{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T21:51:35Z","timestamp":1781646695821,"version":"3.54.5"},"reference-count":13,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:00:00Z","timestamp":1774483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/100007195","name":"Universit\u00e0 degli Studi di Napoli Federico II","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100007195","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Ann Hematol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Bispecific antibodies targeting B-cell maturation antigen, BCMA (teclistamab) or G protein\u2013coupled receptor, class C, group 5 member D, GPRC5D (talquetamab) are effective treatments for relapsed or refractory multiple myeloma. Their main early toxicity is cytokine release syndrome (CRS), usually transient and limited to initial cycles. We report five patients with relapsed or refractory multiple myeloma who received bispecific antibodies (n\u2009=\u20091 teclistamab; n\u2009=\u20094 talquetamab) who developed a pattern of recurrent, cyclic CRS beyond the initial step-up phase. All patients achieved at least a partial hematologic response, with complete or stringent complete remission in most cases. Recurrent febrile episodes occurred at regular intervals after drug administration, despite repeatedly negative infectious workups. CRS episodes were generally grade 1\u20132 and resolved with tocilizumab, with or without corticosteroids. In one patient treated with teclistamab, recurrent CRS contributed to treatment discontinuation due to renal complications. Attenuation of CRS severity over time was observed in some patients, allowing treatment continuation with tailored premedication strategies. This case series describes an unusual pattern of recurrent CRS occurring during bispecific antibody therapy for multiple myeloma. Recognition of this phenomenon is essential to avoid misdiagnosis as infection and unnecessary antimicrobial use. Systematic reporting of such real-world adverse events may help refine supportive care strategies.<\/jats:p>","DOI":"10.1007\/s00277-026-06966-6","type":"journal-article","created":{"date-parts":[[2026,3,26]],"date-time":"2026-03-26T00:43:09Z","timestamp":1774485789000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Recurrent cytokine release syndrome in patients receiving bispecific antibody therapy for multiple myeloma: a case series"],"prefix":"10.1007","volume":"105","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5641-231X","authenticated-orcid":false,"given":"Roberta","family":"Della Pepa","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7148-7122","authenticated-orcid":false,"given":"Aldo","family":"Leone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4365-9406","authenticated-orcid":false,"given":"Francesco","family":"Grimaldi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Simona","family":"Avilia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1922-6048","authenticated-orcid":false,"given":"Mara","family":"Memoli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2348-5437","authenticated-orcid":false,"given":"Bernardo","family":"Rossini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0948-9343","authenticated-orcid":false,"given":"Carmine","family":"Liberatore","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2563-4125","authenticated-orcid":false,"given":"Fabrizio","family":"Pane","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,3,26]]},"reference":[{"issue":"4","key":"6966_CR1","doi-asserted-by":"publisher","first-page":"e269","DOI":"10.1016\/S2352-3026(24)00385-5","volume":"12","author":"A Chari","year":"2025","unstructured":"Chari A, Touzeau C, Schinke C et al (2025) Safety and activity of talquetamab in patients with relapsed or refractory multiple myeloma (MonumenTAL-1): a multicentre, open-label, phase 1\u20132 study. Lancet Haematol 12(4):e269\u2013e281. https:\/\/doi.org\/10.1016\/S2352-3026(24)00385-5","journal-title":"Lancet Haematol"},{"issue":"5","key":"6966_CR2","doi-asserted-by":"publisher","first-page":"e205","DOI":"10.1016\/S1470-2045(24)00043-3","volume":"25","author":"P Rodriguez-Otero","year":"2024","unstructured":"Rodriguez-Otero P, Usmani S, Cohen AD et al (2024) International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. Lancet Oncol 25(5):e205\u2013e216. https:\/\/doi.org\/10.1016\/S1470-2045(24)00043-3","journal-title":"Lancet Oncol"},{"key":"6966_CR3","doi-asserted-by":"publisher","unstructured":"Lee H, Neri P, Bahlis N (2024) BCMA- or GPRC5D-targeting bispecific antibodies in multiple myeloma: Efficacy, safety and resi stance mechanisms. Blood 143. https:\/\/doi.org\/10.1182\/blood.2023022499","DOI":"10.1182\/blood.2023022499"},{"issue":"10301","key":"6966_CR4","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1016\/S0140-6736(21)01338-6","volume":"398","author":"SZ Usmani","year":"2021","unstructured":"Usmani SZ, Garfall AL, van de Donk NWCJ et al (2021) Teclistamab, a B-cell maturation antigen \u00d7 CD3 bispecific antibody, in patients with relapsed or refractory multiple myeloma (MajesTEC-1): a multicentre, open-label, single-arm, phase 1 study. Lancet 398(10301):665\u2013674. https:\/\/doi.org\/10.1016\/S0140-6736(21)01338-6","journal-title":"Lancet"},{"issue":"13","key":"6966_CR5","doi-asserted-by":"publisher","first-page":"2035","DOI":"10.1002\/cncr.34756","volume":"129","author":"TG Martin","year":"2023","unstructured":"Martin TG, Mateos MV, Nooka A et al (2023) Detailed overview of incidence and management of cytokine release syndrome observed with teclistamab in the MajesTEC-1 study of patients with relapsed\/refractory multiple myeloma. Cancer 129(13):2035\u20132046. https:\/\/doi.org\/10.1002\/cncr.34756","journal-title":"Cancer"},{"issue":"6","key":"6966_CR6","doi-asserted-by":"publisher","first-page":"2123","DOI":"10.1172\/JCI85309","volume":"126","author":"CJ Turtle","year":"2016","unstructured":"Turtle CJ, Hanafi LA, Berger C et al (2016) CD19 CAR-T cells of defined CD4+:CD8\u2009+\u2009composition in adult B cell ALL patients. 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Cancer Cell 41(4):711\u2013725e6. https:\/\/doi.org\/10.1016\/j.ccell.2023.02.008","journal-title":"Cancer Cell"}],"container-title":["Annals of Hematology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06966-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1007\/s00277-026-06966-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1007\/s00277-026-06966-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T20:52:42Z","timestamp":1781643162000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1007\/s00277-026-06966-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,26]]},"references-count":13,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2026,4]]}},"alternative-id":["6966"],"URL":"https:\/\/doi.org\/10.1007\/s00277-026-06966-6","relation":{},"ISSN":["1432-0584"],"issn-type":[{"value":"1432-0584","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,26]]},"assertion":[{"value":"3 October 2025","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 March 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 March 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Declarations"}},{"value":"This case series is written in accordance with the Declaration of Helsinki\u2019s principles. Protocol was approved by local ethic committee (Ethics Committee \u201cCampania 3\u201d, Naples, Italy; DS prot. no. 1654\/2024). Written informed consent was obtained from all individual patients included in the case series.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval"}},{"value":"The authors declare no competing interests.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"206"}}