubicin in patients with relapsed\/refractory acute myeloid leukaemia","volume":"190","author":"Fiedler","year":"2020","journal-title":"Br. J. Haematol."},{"key":"B17","doi-asserted-by":"publisher","first-page":"586","DOI":"10.1182\/bloodadvances.2019000359","article-title":"Venetoclax response is enhanced by selective inhibitor of nuclear export compounds in hematologic malignancies","volume":"4","author":"Fischer","year":"2020","journal-title":"Blood Adv."},{"key":"B18","doi-asserted-by":"publisher","first-page":"3165","DOI":"10.1182\/blood-2016-11-750158","article-title":"A phase 1 clinical trial of single-agent selinexor in acute myeloid leukemia","volume":"129","author":"Garzon","year":"2017","journal-title":"Blood"},{"key":"B19","doi-asserted-by":"publisher","first-page":"155","DOI":"10.1186\/s13045-020-00992-1","article-title":"Therapeutic targeting of FLT3 and associated drug resistance in acute myeloid leukemia","volume":"13","author":"Gebru","year":"2020","journal-title":"J. Hematol. Oncol."},{"key":"B20","doi-asserted-by":"publisher","first-page":"2753","DOI":"10.1182\/blood.2021013626","article-title":"2021 update on MRD in acute myeloid leukemia: A consensus document from the European LeukemiaNet MRD working party","volume":"138","author":"Heuser","year":"2021","journal-title":"Blood"},{"key":"B21","doi-asserted-by":"publisher","first-page":"2364","DOI":"10.1038\/leu.2016.136","article-title":"Next-generation XPO1 inhibitor shows improved efficacy and in vivo tolerability in hematological malignancies","volume":"30","author":"Hing","year":"2016","journal-title":"Leukemia"},{"key":"B22","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1016\/j.pharmthera.2015.06.001","article-title":"Expression, function, and targeting of the nuclear exporter chromosome region maintenance 1 (CRM1) protein","volume":"153","author":"Ishizawa","year":"2015","journal-title":"Pharmacol. Ther."},{"key":"B23","doi-asserted-by":"publisher","first-page":"635","DOI":"10.1097\/cco.0000000000000780","article-title":"The changing landscape for patients with relapsed\/refractory acute myeloid leukaemia","volume":"33","author":"Isidori","year":"2021","journal-title":"Curr. Opin. Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"395","DOI":"10.1002\/ajh.23655","article-title":"Allogeneic stem cell transplantation as initial salvage for patients with acute myeloid leukemia refractory to high-dose cytarabine-based induction chemotherapy","volume":"89","author":"Jabbour","year":"2014","journal-title":"Am. J. Hematol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"551","DOI":"10.1016\/s1470-2045(20)30060-7","article-title":"Venetoclax in combination with cytarabine with or without idarubicin in children with relapsed or refractory acute myeloid leukaemia: A phase 1, dose-escalation study","volume":"21","author":"Karol","year":"2020","journal-title":"Lancet Oncol."},{"key":"B26","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1111\/bjh.17746","article-title":"Updates on targeted therapies for acute myeloid leukaemia","volume":"196","author":"Kayser","year":"2022","journal-title":"Br. J. Haematol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1586","DOI":"10.1038\/leu.2014.55","article-title":"Comprehensive analysis of genetic alterations and their prognostic impacts in adult acute myeloid leukemia patients","volume":"28","author":"Kihara","year":"2014","journal-title":"Leukemia"},{"key":"B28","doi-asserted-by":"publisher","first-page":"4166","DOI":"10.1182\/blood-2012-08-447581","article-title":"Prognostic impact and targeting of CRM1 in acute myeloid leukemia","volume":"121","author":"Kojima","year":"2013","journal-title":"Blood"},{"key":"B29","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":"B30","doi-asserted-by":"publisher","first-page":"6099","DOI":"10.1111\/jcmm.13886","article-title":"Inhibition of XPO1 enhances cell death induced by ABT-199 in acute myeloid leukaemia via Mcl-1","volume":"22","author":"Luedtke","year":"2018","journal-title":"J. Cell Mol. Med."},{"key":"B31","doi-asserted-by":"publisher","first-page":"409","DOI":"10.17305\/bjbms.2020.5485","article-title":"Recent advances of targeted therapy in relapsed\/refractory acute myeloid leukemia","volume":"21","author":"Ma","year":"2021","journal-title":"Bosn. J. Basic Med. Sci."},{"key":"B32","doi-asserted-by":"publisher","first-page":"1497","DOI":"10.1007\/s00277-021-04542-8","article-title":"A phase I trial of selinexor plus FLAG-Ida for the treatment of refractory\/relapsed adult acute myeloid leukemia patients","volume":"100","author":"Martinez Sanchez","year":"2021","journal-title":"Ann. Hematol."},{"key":"B33","doi-asserted-by":"publisher","first-page":"88","DOI":"10.1097\/moh.0000000000000490","article-title":"Progress in the problem of relapsed or refractory acute myeloid leukemia","volume":"26","author":"Mims","year":"2019","journal-title":"Curr. Opin. Hematol."},{"key":"B34","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1038\/leu.2014.72","article-title":"Acute myeloid leukemia cells harboring MLL fusion genes or with the acute promyelocytic leukemia phenotype are sensitive to the Bcl-2-selective inhibitor ABT-199","volume":"28","author":"Niu","year":"2014","journal-title":"Leukemia"},{"key":"B35","doi-asserted-by":"publisher","first-page":"559","DOI":"10.1016\/j.bbmt.2014.10.025","article-title":"Fate of patients with newly diagnosed acute myeloid leukemia who fail primary induction therapy","volume":"21","author":"Othus","year":"2015","journal-title":"Biol. Blood Marrow Transpl."},{"key":"B36","doi-asserted-by":"publisher","first-page":"536","DOI":"10.1158\/2159-8290.Cd-19-0710","article-title":"Monocytic subclones confer resistance to venetoclax-based therapy in patients with acute myeloid leukemia","volume":"10","author":"Pei","year":"2020","journal-title":"Cancer Discov."},{"key":"B37","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41408-022-00677-7","article-title":"Clinical outcomes in patients with relapsed\/refractory FLT3-mutated acute myeloid leukemia treated with gilteritinib who received prior midostaurin or sorafenib","volume":"12","author":"Perl","year":"2022","journal-title":"Blood Cancer J."},{"key":"B38","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1002\/ajh.26039","article-title":"Venetoclax with azacitidine or decitabine in patients with newly diagnosed acute myeloid leukemia: Long term follow-up from a phase 1b study","volume":"96","author":"Pollyea","year":"2021","journal-title":"Am. J. Hematol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"1765","DOI":"10.1182\/blood-2012-04-423160","article-title":"Preclinical activity of a novel CRM1 inhibitor in acute myeloid leukemia","volume":"120","author":"Ranganathan","year":"2012","journal-title":"Blood"},{"key":"B40","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1111\/bjh.15077","article-title":"Treatment of relapsed\/refractory acute myeloid leukaemia in adults","volume":"181","author":"Rashidi","year":"2018","journal-title":"Br. J. Haematol."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1016\/s1470-2045(15)00362-9","article-title":"Addition of sorafenib versus placebo to standard therapy in patients aged 60 years or younger with newly diagnosed acute myeloid leukaemia (SORAML): A multicentre, phase 2, randomised controlled trial","volume":"16","author":"R\u00f6llig","year":"2015","journal-title":"Lancet Oncol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1016\/j.semcancer.2014.04.005","article-title":"Clinical translation of nuclear export inhibitors in cancer","volume":"27","author":"Senapedis","year":"2014","journal-title":"Semin. Cancer Biol."},{"key":"B43","doi-asserted-by":"publisher","first-page":"12248","DOI":"10.1038\/s41598-018-30686-1","article-title":"Anti-tumor efficacy of Selinexor (KPT-330) in gastric cancer is dependent on nuclear accumulation of p53 tumor suppressor","volume":"8","author":"Subhash","year":"2018","journal-title":"Sci. Rep."},{"key":"B44","doi-asserted-by":"publisher","first-page":"721","DOI":"10.6004\/jnccn.2019.0028","article-title":"Acute myeloid leukemia, version 3.2019, NCCN clinical practice guidelines in Oncology","volume":"17","author":"Tallman","year":"2019","journal-title":"J. Natl. Compr. Canc Netw."},{"key":"B45","doi-asserted-by":"publisher","first-page":"e0242497","DOI":"10.1371\/journal.pone.0242497","article-title":"Renin angiotensin system genes are biomarkers for personalized treatment of acute myeloid leukemia with Doxorubicin as well as etoposide","volume":"15","author":"Turk","year":"2020","journal-title":"PLoS One"},{"key":"B46","doi-asserted-by":"publisher","first-page":"1552","DOI":"10.1007\/s11427-019-1610-2","article-title":"Impact of prophylactic\/preemptive donor lymphocyte infusion and intensified conditioning for relapsed\/refractory leukemia: A real-world study","volume":"63","author":"Wang","year":"2020","journal-title":"Sci. China Life Sci."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2137","DOI":"10.1182\/blood.2020004856","article-title":"Venetoclax plus LDAC for newly diagnosed AML ineligible for intensive chemotherapy: A phase 3 randomized placebo-controlled trial","volume":"135","author":"Wei","year":"2020","journal-title":"Blood"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1277","DOI":"10.1200\/jco.18.01600","article-title":"Venetoclax combined with low-dose cytarabine for previously untreated patients with acute myeloid leukemia: Results from a phase ib\/II study","volume":"37","author":"Wei","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"2911","DOI":"10.1182\/bloodadvances.2019000243","article-title":"Real-world experience of venetoclax with azacitidine for untreated patients with acute myeloid leukemia","volume":"3","author":"Winters","year":"2019","journal-title":"Blood Adv."},{"key":"B50","doi-asserted-by":"publisher","first-page":"51","DOI":"10.1038\/s41392-021-00870-3","article-title":"Activation of RAS\/MAPK pathway confers MCL-1 mediated acquired resistance to BCL-2 inhibitor venetoclax in acute myeloid leukemia","volume":"7","author":"Zhang","year":"2022","journal-title":"Signal Transduct. Target Ther."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1217701\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,4]],"date-time":"2023-08-04T12:14:29Z","timestamp":1691151269000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1217701\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,8,4]]},"references-count":50,"alternative-id":["10.3389\/fphar.2023.1217701"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1217701","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,8,4]]},"article-number":"1217701"}}