{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T06:05:29Z","timestamp":1790661929119,"version":"4.1.0"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T00:00:00Z","timestamp":1790640000000},"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>Patients with relapsed\/refractory multiple myeloma (RRMM) experience poor outcomes following multiple lines of therapy. Available evidence has largely pooled disparate immunotherapy platforms. The present systematic review and meta-analysis was performed to describe, separately by target, the efficacy and toxicity spectra of BCMA\u00d7CD3-directed, GPRC5D\u00d7CD3-directed, and dual-target bispecific antibody therapy in RRMM, in order to inform toxicity monitoring and supportive-care planning.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The Cochrane Library, Embase, Web of Science, and PubMed were systematically searched up to January 28, 2026, to identify clinical trials and real-world studies evaluating GPRC5D\u00d7CD3 or BCMA\u00d7CD3 bispecific antibodies and their combinations for RRMM. Methodological quality was appraised with the Methodological Index for Non-Randomized Studies. Proportions and 95% confidence intervals (CIs) were pooled utilizing fixed-effects or random-effects models in R, selected according to heterogeneity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Twenty-seven studies\u2014comprising 13 single-arm clinical trials and 14 real-world investigations involving 4,045 patients\u2014met the inclusion criteria. The pooled objective response rate (ORR) for bispecific antibodies in RRMM was 65.54%. Target-stratified subgroup analysis yielded an ORR of 78.51% for GPRC5D\u00d7CD3 combined with BCMA\u00d7CD3, 69.67% for GPRC5D\u00d7CD3 alone, and 60.85% for BCMA\u00d7CD3 alone. The pooled minimal residual disease-negativity rate was 23.6%. Regarding safety, distinct antigen-specific toxicity spectra emerged across different targets. The BCMA\u00d7CD3 group exhibited elevated incidences of any-grade infection (56.37%) and grade 3\u20134 infection (26.37%), accompanied by pronounced hematological toxicity. The GPRC5D\u00d7CD3 group was characterized by epithelium-related toxicity: the incidence of grade 1\u20132 taste-related changes was 69.89%, that of any-grade nail-related adverse events (AEs) was 42.33%, and that of any-grade non-rash skin-related AEs was 58.3%; however, grade 3\u20134 nail-related AEs reached only 0.21%, and grade 3\u20134 non-rash skin-related AEs reached only 0.33%. The dual-target group bore a substantial burden of infection (84.53%) and hematological toxicity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Bispecific antibodies demonstrate clear antimyeloma activity in RRMM. BCMA\u00d7CD3-directed therapy is mainly related to infection and hematological toxicity, whereas GPRC5D\u00d7CD3-directed therapy is distinguished by epithelium-related toxicity, although severe events are rare.<\/jats:p>\n                  <\/jats:sec>\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                      identifier, CRD420261296139.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fimmu.2026.1937154","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T05:48:32Z","timestamp":1790660912000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and specific toxicity profiles of GPRC5D- versus BCMA-targeted bispecific antibodies in relapsed\/refractory multiple myeloma: a meta-analysis of clinical trials and real-world studies"],"prefix":"10.3389","volume":"17","author":[{"given":"Jiahao","family":"Ji","sequence":"first","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyu","family":"Zhao","sequence":"additional","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Wang","sequence":"additional","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayu","family":"Li","sequence":"additional","affiliation":[{"name":"Acupuncture, Tuina and Rehabilitation College, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fangliang","family":"Zhou","sequence":"additional","affiliation":[{"name":"Medical School, Hunan University of Chinese Medicine","place":["Changsha, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2022.0003","article-title":"Diagnosis and management of multiple myeloma: a review","volume":"327","author":"Cowan","year":"2022","journal-title":"Jama"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1007\/s00277-024-05730-y","article-title":"Therapeutic progress in relapsed\/refractory multiple myeloma","volume":"103","author":"Chen","year":"2024","journal-title":"Ann Hematol"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djae321","article-title":"The global multiple myeloma incidence and mortality burden in 2022 and predictions for 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