{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T13:00:22Z","timestamp":1790686822313,"version":"4.1.0"},"reference-count":52,"publisher":"MDPI AG","issue":"19","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":[],"crossmark-restriction":false},"short-container-title":["Cancers"],"abstract":"<jats:p>Background: Several B-cell maturation antigen (BCMA)-directed therapy (BDT) modalities have been approved by the US Food and Drug Administration (FDA) for relapsed-refractory multiple myeloma (RRMM). Ideal sequencing of these therapies remains unknown. Methods: We report one of the largest multicenter retrospective patient cohorts in this real-world analysis of patients receiving a BDT in both BDT-na\u00efve and exposed settings at major academic centers. Results: In the BDT-na\u00efve setting, which included 276 patients, 169 (61%) received chimeric antigen receptor T-cell therapy (CAR-T), whereas 107 (39%) received bispecific antibodies (BsAbs). Median progression-free survival (PFS) in the BDT-na\u00efve setting was significantly longer with CAR-T than with BsAbs (16.1 vs. 13.5 months, p = 0.007) with a higher overall response rate (ORR) (87 vs. 68%). Multivariable Cox regression analysis revealed that receiving CAR-T (hazard ratio [HR] = 0.41), cytokine release syndrome (CRS) of any grade (HR = 0.50), achieving a best response of \u2265very good partial response (VGPR) (HR = 0.12), and high-risk cytogenetic abnormalities (HRCA) (HR = 2.29) were all significant prognostic indicators of PFS. Similarly, HRCA (HR = 2.32), CRS (HR = 0.36), and a best response of \u2265VGPR (HR = 0.16) were all independent prognostic factors of overall survival (OS). Of the 80 patients who received prior BDT, 22 received CAR-T (28%) and 58 (72%) received BsAbs. The median PFS was 6.3 months in the CAR-T group, with 64% ORR, vs. 4.4 months in the BsAb group, with 53% ORR (PFS HR, 0.93). Only the best response, \u2265VGPR (HR = 0.20), achieved significance in the multivariable model. Conclusions: CAR-T led to more durable responses in the BDT-na\u00efve setting than BsAbs. Responses to either modality were weaker in the BDT-exposed setting. These results highlight the importance of sequencing BDT in RRMM.<\/jats:p>","DOI":"10.3390\/cancers18193147","type":"journal-article","created":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:09:25Z","timestamp":1790683765000},"page":"3147","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sequencing BCMA-Directed Therapies in Relapsed\/Refractory Multiple Myeloma: A Real-World Comparison of CAR T-Cell Therapy and Bispecific Antibodies"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0004-1027-554X","authenticated-orcid":false,"given":"Osama M.","family":"Younis","sequence":"first","affiliation":[{"name":"School of Medicine, University of Jordan, Amman 11942, Jordan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sencer","family":"Goklemez","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology, University of Cincinnati, 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and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"given":"Andrew","family":"Vegel","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA 52242, USA"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0660-3446","authenticated-orcid":false,"given":"Emily","family":"Struble","sequence":"additional","affiliation":[{"name":"Division of Hematology, Oncology, and Blood & Marrow Transplantation, University of Iowa, Iowa City, IA 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