{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T05:28:21Z","timestamp":1761802101344,"version":"build-2065373602"},"reference-count":29,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,10,30]],"date-time":"2025-10-30T00:00:00Z","timestamp":1761782400000},"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:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Triplet regimens, such as bortezomib-lenalidomide-dexamethasone (VRd) and bortezomib-melphalan-prednisone (VMP), were standard treatments for newly diagnosed multiple myeloma (NDMM), but they were non-curative for most patients. The incorporation of daratumumab into these regimens, resulting in quadruplet therapies, has shown improved outcomes, though concerns over increased toxicity remain.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this systematic review and meta-analysis, we aimed to compare the efficacy and safety of daratumumab-incorporated quadruplet regimens versus traditional triplet regimens in NDMM. A search of PubMed, EMBASE, and the Cochrane Library identified six randomized controlled trials (RCTs) with 3,056 patients. Outcomes included response rates, minimal residual disease (MRD) negativity rate, progression-free survival (PFS), and adverse events.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with triplet regimens, daratumumab-incorporated quadruplet combinations achieved a higher overall survival rate (ORR) (pooled OR = 2.36, 95% CI: 1.56-3.56, P &amp;lt; 0.0001), rate of complete response (CR) or better (pooled OR = 2.35, 95% CI: 1.99-2.77, P &amp;lt; 0.0001), very good partial response (VGPR) or better (pooled OR = 2.58, 95% CI: 1.76-3.79, P &amp;lt; 0.0001) and MRD negativity (pooled OR = 3.55, 95% CI: 2.54-4.96, P &amp;lt; 0.0001). The addition of daratumumab to triplet regimens significantly improved PFS compared with triplet regimens (pooled HR = 0.45, 95% CI: 0.39\u20130.52, P &amp;lt; 0.0001). Regarding safety, quadruplet regimens were associated with a higher incidence of lymphopenia, upper respiratory tract infection, pyrexia, and pneumonia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Incorporating daratumumab into backbone triplet regimens is associated with improved response rates, deeper remission and prolonged PFS with acceptable toxicity profile in patients with NDMM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:uri>https:\/\/inplasy.com\/inplasy-2024-12-0026\/<\/jats:uri>\n                      , identifier INPLASY2024120026.\n                    <\/jats:p>\n                  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trials"],"prefix":"10.3389","volume":"15","author":[{"given":"Bin","family":"Hu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Fang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ling","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tianqi","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinxia","family":"Cao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,10,30]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2020.11.014","article-title":"Multiple myeloma: EHA-ESMO 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