MajesTEC-9: Teclistamab Monotherapy Delivers Survival Benefits in Early Relapsed/Refractory Multiple Myeloma

Sawyer Bawek, DO University at Buffalo

Key Points

• Teclistamab monotherapy significantly improved progression-free survival (PFS) vs PVd/Kd in patients with relapsed/refractory multiple myeloma after 1–3 prior lines of therapy.

• Treatment with teclistamab was associated with a 40% reduction in the risk of death and substantially higher ≥CR rates compared with standard regimens.

• Although efficacy was robust across subgroups, higher rates of grade 3/4 infections and the need for step-up dosing and monitoring remain key clinical considerations.

In the rapidly advancing field of multiple myeloma, T-cell–redirecting therapies continue to show robust efficacy in progressively earlier lines of therapy. Ahead of the 2026 American Society of Clinical Oncology (ASCO) Annual Meeting,  phase 3 data from MajesTEC-9 to be presented later this week show compelling support for teclistamab monotherapy in patients with relapsed/refractory multiple myeloma (RRMM)after previous therapy. 

MajesTEC-9: Teclistamab Monotherapy vs Investigator’s Choice

The phase 3 MajesTEC-9 trial (NCT05572515) evaluated teclistamab, a BCMA×CD3 bispecific antibody, as monotherapy versus investigator’s choice of pomalidomide-bortezomib-dexamethasone (PVd) or carfilzomib-dexamethasone (Kd). The study enrolled patients with RRMM who had received 1 to3 prior lines of therapy, including prior exposure to an anti-CD38 monoclonal antibody and lenalidomide. 

Key Results:

• Significant improvement in progression-free survival (PFS) for teclistimab monotherapy compared with PVd or Kd (HR, 0.29; 95% CI, 0.23–0.38) with median PFS not reached for Tec versus 8.2 months for standard of care. The 18-month PFS rate was 69.8% versus 26.9%. 
• 40% reduction in the risk of death for teclistimab versus PVd/Kd (HR, 0.60).
• Benefit was observed across subgroups, including anti-CD38–refractory and lenalidomide-refractory patients 
•  ≥CR rate was significantly higher with teclistimab vs PVd/Kd (65.9% vs 16.8%)

Safety Profile: 

• 65.3% of patients remained on tec at data cutoff compared with 24% on PVd/Kd
• Grade 3/4 treatment-emergent adverse events (84.9% vs 76.3%)
• Grade 3/4 infections were higher with tecl versus PVd/Kd (41.6% vs 29%)

Clinical Implications

This marks another positive phase 3 study for teclistamab, building on the success of MajesTEC-3 and supporting its potential role for an early-relapse therapy option for patients with multiple myeloma who have received 1 to 3 lines of treatment. However, the requirement for step-up dosing, cytokine release syndrome monitoring, and elevated infection risk will be important considerations for real-world adoption, particularly in the community practice setting. Detailed efficacy, safety, and subgroup analyses will be presented at the ASCO Annual Meeting on May 29, 2026. 

As bispecific antibodies continue to demonstrate improved survival outcomes, including now in earlier lines of therapy, effective strategies for safe outpatient and community-based delivery will be increasingly essential.