Background
Phase 1/2, open-label, single-arm trial (MajesTEC-1). N=165 (recommended phase 2 dose cohort) with relapsed or refractory multiple myeloma after ≥3 prior lines (median 5) including a PI, IMiD, and anti-CD38 antibody (triple-class exposed). Teclistamab is an off-the-shelf BCMAxCD3 bispecific antibody redirecting T cells to kill BCMA-expressing myeloma cells.
Interventions and follow up
Regimen: Teclistamab SC step-up 0.06 → 0.3 mg/kg, then 1.5 mg/kg SC weekly until progression or intolerance (BCMA × CD3 bispecific)
Population: Triple-class–exposed R/R MM
Primary endpoint: Overall response rate (ORR)
mFollow up: 14.1 months
Population: Triple-class–exposed R/R MM
Primary endpoint: Overall response rate (ORR)
mFollow up: 14.1 months
Results
ORR: 63.0% (95% CI 54.9–70.6%)
≥CR rate: 39.4%
MRD-negativity (10⁻⁵, among ≥CR): 46%
mDOR: 18.4 months
mPFS: 11.3 months
≥CR rate: 39.4%
MRD-negativity (10⁻⁵, among ≥CR): 46%
mDOR: 18.4 months
mPFS: 11.3 months
Adverse events
CRS/neurotoxicity: CRS any grade 72.1%, grade ≥3 0.6%; ICANS any grade 14.5%, grade ≥3 3.0%
Infections: Any grade 76.4%, grade ≥3 44.8% (including opportunistic infections)
Hematologic: Neutropenia grade ≥3 64.2%; step-up dosing required inpatient monitoring
Infections: Any grade 76.4%, grade ≥3 44.8% (including opportunistic infections)
Hematologic: Neutropenia grade ≥3 64.2%; step-up dosing required inpatient monitoring
Conclusions
Teclistamab achieved a 63% ORR with 39% ≥CR in triple-class-exposed RRMM — the first off-the-shelf BCMA-directed bispecific antibody to show efficacy in this setting — with predominantly low-grade CRS and durable responses, representing a major advance for patients without access to or ineligible for CAR-T.
Key Limitations
Single-arm design without a randomized comparator. High rates of grade ≥3 and opportunistic infections (including PJP, CMV) reflect deep, prolonged hypogammaglobulinemia and require IVIG support and antimicrobial prophylaxis. Continuous weekly dosing imposes ongoing treatment burden and infection surveillance. Step-up dosing mandates inpatient or close monitoring for CRS.
Clinical Context
FDA granted accelerated approval to teclistamab (Tecvayli) in October 2022 for RRMM after ≥4 prior lines; EMA approved it the same year. It was the first bispecific antibody approved for myeloma. Infection prophylaxis and IVIG are now standard supportive care. ESMO-MCBS reflects meaningful benefit in a heavily pretreated population.