{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T11:01:00Z","timestamp":1777633260142,"version":"3.51.4"},"reference-count":64,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T00:00:00Z","timestamp":1777420800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100003787","name":"Natural Science Foundation of Hebei Province","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100003787","id-type":"DOI","asserted-by":"publisher"}]}],"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>Relapsed\/refractory multiple myeloma (RRMM) remains a clinical challenge despite therapeutic advances. CD38-directed chimeric antigen receptor T-cell (CAR-T) therapy, especially dual-target CD38\/BCMA constructs, represents an emerging immunotherapeutic strategy. This systematic review and meta-analysis aimed to evaluate the efficacy and safety of CD38-directed CAR-T in RRMM.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We systematically searched Medline, Embase, and Cochrane Library up to October 1, 2025. Eligible clinical trials investigating CD38-directed CAR-T (single-target or dual-target CD38\/BCMA) for RRMM were included. Random-effects model was used to pool efficacy and safety outcomes of dual-target studies, while single-target CD38 data were summarized descriptively.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>A total of 4 studies involving 70 patients were included (3 dual-target CD38\/BCMA studies, n=61; 1 single-target CD38 study, n=9). For dual-target CD38\/BCMA CAR-T, the pooled overall response rate (ORR) was 89% (95% CI: 81%\u201397%), complete response\/stringent complete response (CR\/sCR) rate was 63% (95% CI: 44%\u201382%), and minimal residual disease (MRD)-negative rate was 67%. Mortality was 11%. The single-target CD38 CAR-T showed lower efficacy (ORR\u00a0=\u00a033%) and higher mortality (44%). Any-grade cytokine release syndrome (CRS) occurred in 83% of patients, with grade \u22653 CRS in 26%. Other adverse events included infections (23%), immune effector cell-associated neurotoxicity syndrome (ICANS, 13%), and kidney injury (13%).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Dual-target CD38\/BCMA CAR-T demonstrates promising efficacy and manageable safety in RRMM. Evidence for single-target CD38 CAR-T remains limited and requires cautious interpretation. Further large-scale comparative studies are warranted to determine the optimal role of CD38-directed CAR-T in RRMM treatment sequencing.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fonc.2026.1744250","type":"journal-article","created":{"date-parts":[[2026,4,29]],"date-time":"2026-04-29T04:32:14Z","timestamp":1777437134000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of CD38-directed CAR-T cell therapy for multiple myeloma: a systematic review and meta-analysis"],"prefix":"10.3389","volume":"16","author":[{"given":"Xinlong","family":"Xu","sequence":"first","affiliation":[{"name":"Graduate School, Hebei North University","place":["Zhangjiakou, China"]},{"name":"Department of Hematology, Hebei General Hospital","place":["Shijiazhuang, 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