{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T16:35:52Z","timestamp":1793378152604,"version":"4.5.0"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T00:00:00Z","timestamp":1767657600000},"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. Oncol."],"abstract":"<jats:p>Daratumumab, a CD38-targeting monoclonal antibody, is a key component of therapy for both newly diagnosed and relapsed or refractory multiple myeloma. By depleting CD38-expressing immune effector cells and reducing immunoglobulin levels, daratumumab may increase susceptibility to infections. To quantify this risk, we performed a systematic review and meta-analysis of randomized phase II and III trials comparing daratumumab-containing regimens with standard therapies in adults with multiple myeloma. Databases including PubMed, Embase, Web of Science, the Cochrane Library, and ClinicalTrials.gov were searched through 14 October 2025, following PRISMA 2020 guidelines. Nine trials encompassing 5,281 patients were included. Daratumumab-based regimens were associated with an increased risk of any infection (risk ratio [RR] 1.23; 95% confidence interval [CI] 1.14\u20131.33), grade \u22653 infection (RR 1.29; 95% CI 1.17\u20131.42), and pneumonia (RR 1.60; 95% CI 1.24\u20132.07). Subgroup analyses showed consistent results across disease stages and transplant eligibility groups. Infection-related mortality was uncommon (\u22642%) and did not differ significantly between arms. These findings indicate that daratumumab-based therapy increases infection risk, particularly for severe infections and pneumonia, but the absolute mortality remains low. Proactive infection prevention and close clinical monitoring are warranted as the use of daratumumab continues to expand. This study was prospectively registered in PROSPERO (CRD420251165266).<\/jats:p>\n                  <jats:sec>\n                    <jats:title>Systematic Review Registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/www.crd.york.ac.uk\/PROSPERO\/<\/jats:ext-link>\n                      , CRD420251165266.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2025.1729177","type":"journal-article","created":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:18:15Z","timestamp":1767676695000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Infection risks associated with daratumumab-containing regimens in multiple myeloma: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"15","author":[{"given":"Zeng-Yi","family":"Huang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Lian","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Han","family":"Luo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,1,6]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25791","article-title":"Multiple myeloma: 2020 update on diagnosis, risk-stratification and management","volume":"95","author":"Rajkumar","year":"2020","journal-title":"Am J Hematol"},{"key":"B2","doi-asserted-by":"crossref","DOI":"10.1634\/theoncologist.12-6-664","article-title":"New drugs for myeloma","volume":"12","author":"Richardson","year":"2007","journal-title":"Oncologist."},{"key":"B3","doi-asserted-by":"crossref","first-page":"17046","DOI":"10.1038\/nrdp.2017.46","article-title":"Multiple myeloma","volume":"3","author":"Kumar","year":"2017","journal-title":"Nat Rev Dis Primers."},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mdx096","article-title":"Multiple myeloma: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"28","author":"Moreau","year":"2017","journal-title":"Ann Oncol"},{"key":"B5","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1053\/j.seminoncol.2022.01.008","article-title":"Daratumumab: A review of current indications and future directions","volume":"49","author":"Hill","year":"2022","journal-title":"Semin Oncol"},{"key":"B6","doi-asserted-by":"crossref","DOI":"10.1016\/j.clml.2023.07.001","article-title":"Expert consensus on the incorporation of anti-CD38 monoclonal antibody therapy into the management of newly diagnosed multiple myeloma","volume":"23","author":"Lonial","year":"2023","journal-title":"Clin Lymphoma Myeloma Leuk."},{"key":"B7","article-title":"Darzalex (Daratumumab): first anti-CD38 monoclonal antibody approved for patients with relapsed multiple myeloma","volume":"9","author":"Raedler","year":"2016","journal-title":"Am Health Drug Benefits"},{"key":"B8","doi-asserted-by":"crossref","DOI":"10.1080\/19420862.2015.1007813","article-title":"Antibody-mediated phagocytosis contributes to the anti-tumor activity of the therapeutic antibody daratumumab in lymphoma and multiple myeloma","volume":"7","author":"Overdijk","year":"2015","journal-title":"MAbs."},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1519300","article-title":"Monoclonal anti-CD38 therapy in human myeloma: retrospects and prospects","volume":"16","author":"Horenstein","year":"2025","journal-title":"Front Immunol"},{"key":"B10","doi-asserted-by":"crossref","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":"B11","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2017006866","article-title":"Effects of daratumumab on natural killer cells and impact on clinical outcomes in relapsed or refractory multiple myeloma","volume":"1","author":"Casneuf","year":"2017","journal-title":"Blood Adv"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02134","article-title":"CD38 antibodies in multiple myeloma: mechanisms of action and modes of resistance","volume":"9","author":"van de Donk","year":"2018","journal-title":"Front Immunol"},{"key":"B13","doi-asserted-by":"crossref","DOI":"10.1080\/14740338.2023.2296966","article-title":"Safety of daratumumab in the real-world: a pharmacovigilance study based on FAERS database","volume":"23","author":"Wu","year":"2024","journal-title":"Expert Opin Drug Safety."},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2014.107714","article-title":"Multiple myeloma and infections: a population-based study on 9253 multiple myeloma patients","volume":"100","author":"Blimark","year":"2015","journal-title":"Haematologica."},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1606038","article-title":"Daratumumab, bortezomib, and dexamethasone for multiple myeloma","volume":"375","author":"Palumbo","year":"2016","journal-title":"N Engl J Med"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1817249","article-title":"Daratumumab plus lenalidomide and dexamethasone for untreated myeloma","volume":"380","author":"Facon","year":"2019","journal-title":"N Engl J Med"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.797","article-title":"Daratumumab provides a survival benefit in relapsed and refractory Multiple Myeloma, independent of baseline clinical characteristics: A meta-analysis","volume":"9","author":"Cao","year":"2021","journal-title":"Pharmacol Res Perspect"},{"key":"B18","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1182\/blood-2016-03-705210","article-title":"Clinical efficacy of daratumumab monotherapy in patients with heavily pretreated relapsed or refractory multiple myeloma","volume":"128","author":"Usmani","year":"2016","journal-title":"Blood."},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(21)00283-0","article-title":"Consensus guidelines and recommendations for infection prevention in multiple myeloma: a report from the International Myeloma Working Group","volume":"9","author":"Raje","year":"2022","journal-title":"Lancet Haematol"},{"key":"B20","doi-asserted-by":"crossref","DOI":"10.1002\/9781119536604","volume-title":"Cochrane handbook for systematic reviews of interventions","author":"Higgins","year":"2019"},{"key":"B21","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1186\/s13643-017-0644-y","article-title":"Optimal database combinations for literature searches in systematic reviews: a prospective exploratory study","volume":"6","author":"Bramer","year":"2017","journal-title":"Syst Rev"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.38636.593461.68","article-title":"Effectiveness and efficiency of search methods in systematic reviews of complex evidence: audit of primary sources","volume":"331","author":"Greenhalgh","year":"2005","journal-title":"Bmj."},{"key":"B23","doi-asserted-by":"publisher","first-page":"579","DOI":"10.1186\/s12913-014-0579-0","article-title":"PICOS and SPIDER: a comparison study of specificity and sensitivity in three search tools for qualitative systematic reviews","volume":"14","author":"Methley","year":"2014","journal-title":"BMC Health Serv Res"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1016\/j.adengl.2019.05.021","article-title":"Using the common terminology criteria for adverse events (CTCAE\u2013version 5.0) to evaluate the severity of adverse events of anticancer therapies","volume":"112","author":"Freites-Martinez","year":"2021","journal-title":"Actas Dermo-Sifiliogr\u00e1ficas (English Edition)"},{"key":"B25","doi-asserted-by":"publisher","first-page":"15","DOI":"10.1186\/1471-2288-11-15","article-title":"Methodology in conducting a systematic review of systematic reviews of healthcare interventions","volume":"11","author":"Smith","year":"2011","journal-title":"BMC Med Res Methodol"},{"key":"B26","volume-title":"Review manager (RevMan) [Computer program]. Version 5.4","year":"2020"},{"key":"B27","doi-asserted-by":"publisher","first-page":"l4898","DOI":"10.1136\/bmj.l4898","article-title":"RoB 2: a revised tool for assessing risk of bias in randomised trials","volume":"366","author":"Sterne","year":"2019","journal-title":"BMJ"},{"key":"B28","doi-asserted-by":"publisher","first-page":"1","DOI":"10.18637\/jss.v036.i03","article-title":"Conducting meta-analyses in R with the metafor package","volume":"36","author":"Viechtbauer","year":"2010","journal-title":"J Stat Software"},{"key":"B29","doi-asserted-by":"crossref","DOI":"10.1136\/bmj.327.7414.557","article-title":"Measuring inconsistency in meta-analyses","volume":"327","author":"Higgins","year":"2003","journal-title":"Bmj."},{"key":"B30","doi-asserted-by":"crossref","DOI":"10.1002\/9780470743386","volume-title":"Introduction to meta-analysis","author":"Borenstein","year":"2009"},{"key":"B31","doi-asserted-by":"crossref","DOI":"10.1002\/9781119536604.ch10","article-title":"Analysing data and undertaking meta-analyses","volume-title":"Cochrane handbook for systematic reviews of interventions","author":"Deeks","year":"2019"},{"key":"B32","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1002\/9780470693926.ch15","article-title":"Statistical methods for examining heterogeneity and combining results from several studies in meta-analysis","volume-title":"Systematic reviews in health care: meta-analysis in context","author":"Deeks","year":"2001"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyn065","article-title":"Sensitivity of between-study heterogeneity in meta-analysis: proposed metrics and empirical evaluation","volume":"37","author":"Patsopoulos","year":"2008","journal-title":"Int J Epidemiol."},{"key":"B34","doi-asserted-by":"crossref","DOI":"10.1002\/sim.1761","article-title":"What to add to nothing? Use and avoidance of continuity corrections in meta-analysis of sparse data","volume":"23","author":"Sweeting","year":"2004","journal-title":"Stat Med"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1136\/bmj.315.7109.629","article-title":"Bias in meta-analysis detected by a simple, graphical test","volume":"315","author":"Egger","year":"1997","journal-title":"BMJ"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1607751","article-title":"Daratumumab, lenalidomide, and dexamethasone for multiple myeloma","volume":"375","author":"Dimopoulos","year":"2016","journal-title":"N Engl J Med"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1714678","article-title":"Daratumumab plus bortezomib, melphalan, and prednisone for untreated myeloma","volume":"378","author":"Mateos","year":"2018","journal-title":"N Engl J Med"},{"key":"B38","doi-asserted-by":"publisher","first-page":"29","DOI":"10.1016\/S0140-6736(19)31240-1","article-title":"Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study","volume":"394","author":"Moreau","year":"2019","journal-title":"Lancet."},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1182\/blood.2020005288","article-title":"Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial","volume":"136","author":"Voorhees","year":"2020","journal-title":"Blood."},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(21)00128-5","article-title":"Daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone alone in previously treated multiple myeloma (APOLLO): an open-label, randomised, phase 3 trial","volume":"22","author":"Dimopoulos","year":"2021","journal-title":"Lancet Oncol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1182\/bloodadvances.2023010026","article-title":"Final analysis of carfilzomib, dexamethasone, and daratumumab vs carfilzomib and dexamethasone in the CANDOR study","volume":"7","author":"Usmani","year":"2023","journal-title":"Blood Adv"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2312054","article-title":"Daratumumab, bortezomib, lenalidomide, and dexamethasone for multiple myeloma","volume":"390","author":"Sonneveld","year":"2024","journal-title":"N Engl J Med"},{"key":"B43","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1002\/9780470712184.ch10","article-title":"Addressing reporting biases","volume-title":"Cochrane Handbook for Systematic Reviews of Interventions","author":"Sterne","year":"2008"},{"key":"B44","doi-asserted-by":"publisher","first-page":"16","DOI":"10.1016\/j.imlet.2018.04.005","article-title":"Immunomodulatory effects of CD38-targeting antibodies","volume":"199","author":"van de Donk","year":"2018","journal-title":"Immunol Lett"},{"key":"B45","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/s41408-024-01107-6","article-title":"IgG replacement in multiple myeloma","volume":"14","author":"Wonnaparhown","year":"2024","journal-title":"Blood Cancer J"},{"key":"B46","doi-asserted-by":"crossref","DOI":"10.12998\/wjcc.v11.i29.7091","article-title":"Meta-analysis of the efficacy and safety of daratumumab in the treatment of multiple myeloma","volume":"11","author":"Wang","year":"2023","journal-title":"World J Clin Cases."},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2020.04.004","article-title":"Safety analysis of five randomized controlled studies of daratumumab in patients with multiple myeloma","volume":"20","author":"Al Hadidi","year":"2020","journal-title":"Clin Lymphoma Myeloma Leuk."}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1729177\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,6]],"date-time":"2026-01-06T05:18:19Z","timestamp":1767676699000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2025.1729177\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,6]]},"references-count":47,"alternative-id":["10.3389\/fonc.2025.1729177"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2025.1729177","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,6]]},"article-number":"1729177"}}