{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T05:42:39Z","timestamp":1793943759684,"version":"4.8.0"},"reference-count":38,"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. Immunol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The efficacy of CD38 monoclonal antibody (mAb)-based quadruplet regimens versus triplet regimens in newly diagnosed multiple myeloma (NDMM) patients with high-risk cytogenetics remains controversial. This meta-analysis aims to consolidate evidence from randomized controlled trials (RCTs) to resolve this clinical uncertainty.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We systematically searched PubMed, EMBASE, and the Cochrane Library for RCTs comparing CD38 mAb-based quadruplet regimens with triplet regimens in NDMM patients with high-risk cytogenetics. The primary outcomes were the rate of minimal residual disease (MRD) negativity at a sensitivity of 10\n                      <jats:sup>-5<\/jats:sup>\n                      and progression-free survival (PFS).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Nine RCTs comprising 4557 patients were included. Compared to triplet regimens, CD38 mAb-based quadruplet regimens were associated with a significantly higher rate of MRD negativity (pooled OR = 2.02, 95% CI: 1.41-2.88, P = 0.0001) and a significantly improved PFS (pooled HR = 0.74, 95% CI: 0.59-0.94, P = 0.01). However, subgroup analyses revealed that the PFS benefit was not significant for isatuximab-based quadruplet regimens (pooled HR = 1.04, 95% CI: 0.67-1.62, P = 0.84) or in transplant-ineligible patients (pooled HR = 0.79, 95% CI: 0.56-1.13, P = 0.19).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The incorporation of CD38 mAbs, particularly daratumumab, into triplet regimens improves depth of response and PFS in NDMM patients with high-risk cytogenetics.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Systematic review registration<\/jats:title>\n                    <jats:p>\n                      <jats:ext-link>https:\/\/inplasy.com\/inplasy-2025-10-0103\/<\/jats:ext-link>\n                    <\/jats:p>\n                    <jats:p>, identifier INPLASY2025100103.<\/jats:p>\n                  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