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Shaji K. Kumar, MD
Shaji K. Kumar, MD
Posted: Friday, December 12, 2025
The combination of teclistamab, a BCMAxCD3 bispecific antibody, plus daratumumab demonstrated “remarkable” improvement in both progression-free survival and overall survival compared with standard-of-care triplets in patients with relapsed or refractory multiple myeloma, according to results from the phase III MajesTEC-3 trial presented as a late-breaking abstract during the 2025 American Society of Hematology (ASH) Annual Meeting. This study represents the first phase III trial of bispecific antibody therapy in multiple myeloma.
The MajesTEC-3 trial enrolled 587 patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy, including a proteasome inhibitor and lenalidomide, and progressive disease on or after the last line of therapy. Patients were randomized to receive either teclistamab plus daratumumab or investigator's choice of daratumumab with pomalidomide/dexamethasone or bortezomib/dexamethasone.
With a median follow-up of 34.5 months, teclistamab-daratumumab significantly improved progression-free survival compared with standard-of-care triplets, with median progression-free survival not reached vs 18.1 months (hazard ratio [HR] = 0.17; 95% confidence interval [CI] = 0.12–0.23; P < .0001). The 36-month progression-free survival rate was 83.4% with teclistamab/daratumumab vs 29.7% with the triplet regimens.
Overall survival also significantly favored teclistamab/daratumumab, with 36-month overall survival rates of 83.3% and 65.0%, respectively (HR = 0.46; 95% CI = 0.32-0.65; P < .0001). Complete response or better was achieved in 81.8% of patients receiving teclistamab/daratumumab compared with 32.1% receiving standard of care. In the teclistamab/daratumumab arm, 83.4% of patients were still alive and progression-free at 3 years.
Grade 3/4 treatment-emergent adverse events occurred in 95.1% and 96.6% of patients in the teclistamab/daratumumab and standard-of-care arms, respectively; with grade 5 events reported in 7.8% and 6.2% of patients in each arm. Cytokine release syndrome occurred in 60.1% of teclistamab/daratumumab patients but was predominantly grade 1/2. New onset grade 3 or higher infections decreased over time with transition to every-4-week dosing and with prophylaxis.
"This highly effective, off-the-shelf, immunotherapy combination represents a new standard of care for relapsed/refractory multiple myeloma as early as first relapse," the study authors, led by María-Victoria Mateos, MD, PhD, Associate Professor of Medicine and Director of the Myeloma Program at Salamanca University Hospital in Spain, concluded in the abstract.
Disclosure: The study was funded by Johnson & Johnson. For full disclosures of the study authors, visit meetings-api.hematology.org.
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