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Pharmacol."],"abstract":"<jats:p>Over the past few decades, the landscape for multiple myeloma (MM) therapy has significantly advanced, largely due to the approval and introduction of new-generation proteasome inhibitors (PIs) and immunomodulatory drugs (IMiDs). Despite these advancements, MM remains incurable. In March 2021, the U.S. FDA approved the chimeric antigen receptor T-cell (CAR-T) therapy idecabtagene vicleucel (ide-cel) for relapsed\/refractory multiple myeloma (R\/R MM), heralding the advent of cellular therapies for R\/R MM. However, due to factors such as the downregulation or loss of tumor antigen expression, T-cell exhaustion, and the influence of the tumor immune microenvironment, most R\/R MM patients inevitably experience relapse following CAR-T cell therapy. Consequently, salvage therapy in the post-CAR-T setting has emerged as a critical area of research. This review discusses the potential factors leading to CAR-T therapy failure in R\/R MM patients and discusses subsequent salvage therapeutic strategies, offering recommendations for addressing treatment failure in this context.<\/jats:p>","DOI":"10.3389\/fphar.2025.1515555","type":"journal-article","created":{"date-parts":[[2025,3,17]],"date-time":"2025-03-17T08:19:31Z","timestamp":1742199571000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Strategies for salvage therapy post CAR-T therapy failure in refractory\/relapsed multiple myeloma patients"],"prefix":"10.3389","volume":"16","author":[{"given":"Chao","family":"Min","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiong","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yue","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanfu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qingming","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,3,17]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"109933","DOI":"10.1016\/j.radonc.2023.109933","article-title":"Radiation therapy as a bridging and salvage strategy in patients with relapsed or refractory multiple myeloma undergoing BCMA-targeted CAR T-cell therapy","volume":"189","author":"Ababneh","year":"2023","journal-title":"Radiother. 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