{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:32:14Z","timestamp":1790721134959,"version":"4.1.0"},"reference-count":10,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T00:00:00Z","timestamp":1781913600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Exp Hematol Oncol"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>T-cell-redirecting therapies, including bispecific T-cell engagers (BiTEs) and chimeric antigen receptor T-cell (CAR-T) therapies, have substantially improved outcomes in relapsed or refractory multiple myeloma (RRMM). However, infectious complications remain a major safety concern, particularly in real-world settings, where patients are more heterogeneous than those enrolled in clinical trials.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We conducted a systematic review and meta-analysis of real-world retrospective studies evaluating severe (grade 3\u20134) infections in adult patients with RRMM treated with approved BiTEs or CAR-T cell therapies. Pooled event rates were estimated using random-effects models. Heterogeneity was explored through subgroup analyses, meta-regression, and sensitivity analyses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Sixteen studies encompassing 2,097 patients were included. Overall, 24.2% of patients developed grade 3\u20134 infections (pooled event rate 0.24; 95% CI, 0.21\u20130.28). Among BiTEs-treated patients (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u20091,602), the pooled severe infection rate was 0.26 (95% CI, 0.23\u20130.30), with higher rates observed for BCMA-directed BiTEs (0.27) compared with GPRC5D-directed BiTEs (0.25). CAR-T cell therapies (\n                      <jats:italic>n<\/jats:italic>\n                      \u2009=\u2009495) were associated with a lower pooled infection rate (0.19; 95% CI, 0.12\u20130.27).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>In real-world practice, severe infections affect approximately one in four patients receiving T-cell-redirecting therapies for RRMM. Observed differences in infection rates across platforms and targets should be interpreted with caution, as they derive from indirect comparisons in non-randomized, heterogeneous cohorts. Nevertheless, these data support incorporating patient frailty and prior infection history into therapeutic decision-making. CAR-T therapy, or GPRC5D-directed BiTEs when CAR-T is not feasible, may represent reasonable options in patients at higher infectious risk, within an individualized and context-dependent treatment strategy.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s40164-026-00798-w","type":"journal-article","created":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:27:34Z","timestamp":1781936854000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Real-world evidence on infection risk in multiple myeloma treated with BiTEs and CAR-T cells: a meta-analysis"],"prefix":"10.1186","volume":"15","author":[{"given":"Federico","family":"Spataro","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Desantis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Dicuonzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefano","family":"Molica","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Einsele","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelo","family":"Vacca","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberto","family":"Ria","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio Giovanni","family":"Solimando","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,6,20]]},"reference":[{"key":"798_CR1","doi-asserted-by":"publisher","first-page":"e143","DOI":"10.1016\/S2352-3026(21)00283-0","volume":"9","author":"NS Raje","year":"2022","unstructured":"Raje NS, Anaissie E, Kumar SK, et al. Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group. Lancet Haematol. 2022;9:e143\u201361.","journal-title":"Lancet Haematol"},{"key":"798_CR2","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2025.288174","author":"H Vandenboom","year":"2025","unstructured":"Vandenboom H, Akhtar O, Szabo A, et al. Safety and efficacy of BCMA CAR-T vs. bispecific antibodies in patients with relapsed multiple myeloma: a systematic review and meta-analysis. Haematologica. 2025. https:\/\/doi.org\/10.3324\/haematol.2025.288174.","journal-title":"Haematologica"},{"key":"798_CR3","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.n71","author":"MJ Page","year":"2021","unstructured":"Page MJ, McKenzie JE, Bossuyt PM, Boutron I, Hoffmann TC, Mulrow CD, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ. 2021. https:\/\/doi.org\/10.1136\/bmj.n71.","journal-title":"BMJ"},{"key":"798_CR4","doi-asserted-by":"publisher","first-page":"5898","DOI":"10.1182\/bloodadvances.2023010539","volume":"7","author":"G Reynolds","year":"2023","unstructured":"Reynolds G, Cliff ERS, Mohyuddin GR, et al. Infections following bispecific antibodies in myeloma: a systematic review and meta-analysis. Blood Adv. 2023;7:5898\u2013903.","journal-title":"Blood Adv"},{"key":"798_CR5","doi-asserted-by":"publisher","first-page":"1348955","DOI":"10.3389\/fimmu.2024.1348955","volume":"15","author":"X Wang","year":"2024","unstructured":"Wang X, Zhao A, Zhu J, et al. Efficacy and safety of bispecific antibodies therapy for relapsed or refractory multiple myeloma: a systematic review and meta-analysis of prospective clinical trials. Front Immunol. 2024;15:1348955.","journal-title":"Front Immunol"},{"key":"798_CR6","doi-asserted-by":"publisher","first-page":"1565407","DOI":"10.3389\/fimmu.2025.1565407","volume":"16","author":"W Li","year":"2025","unstructured":"Li W, Zhao D, Jiao Y, et al. Effectiveness and safety of teclistamab for relapsed or refractory multiple myeloma: a systematic review and meta-analysis. Front Immunol. 2025;16:1565407.","journal-title":"Front Immunol"},{"key":"798_CR7","doi-asserted-by":"publisher","first-page":"2727","DOI":"10.3390\/cancers17172727","volume":"17","author":"S Bakogeorgou","year":"2025","unstructured":"Bakogeorgou S, Filippatos C, Malandrakis P, et al. Safety and Efficacy of Bispecific Antibody Treatment in Relapsed\/Refractory Multiple Myeloma: A Systematic Review and Meta-Analysis of Proportions from Clinical Trials. Cancers (Basel). 2025;17:2727.","journal-title":"Cancers (Basel)"},{"key":"798_CR8","doi-asserted-by":"publisher","first-page":"4791","DOI":"10.1007\/s00277-025-06524-6","volume":"104","author":"P Techaapornkun","year":"2025","unstructured":"Techaapornkun P, Rojpalakorn W, Mejun N, et al. Comparative efficacy and safety of BCMA-targeted CAR T cells and BiTEs in relapsed\/refractory multiple myeloma: a meta-analysis of interventional and real-world studies. Ann Hematol. 2025;104:4791\u2013809.","journal-title":"Ann Hematol"},{"key":"798_CR9","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. International Myeloma Working Group immunotherapy committee consensus guidelines and recommendations for optimal use of T-cell-engaging bispecific antibodies in multiple myeloma. Lancet Oncol. 2024;25:e205\u201316.","journal-title":"Lancet Oncol"},{"key":"798_CR10","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-026-02880-y","author":"F Di Spataro","year":"2026","unstructured":"Spataro F, Armentaro G, Di Gioia G. Impact of frailty on infection risk in non-transplant eligible multiple myeloma patients: a systematic review and meta-analysis. Leukemia. 2026;40:1072\u20135. https:\/\/doi.org\/10.1038\/s41375-026-02880-y.","journal-title":"Leukemia"}],"container-title":["Experimental Hematology &amp; Oncology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00798-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/article\/10.1186\/s40164-026-00798-w","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/link.springer.com\/content\/pdf\/10.1186\/s40164-026-00798-w.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,6,20]],"date-time":"2026-06-20T06:27:34Z","timestamp":1781936854000},"score":1,"resource":{"primary":{"URL":"https:\/\/link.springer.com\/10.1186\/s40164-026-00798-w"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,6,20]]},"references-count":10,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,12]]}},"alternative-id":["798"],"URL":"https:\/\/doi.org\/10.1186\/s40164-026-00798-w","relation":{},"ISSN":["2162-3619"],"issn-type":[{"value":"2162-3619","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,6,20]]},"assertion":[{"value":"15 May 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"9 June 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"20 June 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":"Not applicable.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}},{"value":"Not applicable.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Consent for publication"}},{"value":"SM received consulting honoraria from Janssen, AbbVie, Astra-Zeneca and Lilly. H.E. received honoraria for Bristol-Myers-Squibb, Celgene, Janssen, Amgen, Takeda, Sanofi, GSK, Novartis, Roche, Research Funding (BMS\/Celgene, Janssen, Sanofi; GSK, Amgen) Consultancy (Amgen, BMS, Celgene, Janssen, GSK, Novartis, Roche, Sanofi, Takeda); A.V. received speaker honorariums from Pfizer, Sanofi, Bristol Myers Squibb, Takeda, Janssen Cilag, AstraZeneca, Menarini, and Amgen; R.R. has served as a speaker or consultant for Amgen, BMS-Celgene, CSL Behring, Janssen Cilag, Octapharma, Pfizer, Sanofi, Takeda; A.G.S. has received speaker honorariums from Sanofi, Amgen, and AstraZeneca. He has also participated on advisory boards for Pfizer and Menarini. He received travel support for educational purposes from Janssen Cilag. These potential conflicts of interest do not imply bias or influence on the authors\u2019 opinions or actions. The authors are aware of the importance of transparency in the scientific field and are committed to defending their integrity and the trust in them within the scientific community.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"56"}}