{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T20:19:24Z","timestamp":1791404364560,"version":"4.3.3"},"reference-count":31,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T00:00:00Z","timestamp":1749427200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Karyopharm Therapeutics"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Background: The remarkable efficacy of B-cell maturation antigen (BCMA)-directed chimeric antigen receptor T-cell therapy (CAR-T) has had a significant impact on treatment strategies for relapsed\/refractory multiple myeloma (RRMM). However, response durability remains a concern, necessitating the optimization of CAR-T procedures. Therapies preceding CAR-T therapy are crucial for disease control and preserving T-cell fitness. Methods: This review summarizes the evidence supporting the potential of selinexor-based regimens as holding or bridging therapy with preclinical research, demonstrating selinexor\u2019s ability to foster an anti-inflammatory tumor microenvironment. Results: Selinexor enhances CD8+ T-lymphocyte and NK cell activation, re-polarizes macrophages, and inhibits immunosuppressive cells. Bone marrow samples from patients in clinical studies show that selinexor increases CD8 and granzyme B expression in T-cells. Selinexor also disrupts NK cell inhibition, enhances anti-tumor activity, and reduces pro-inflammatory cytokines. Selinexor may upregulate BCMA expression and increase myeloma cell immunogenicity. Real-world data suggests selinexor as bridging therapy does not compromise CAR-T outcomes and may even improve them. Conclusions: Overall, the evidence indicates selinexor\u2019s potential to optimize CAR-T outcomes, warranting further investigation as a holding or bridging therapy for CAR-T.<\/jats:p>","DOI":"10.3390\/jcm14124071","type":"journal-article","created":{"date-parts":[[2025,6,9]],"date-time":"2025-06-09T06:46:01Z","timestamp":1749451561000},"page":"4071","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Focusing on Selinexor for Holding and Bridging Prior to CAR-T in Relapsed\/Refractory Multiple Myeloma"],"prefix":"10.3390","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2473-6528","authenticated-orcid":false,"given":"Jack","family":"Khouri","sequence":"first","affiliation":[{"name":"Department of Hematology and Medical Oncology, Cleveland Clinic, Cleveland, OH 44195, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4268-2698","authenticated-orcid":false,"given":"Douglas","family":"Sborov","sequence":"additional","affiliation":[{"name":"University of Utah Huntsman Cancer Institute, Salt Lake City, UT 84112, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-9914-5628","authenticated-orcid":false,"given":"Adriana","family":"Rossi","sequence":"additional","affiliation":[{"name":"Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Martin","sequence":"additional","affiliation":[{"name":"Helen Diller Family Comprehensive Cancer Center, San Francisco Medical Center, University of California, San Francisco, CA 94143, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Trinayan","family":"Kashyap","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics, Newton, MA 02459, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomer","family":"Mark","sequence":"additional","affiliation":[{"name":"Karyopharm Therapeutics, Newton, MA 02459, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Muhamed","family":"Baljevic","sequence":"additional","affiliation":[{"name":"Vanderbilt University Medical Center, Nashville, TN 37232, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s00277-022-05058-5","article-title":"The Emerging Therapeutic Landscape of Relapsed\/Refractory Multiple Myeloma","volume":"102","author":"Tanenbaum","year":"2023","journal-title":"Ann. 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