{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,5]],"date-time":"2026-11-05T19:35:14Z","timestamp":1793907314056,"version":"4.8.0"},"reference-count":38,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T00:00:00Z","timestamp":1768953600000},"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. Immunol."],"abstract":"<jats:p>Multiple Myeloma (MM), a highly treatable but thus far incurable hematologic malignancy, has required continuous monitoring and treatment throughout a patient\u2019s lifetime. Newer classes of therapies, such as chimeric antigen receptor (CAR) T-cell therapy which constitutes of a one-time infusion, have challenged the continuous treatment paradigm. Compared to previously known standard therapies, CAR T-cell therapy along with bispecific T-cell engager (BiTE) therapy have been observed to induce deeper responses that tend to be durable in responders. However, the degree of immunosuppression and infection noted especially with BiTE therapies, currently approved for ongoing administration until progression of disease, has given rise to the idea of incorporating treatment-free intervals. This review describes T-cell exhaustion as a driver for immunosuppression and infection in patients with MM receiving BiTE therapy and discusses potential ways to overcome it to improve management of patients.<\/jats:p>","DOI":"10.3389\/fimmu.2026.1705345","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:35:55Z","timestamp":1768973755000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":6,"title":["T-cell exhaustion due to BiTE therapy in multiple myeloma: mitigating infectious risks through treatment-free intervals"],"prefix":"10.3389","volume":"17","author":[{"given":"Erin A.","family":"Dean","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1182\/blood-2017-06-740944","article-title":"CD38 antibodies in multiple myeloma: back to the future","volume":"131","author":"van de Donk","year":"2018","journal-title":"Blood"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687749","article-title":"Daratumumab depletes CD38+ immune regulatory cells, promotes T-cell expansion, and skews T-cell repertoire in multiple myeloma","volume":"128","author":"Krejcik","year":"2016","journal-title":"Blood"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-2224","article-title":"Soluble B-cell maturation antigen mediates tumor-induced immune deficiency in multiple myeloma","volume":"22","author":"Sanchez","year":"2016","journal-title":"Clin Cancer Res"},{"key":"B4","doi-asserted-by":"publisher","first-page":"7333","DOI":"10.1038\/ncomms8333","article-title":"\u03b3-Secretase directly sheds the survival receptor BCMA from plasma cells","volume":"6","author":"Laurent","year":"2015","journal-title":"Nat Commun"},{"key":"B5","doi-asserted-by":"publisher","first-page":"24","DOI":"10.1038\/s41408-023-00966-9","article-title":"GPRC5D as a novel target for the treatment of multiple myeloma: a narrative review","volume":"14","author":"Rodriguez-Otero","year":"2024","journal-title":"Blood Cancer J"},{"key":"B6","unstructured":"Multiple myeloma. 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