As reported at the 2026 ASCO Annual Meeting and in The New England Journal of Medicine by Touzeau et al, an interim analysis of the phase III MajesTEC-9 trial has shown improved progression-free survival with teclistamab vs investigator's choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) in previously treated patients with relapsed or refractory multiple myeloma.
Study Details
In the international open-label trial, 593 patients with one to three prior lines of therapy, including an anti-CD38 monoclonal antibody and lenalidomide, were randomly assigned between April 2023 and April 2025 to receive teclistamab (n = 296) or investigator's choice of PVd or Kd (n = 297). Teclistamab was given subcutaneously in 28-day cycles in two step-up doses (0.06 and 0.3 mg/kg), followed by weekly doses of 1.5 mg/kg in cycles 1 and 2, 3 mg/kg every 2 weeks in cycles 3 through 6, and 3 mg/kg every 4 weeks from cycle 7 onward. Patients received PVd or Kd according to approved administration schedules in 21-day cycles for PVd or 28-day cycles for Kd. Antimicrobial prophylaxis and immune globulin replacement were recommended. The primary endpoint was progression-free survival on independent review committee assessment.
Key Findings
At interim analysis (median follow-up = 17.3 months), 18-month progression-free survival was 69.8% in the teclistamab group vs 26.9% in the PVd/Kd group (hazard ratio [HR] = 0.29, 95% confidence interval [CI] = 0.23–0.38, P < .001).
Complete response or better was observed in 65.9% of the teclistamab group vs 16.8% of the PVd/Kd group (P < .001). Overall survival at 18 months was 79.2% vs 68.6% (HR = 0.60, 95% CI = 0.43–0.83, P = .002).
Adverse events of grade 3 or 4 occurred in 84.9% of the teclistamab group and 76.3% of the PVd/Kd group, most commonly neutropenia (54.3% vs 22.3%); grade 5 adverse events occurred in 6.5% and 3.5%. Cytokine-release syndrome occurred in 66.0% of the teclistamab group (grade 1 or 2 in all but two patients), and immune effector cell–associated neurotoxicity syndrome occurred in 4.1%. Grade 3 or 4 infection occurred in 41.6% vs 29.0% of patients. Death considered related to treatment occurred in 12 patients (4.1%) in the teclistamab group and 5 patients (1.8%) in the PVd/Kd group.
The investigators concluded: “Among patients with multiple myeloma and one to three previous lines of therapy, teclistamab significantly improved progression-free and overall survival as compared with PVd or Kd. Infections of grade 3 or 4 were common.”
Cyrille Touzeau, MD, PhD, of Service d’Hematologie Clinique, Centre Hospitalier Universitaire, Nantes, France, is the corresponding author for the New England Journal of Medicine article.
DISCLOSURE: The study was funded by Johnson & Johnson. For full disclosures of the study authors, visit nejm.org.
