{ "abstract": "Background: Triplet and quadruplet regimens have greatly improved outcomes in newly diagnosed multiple myeloma, yet a high unmet need remains for more effective, broadly accessible treatments for anti-CD38- and lenalidomide- (Len) exposed/refractory RRMM. Teclistamab (Tec) is the most widely used BCMA×CD3 BsAb in heavily pretreated RRMM, with improved outcomes in earlier lines of therapy (LOTs). In MajesTEC-3, the synergistic Tec-daratumumab combination significantly improved progression-free and overall survival (PFS/OS) as early as first relapse. MajesTEC-9 (NCT05572515) is the first phase 3 study of Tec monotherapy in pts with 1–3 prior LOTs. Methods: Pts with RRMM and 1–3 prior LOTs including anti-CD38 and Len were randomized 1:1 to receive 28-day cycles (C) of Tec (C1–2: 2 step-up doses then 1.5 mg/kg QW; C3–6: 3 mg/kg Q2W or Q4W depending on response; C7+: 3 mg/kg Q4W) or investigator’s choice of PVd/Kd (21/28-day C). Primary endpoint was PFS by IRC; secondary endpoints included OS, complete response or better (≥CR), and safety. Results: 593 pts were randomized (Tec, n=296; PVd/Kd, n=297). Median (range) age: 70 (34–86) yrs; number of prior LOTs: 2 (1–3); Len refractory: 80%; anti-CD38 refractory: 85%; refractory to last LOT: 92%. With 17.3-mo median follow-up, Tec significantly improved PFS vs PVd/Kd (HR, 0.29; 95% CI, 0.23–0.38; P<0.0001); mPFS: NR vs 8.2 mo; 18-mo PFS rate: 69.8% vs 26.9%. OS was significantly improved with Tec vs PVd/Kd (HR, 0.60; 95% CI, 0.43–0.83; P=0.0020). Of 174 PVd/Kd pts who received subsequent treatment, 68.4% received BsAb or CAR-T. PFS favored Tec across all prespecified subgroups, including anti-CD38-refractory pts and Len-refractory pts. ≥CR rate was significantly higher with Tec vs PVd/Kd (65.9% vs 16.8%; OR, 10.42; 95% CI, 6.89–15.76; P<0.0001). At data cutoff, 65.3% of pts remained on Tec vs 24.0% on PVd/Kd (safety set: Tec, n=291; PVd/Kd, n=283). TEAEs were similar for Tec and PVd/Kd (99.7% vs 97.9%). Grade (Gr) 3/4 TEAEs (84.9% vs 76.3%) and Gr 5 TEAEs (6.5% vs 3.5%) were higher with Tec vs PVd/Kd, noting the median treatment duration was nearly doubled with Tec (13.1 vs 7.0 mo). Treatment discontinuation due to TEAEs was lower with Tec vs PVd/Kd (10.7% vs 13.1%). Gr 3/4 infections were higher with Tec vs PVd/Kd (41.6% vs 29.0%). Any-onset Gr ≥3 infections decreased over time. CRS occurred in 66.0% of pts with Tec (Gr 1/2: 48.8%/16.5%) and ICANS in 4.1% (Gr 1/2: 2.4%/1.4%). Conclusions: Tec monotherapy significantly improved PFS/OS vs standard of care (SoC) in this high unmet need population. CRS and infections were managed with established protocols. Results of phase 3 studies support Tec-based regimens as a SoC as early as second line, across all treatment settings and regardless of prior anti-CD38/Len exposure. Acknowledgments: This study was funded by Johnson & Johnson.", "abstract_shown": true, "affiliations": [ "Winship Cancer Institute, Emory University, Atlanta, United States", "Department of Hematology, University Hospital of Nantes, Nantes, France", "Clínica Médica São Germano, São Paulo, São Paulo, SP, Brasil", "Myeloma Division, Sylvester Comprehensive Cancer Center, University of Miami, Miami, FL, United States", "Division of Hematology/Oncology, Columbia University Medical Center, New York, United States", "Department of Hematology, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China", "Division of Hematology and Oncology, Neag Comprehensive Cancer Center, University of Connecticut Health, Farmington, United States", "Department of Hematology and Oncology, Myeloma and Amyloidosis Program, Cleveland Clinic Florida, FL, United States", "Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece", "Arnie Charbonneau Cancer Research Institute, University of Calgary, Calgary, Canada", "Department of Hematology, Faculty of Medicine, Istanbul Medipol University, Istanbul, Türkiye", "Department of Hematology, Amsterdam University Medical Center, Cancer Center Amsterdam, Netherlands", "Hematology Department, Colchester Hospital, East Suffolk and North Essex NHS Foundation Trust, Colchester, United Kingdom", "Department of Internal Medicine I, University Hospital Dresden, Technical University Dresden, Dresden, Germany", "Department of Hematology, Juntendo University School of Medicine, Tokyo, Japan", "Johnson & Johnson, Raritan, NJ, United States", "Johnson & Johnson, Spring House, PA, United States", "Johnson & Johnson, High Wycombe, United Kingdom", "A.C.Camargo Cancer Center in São Paulo, São Paulo, SP, Brazil" ], "article_type": null, "arxiv": null, "author_total": 20, "authors": [ { "affs": [ 0 ], "name": "Roberto MINA" }, { "affs": [ 1 ], "name": "Cyrille TOUZEAU" }, { "affs": [ 2 ], "name": "Vania HUNGRIA" }, { "affs": [ 3 ], "name": "Ola LANDGREN" }, { "affs": [ 4 ], "name": "Divaya BHUTANI" }, { "affs": [ 5 ], "name": "Wenming CHEN" }, { "affs": [ 6 ], "name": "Swarup KUMAR" }, { "affs": [ 7 ], "name": "Chakra P CHAULAGAIN" }, { "affs": [ 8 ], "name": "Meletios A DIMOPOULOS" }, { "affs": [ 9 ], "name": "Nizar BAHLIS" }, { "affs": [ 10 ], "name": "Senem MARAL" }, { "affs": [ 11 ], "name": "Niels W.C.J. VAN DE DONK" }, { "affs": [ 12 ], "name": "Khalid SAJA" }, { "affs": [ 13 ], "name": "Raphael TEIPEL" }, { "affs": [ 14 ], "name": "Miki ANDO" }, { "affs": [ 15 ], "name": "Dai WANG" }, { "affs": [ 16 ], "name": "Susan WROBLEWSKI" }, { "affs": [ 17 ], "name": "Priya SHAH" }, { "affs": [ 15 ], "name": "Katherine CHASTAIN" }, { "affs": [ 18 ], "name": "Jayr SCHMIDT" } ], "bibtex": "https://research.draconitic.com/paper/4pgwa8yph7c0c.bib", "cited_by": 0, "doi": "10.1016/j.htct.2026.107889", "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S2531137926016366", "id": "4pgwa8yph7c0c", "issns": [ "2531-1379", "2531-1387" ], "landing_url": "https://doi.org/10.1016/j.htct.2026.107889", "language": "en", "licence": "CC-BY", "licence_label": "CC BY", "licence_source": "journal", "licence_url": "https://creativecommons.org/licenses/by/4.0/", "metadata_licence": null, "native_subjects": [ [ "lcc", "RC633-647.5" ], [ "openalex", "2720|Multiple Myeloma Research and Treatments" ] ], "openalex": "W7223103317", "pdf_url": null, "pmcid": null, "pmid": null, "published": "2026-10-23", "publisher": "Elsevier", "ris": "https://research.draconitic.com/paper/4pgwa8yph7c0c.ris", "sources": [ { "first_seen": "2026-10-30T13:43:26Z", "native_id": "94c9f973b2364b44a12cd4797b184552", "source": "doaj", "url": "https://doi.org/10.1016/j.htct.2026.107889" } ], "subjects": [ { "field": "medicine", "origin": "lcc:RC633-647.5", "subfield": "endocrinology-metabolism" } ], "title": "MAJESTEC-9: A PHASE 3 RANDOMIZED STUDY OF TECLISTAMAB MONOTHERAPY VS INVESTIGATOR’S CHOICE OF POMALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE OR CARFILZOMIB AND DEXAMETHASONE (PVD/KD) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM)", "title_text": "MAJESTEC-9: A PHASE 3 RANDOMIZED STUDY OF TECLISTAMAB MONOTHERAPY VS INVESTIGATOR’S CHOICE OF POMALIDOMIDE, BORTEZOMIB, AND DEXAMETHASONE OR CARFILZOMIB AND DEXAMETHASONE (PVD/KD) IN PATIENTS (PTS) WITH RELAPSED REFRACTORY MULTIPLE MYELOMA (RRMM)", "type": "peer-reviewed", "updated_at": "2026-10-30T13:43:26Z", "url": "https://research.draconitic.com/paper/4pgwa8yph7c0c", "venue": "Hematology, Transfusion and Cell Therapy", "versions": [] }