A phase 3 study observed “clinically remarkable” outcomes with the combination of teclistamab and daratumumab in patients with relapsed/refractory multiple myeloma (MM). At three years, 83.4% of patients were alive and progression-free.
Initial results from MajesTEC-3 were presented by María-Victoria Mateos, MD, PhD, of Hospital Universitario de Salamanca in Spain, as a late-breaking abstract at the 67th ASH Annual Meeting and Exposition.
Teclistamab is a BCMA×CD3 bispecific antibody, and daratumumab is a standard of care (SOC) CD38-targeted therapy used in MM.
The study included 587 patients (median age, 64 years) who received one to three prior lines of therapy, including a proteasome inhibitor and lenalidomide. All patients were naïve to BCMA-directed, and patients were not refractory to prior anti-CD38 therapy. Patients were randomized 1:1 to receive teclistamab plus daratumumab (n=291) or daratumumab, pomalidomide, and dexamethasone (DPd) or daratumumab, bortezomib, and dexamethasone (DVd) SOC combinations (n=296).
After 34.5 months of follow-up, teclistamab/daratumumab significantly improved progression-free survival (PFS) compared with DPd/DVd (P<0.0001), with 36-month PFS rates of 83.4% and 29.7%, respectively. This PFS benefit remained even in more difficult-to-treat patient populations, including patients who:
- Were aged ≥75 years
- Were lenalidomide-refractory
- Had high-risk cytogenetics
- Had ≥60% bone marrow plasma cells
- Had soft-tissue plasmacytomas
- Were anti-CD38 exposed
Patients in the teclistamab/daratumumab also had significantly higher rates of (P<0.0001):
- Complete response (81.8% vs 32.1%)
- Overall response (89.0% vs 75.3%)
- Measurable residual disease negativity (58.4% vs 17.1%)
The 36-month overall survival rates were 83.3% with teclistamab/daratumumab and 65.0% with DPd/DVd, and more than 90% of teclistamab/daratumumab-treated patients who were alive at six months remained alive at 30 months.
More deaths were reported in the DPd/DVd group (n=96 vs 45), primarily due to disease progression. Almost half of patients (49.4%) remained on study at data cutoff, with significantly more patients in the teclistamab/daratumumab group (71.0% vs 28.3%). Median treatment duration was twice as long in the teclistamab/daratumumab group (32.4 vs 16.1 months).
Serious adverse events occurred in both groups: 70.7% in the teclistamab/daratumumab arm and 62.4% in the DPd/DVd group. Infections also occurred often in both cohorts: 96.5% with teclistamab/daratumumab versus 84.1% with DPd/DVd. The researchers reported that infections were “well managed with establish protocols” involving antimicrobial and immunoglobulin prophylaxis.
Cytokine release syndrome occurred in 60.1% of patients in the teclistamab/daratumumab group, and immune effector cell–associated neurotoxicity syndrome was reported in 1.1% of patients.
“This highly effective, off-the-shelf, immunotherapy combination represents a new SOC for [relapsed/refractory] MM as early as first relapse,” the authors concluded.
Reference
Mateos MV, Bahlis N, Perrot A, et al. 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. Abstract LBA-6. Presented at the 67th American Society of Hematology Annual Meeting and Exposition; December 6-9, 2025; Orlando, Florida.
