Background
Phase 3, open-label RCT; N=593; relapsed/refractory multiple myeloma after 1–3 prior lines including an anti-CD38 monoclonal antibody and lenalidomide; teclistamab is a BCMA×CD3 bispecific antibody; randomized (296 vs 297).
Results
Interventions and follow up: Arm A: Teclistamab SC monotherapy (weekly after step-up dosing); antimicrobial prophylaxis + IV immunoglobulin replacement recommended (n=296)
Arm B: Investigator's choice — pomalidomide–bortezomib–dexamethasone (PVd) or carfilzomib–dexamethasone (Kd) (n=297)
Primary endpoint: PFS by independent review committee
mFollow up: 17.3 mo (interim analysis)
Results: PFS (18-mo): 69.8% vs 26.9%; HR 0.29 (95% CI 0.23–0.38); P<.001
≥CR: 65.9% vs 16.8%; P<.001
OS (18-mo): 79.2% vs 68.6%; HR 0.60 (95% CI 0.43–0.83); P=.002
Arm B: Investigator's choice — pomalidomide–bortezomib–dexamethasone (PVd) or carfilzomib–dexamethasone (Kd) (n=297)
Primary endpoint: PFS by independent review committee
mFollow up: 17.3 mo (interim analysis)
Results: PFS (18-mo): 69.8% vs 26.9%; HR 0.29 (95% CI 0.23–0.38); P<.001
≥CR: 65.9% vs 16.8%; P<.001
OS (18-mo): 79.2% vs 68.6%; HR 0.60 (95% CI 0.43–0.83); P=.002
Adverse events
Grade 3/4 (any): 84.9% vs 76.3%
Grade 5 (fatal): 6.5% vs 3.5%
CRS: 66.0% (mostly grade 1/2)
ICANS: 4.1%
Grade 3/4 infection: 41.6% vs 29.0%
Grade 5 (fatal): 6.5% vs 3.5%
CRS: 66.0% (mostly grade 1/2)
ICANS: 4.1%
Grade 3/4 infection: 41.6% vs 29.0%
Conclusions
In relapsed/refractory multiple myeloma after 1–3 prior lines (anti-CD38 and lenalidomide exposed), teclistamab monotherapy significantly improved PFS and OS vs PVd/Kd with deep responses (≥CR 65.9%). Moves the off-the-shelf BCMA bispecific from late-line into earlier relapse; grade 3/4 infections were common and CRS mostly low-grade.
Key Limitations
Open-label design; interim analysis (median follow-up 17.3 mo); investigator's-choice comparator (PVd/Kd doublet/triplet) may underperform vs contemporary anti-CD38–based regimens; high grade 3/4 infection (41.6%) and CRS (66%) require prophylaxis, IVIG and step-up monitoring; no head-to-head vs BCMA CAR-T.
Clinical Context
Teclistamab (Tecvayli, Johnson & Johnson) is FDA/EMA approved for RRMM after ≥4 prior lines (triple-class–exposed; MajesTEC-1). MajesTEC-9 is the registrational phase 3 supporting use as early as first relapse (1–3 prior lines). If approved in this setting it positions an off-the-shelf BCMA bispecific against standard PVd/Kd at early relapse, paralleling the earlier-line moves of BCMA CAR-T (CARTITUDE-4, KarMMa-3). Presented at ASCO 2026 and published in NEJM.