New Reference: Teclistamab for Relapsed / Refractory Multiple Myeloma

In this phase 3 trial, teclistamab monotherapy significantly improved progression-free and overall survival compared with pomalidomide-based or carfilzomib-based regimens in patients with relapsed or refractory multiple myeloma previously treated with anti-CD38 antibodies and lenalidomide. Despite more grade 3-4 adverse events and infections, teclistamab produced deeper and more durable responses, with a glucocorticoid-sparing regimen and delayed symptom worsening.

Study

Phase 3, open-label, multicenter, randomized trial [MajesTEC-9]

Rel/ref multiple myeloma, with 1-3 prior lines including anti-CD38 monoclonal antibody and lenalidomide

Teclistamab monotherapy (n=296) vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone (PVd) or carfilzomib and dexamethasone (Kd) (n=297)

Efficacy

ORR: 84.5% vs 54.2% (teclistamab vs. investigators’ choice) (RR 1.56 [1.39-1.75])

CR or better: 65.9% vs 16.8% (RR 3.95 [3.03-5.14])

18-mo PFS: 69.8% vs 26.9% (HR 0.29 [0.23-0.38])

18-mo OS: 79.2% vs 68.6% (HR 0.60 [0.43-0.83])

Time to symptom worsening: HR 0.50 [0.36-0.71] favoring teclistamab

mDoR: Not reached vs 13.4 mos

Safety

Grade >=3 AE: neutropenia (54.3% vs 22.3%), anemia (17.9% vs 16.3%), thrombocytopenia (10.7% vs 21.2%), lymphopenia (20.3% vs 11.3%), cytokine release syndrome (0.7% vs 0%), pneumonia (14.4% vs 10.6%), hypertension (4.5% vs 11.3%)

Grade 5 AEs: 6.5% vs 3.5%

CRS (any grade) in teclistamab: 66.0%, mostly grade 1 or 2

ICANS with teclistamab: 4.1%, mostly grade 1 or 2

Treatment discontinuation due to AE: 10.7% vs 13.1%