relapsed/refractory multiple myeloma bi-specific antibody: big benefits
María-Victoria Mateos; ASH 2025: Unprecedented Survival Benefits with BCMA/CD3 Bispecific Antibody Teclistamab in Patients with Relapsed or Refractory Multiple Myeloma: Majestec-3 Study Findings
An interview with:
María-Victoria Mateos MD PhD, Hematologist and Myeloma Unit Director, Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, and Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain.
ORLANDO, USA—Statistically significant improvements in progression-free and overall survival among patients with relapsed or refractory multiple myeloma were reported at the 2025 Annual Meeting of the American Society of Hematology. The addition of the B-cell maturation antigen/CD3 bispecific antibody teclistamab to standard second-line therapies, brought “clinically remarkable” benefits in the majestec-3 study.
The first author María-Victoria Mateos MD PhD, Hematologist and Myeloma Unit Director at the University Hospital of Salamanca in Spain, gave the details to Audio Journal of Oncology reporter, Peter Goodwin:
AUDIO JOURNAL OF ONCOLOGY: María-Victoria Mateos MD PhD
IN: [GOODWIN] “Peter Goodwin here at the American …….
OUT: …..I’m Peter Goodwin 8:01 secs
From: ASH 2025
Publication Number: LBA-6
Abstract Title : Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or Bortezomib (DPd/DVd) in patients (Pts) with relapsed refractory multiple myeloma (RRMM): Results of majestec-3
María-Victoria Mateos
1Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain
Blood (2025) 146 (Supplement 2): LBA-6.
https://doi.org/10.1182/blood-2025-LBA-6
AUTHORS:
María-Victoria Mateos1, Nizar Bahlis2, Aurore Perrot3, Ajay Nooka4, Jin Lu5, Charlotte Pawlyn6, 7, Roberto Mina8, Gaston Caeiro9, Alain Kentos10, Vania
Hungria11, Donna Reece12, Ting Niu13, Anne Mylin14,Charlotte Hansen15, Raphael Teipel16, Britta Besemer17, Meletios Dimopoulos18, 19, Elena Zamagni20, 21,
Satoshi Yoshihara22, Kihyun Kim23, Chang-Ki Min24, Paulus Geerts25, Elena Van Leeuwen-Segarceanu26, Agata Tyczynska27, Juan Luis Reguera28, Magnus Johansson29, Markus Hansson30, Mehmet Turgut31,Mark Grey32, Surbhi Sidana33, Paula Rodriguez-Otero34, Joaquin Martinez-Lopez35, Hamza Hashmi36, Robin Carson37, Rachel Kobos38, Weili Sun39, Kristen Lantz37, Anne Seifert40, Debbie Briseno-Toomey41, Lisa O’Rourke37, Maria Rubin38, Diego Vieyra37, Lijuan Kang39, Luciano Costa42
INSTITUTIONS
1 Hospital Universitario de Salamanca, Instituto de Investigación Biomédica de Salamanca, Instituto de Biología Molecular y Celular del Cáncer (Universidad de Salamanca-Consejo Superior de Investigaciones Científicas), CIBERONC, Salamanca, Spain,
2 Arnie Charbonneau Cancer Institute, University of Calgary, Calgary, AB, Canada, 3 Universite de Toulouse, Centre Hospitalier Universitaire, Service d’Hematologie,
IUCT Oncopole CRCT, Toulouse, France,
4 Emory University, Winship Cancer Institute, Atlanta, GA, United States,
5 Peking University People’s Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing, China,
6 The Royal Marsden NHS Foundation Trust, London, United Kingdom,
7 The Institute of Cancer Research, London, United Kingdom,
8 Division of Hematology, Department of Molecular Biotechnology and Health Sciences, AOU Città della Salute e della Scienza di Torino, University of Torino, Torino, Italy,
9 Hospital Privado Centro Medico de Córdoba SA, Córdoba, Argentina,
10 Department of Hematology, Hôpital de Jolimont, Haine-Saint-Paul, Belgium,
11 Clinica São Germano, São Paulo, Brazil, 12 Princess Margaret Cancer Centre, Toronto, ON, Canada,
13 Department of Hematology, West China Hospital, Sichuan University, Chengdu, China,
14 Department of Hematology, Rigshospitalet, Copenhagen, Denmark,
15 Department of Hematology, Odense University
Hospital, Odense, Denmark,
16 Medizinische Klinik und Poliklinik I Universitätsklinikum Carl Gustav Carus
an der Technischen Universität Dresden, Dresden, Germany,
17 Department of Internal Medicine II, University Tübingen, Tübingen, Germany,
18 Department of Clinical Therapeutics, National and Kapodistrian University of Athens, School of Medicine, Athens, Greece,
19 Department of Medicine, Korea University, Seoul, Korea, Rep. of South,
20 IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di
Ematologia “Seràgnoli”, Bologna, Italy,
21 Dipartimento di Scienze Mediche e Chirurgiche, Università di Bologna, Bologna, Italy,
22 Department of Hematology, Hyogo Medical University Hospital, Nishinomiya,
Japan,
23 Division of Hematology-Oncology, Department of Medicine, Sungkyunkwan University School of Medicine, Samsung Medical Center, Seoul, Korea, Dem. People´s Rep. of,
24 Department of Hematology, College of Medicine, Seoul St. Mary’s Hospital, The Catholic University of Korea, Seoul, Korea, Dem. People´s Rep. of,
25 Department of Internal Medicine, Isala Klinieken, Zwolle, Netherlands,
26 Department of Hematology, St. Antonius Hospital Nieuwegein, Nieuwegein, Netherlands,
27 Department of Hematology and Transplantology, Medical University of Gdansk; Department of Hematology and Transplantology, University Clinical Center, Gdansk, Poland,
28 Department of Hematology, University Hospital Virgen del Rocío, Instituto de Biomedicina de la Universidad de Sevilla, Seville, Spain,
29 Medicinkliniken, Sunderby Sjukhus, Luleå, Sweden,
30 Sahlgrenska University Hospital, Göteborg, Sweden,
31 Department of Internal Medicine, Division of Hematology, Ondokuz Mayis University, Samsun Türkiye,
32 The Lancashire Haematology Centre, Blackpool Teaching Hospitals NHS Foundation Trust, Blackpool Victoria Hospital, Blackpool, United Kingdom,
33 Stanford University School of Medicine, Palo Alto, CA, United States,
34 Cancer Center Clínica Universidad de Navarra, University of Navarra,
Pamplona, Spain,
35 Hematology Department, Hospital 12 de Octubre, i+12, Universidad Complutense, MIC, Centro Nacional de Investigaciones Oncológicas, CIBERONC, Madrid, Spain,
36 Memorial Sloan Kettering Cancer Center, New York, NY, United States,
37 Johnson & Johnson, Spring House, PA, United States,
38 Johnson & Johnson, Raritan, NJ, United States,
39 Johnson & Johnson, Los Angeles, CA, United States,
40 Johnson & Johnson, High Wycombe, United Kingdom,
41 Johnson & Johnson, Yorba Linda, CA, United States,
42 Division of Hematology and Oncology, University of Alabama at Birmingham,
Birmingham, AL, United States
ABSTRACT:
Introduction: In RRMM, increasing rates of pt attrition and decreasing durability of responses with each line of therapy (LOT) necessitate early treatment (tx) with the most effective therapies. Immunotherapies that are widely accessible across different MM tx settings have the potential to change the trajectory of RRMM.
Teclistamab (Tec), the first approved BCMA×CD3 bispecific antibody (BsAb) for heavily pretreated RRMM, provided deep, durable responses in MajesTEC-1, with improved efficacy and safety in earlier LOTs. Daratumumab (Dara), a standard-of-care (SoC) foundational CD38 targeted therapy with direct on-tumor activity, has been shown to deplete immunosuppressive T-cells and expand cytotoxic T-cells, creating an immune-permissive microenvironment for synergistic Tec-mediated killing of MM cells. MajesTEC-3 (NCT05083169) evaluates Tec-Dara vs SoC DPd/DVd in RRMM. We report initial results for this first phase 3 study of BsAb therapy in MM.
Methods: Eligible pts had 1-3 prior LOTs including a PI and lenalidomide (Len; pts with 1 prior LOT must have been Len-refractory) with progressive disease (PD) on or after the last LOT. Pts with prior BCMA-directed therapy or refractory to anti-CD38 were excluded; prior anti-CD38 exposure was permitted. Pts were randomized 1:1 to Tec-Dara or DPd/DVd. The Tec-Dara group received 28-day cycles (C) of Tec (1.5 mg/kg QW in C1-2 [C1 preceded by the approved step-up dose schedule]; 3 mg/kg Q2W in C3-6; and 3 mg/kg Q4W in C7+) with Dara; steroids were not required after C1 Day 8. Tec and Dara dosing were aligned with the approved Dara schedule. DPd/DVd were administered per approved schedules. Progression-free survival (PFS) by IRC was the primary endpoint; secondary endpoints included complete response or better (≥CR), overall response, minimal residual disease (MRD) negativity (10–5; next-generation sequencing), overall survival (OS), time to worsening of symptoms (MySIm-Q), and safety.
Results: 587 pts were randomized (Tec-Dara, n=291; DPd/DVd, n=296). Median (range) age was 64 (25-88) yrs, median number of prior LOTs was 2 (1-3). With 34.5-mo median follow-up, Tec-Dara significantly improved PFS vs DPd/DVd (HR, 0.17; 95% CI, 0.12-0.23; P<0.0001); mPFS was NR and 18.1 mo, and 36-mo PFS rate was 83.4% and 29.7%, respectively. PFS benefit was consistent across all prespecified and clinically relevant pt subgroups, including age ≥75 yrs, Len-refractory, high-risk cytogenetics, ≥60% bone marrow plasma cells, soft-tissue plasmacytomas, and anti-CD38 exposed. Significantly higher rates of ≥CR (81.8% vs 32.1%; OR, 9.56; 95% CI, 6.47-14.14), overall response (89.0% vs 75.3%; OR, 2.65; 95% CI, 1.68-4.18), and MRD-negativity (58.4% vs 17.1%; OR, 6.78; 95% CI, 4.53-10.15) were observed with Tec-Dara (P<0.0001). There were 45 deaths with Tec-Dara and 96 with DPd/DVd, primarily due to PD (4.6%; 20.3%). OS significantly favored Tec-Dara (HR, 0.46; 95% CI, 0.32-0.65; P<0.0001), including across all prespecified subgroups. The 36-mo OS rates were 83.3% and 65.0%, respectively and >90% of Tec-Dara pts alive at 6 mo were also alive at 30 mo. Median time to worsening of MM symptoms was NR with Tec-Dara vs 39.9 mo with DPd/DVd (HR, 0.50; 95% CI, 0.34-0.72; P=0.0002).
At data cutoff, 49.4% of pts remained on study tx (Tec-Dara, 71.0%; DPd/DVd, 28.3%). Median tx duration was twice as long with Tec-Dara vs DPd/DVd (32.4 vs 16.1 mo). Frequency of grade 3/4 (Tec-Dara, 95.1%; DPd/DVd, 96.6%) and grade 5 (7.8%; 6.2%) treatment-emergent adverse events (TEAEs), were comparable (safety set: Tec-Dara, n=283; DPd/DVd, n=290). Serious TEAEs occurred in 70.7% Tec-Dara and 62.4% DPd/DVd pts; tx discontinuations due to TEAEs were low (4.6% vs 5.5%). Any grade infections occurred in 96.5% and 84.1% of Tec-Dara and DPd/DVd pts, respectively; grade 3/4 infections occurred in 54.1% and 43.4%. New onset grade ≥3 infections decreased over time, coinciding with transition to Q4W dosing and supported by antimicrobial and Ig prophylaxis guidance. CRS rate was 60.1% (grade 1/2: 44.2%/15.9%) and ICANS was 1.1% with Tec-Dara.
Conclusion: We demonstrate the clinically remarkable and statistically significant PFS and OS benefits of Tec-Dara vs SoC triplets in RRMM, with 83.4% of Tec-Dara pts alive and progression-free at 3 yrs. Infections with Tec-Dara were well managed with established protocols. This highly effective, off-the-shelf, immunotherapy combination represents a new SoC for RRMM as early as first relapse.
María-Victoria Mateos MD PhD AJO TEXT 13 February, 2026