Dual Bispecific Therapy Shows Promise in High-Risk Multiple Myeloma With EMD

Patients with relapsed/refractory multiple myeloma (RRMM) and extramedullary disease (EMD) represent a particularly high-risk population with historically poor outcomes. In a new phase 2 analysis presented at the European Hematology Association (EHA) Congress 2025, results from the REDIRECTT-1 study (NCT04586426) suggest that the combination of 2 bispecific antibodies—talquetamab (Talvey) and teclistamab (Tecvaylo)—may offer meaningful clinical benefit to these patients.

In an interview with Targeted Oncology, Shahzad Raza, MD, hematologist/oncologist at the Cleveland Clinic, explains the rationale behind the study.

"There is a segment within multiple myeloma called extramedullary disease, meaning the disease is present outside the bone marrow, involving the viscera. These patients have a very bad prognosis." He cites real-world data showing that patients with EMD who have been exposed to and relapsed on triple-class therapies (proteasome inhibitors, immunomodulatory drugs, and anti-CD38 monoclonal antibodies) have an objective response rate (ORR) of only 24% and a median overall survival of 7.2 months.

Single-agent bispecific therapies have already demonstrated improved response rates in this setting. In the MonumenTAL-1 trial, talquetamab achieved an ORR of 43.5% in RRMM patients with EMD. Similarly, the MajesTEC-1 trial of teclistamab showed an ORR of 43.4%. However, progression-free survival (PFS) remained a challenge with monotherapy approaches.

In the REDIRECTT-1 phase 1 study that combined talquetamab and teclistamab, investigators reported promising early activity. Among 18 patients with extramedullary plasmacytomas, the 12-month PFS rate was 52.9%. These encouraging results laid the foundation for the phase 2 REDIRECTT-1 trial, specifically designed to evaluate the efficacy of the dual bispecific combination in EMD patients.

"This is the biggest challenge we face," Raza explains. “And that’s why we thought it’s very important to know whether EMDs do better when these two bispecifics are combined together.”

The REDIRECTT-1 trial continues to enroll and analyze outcomes in this high-risk subgroup. If confirmed in larger studies, the talquetamab/teclistamab combination could become a new treatment avenue for patients with relapsed/refractory EMD—a population with very limited options and urgent unmet need.

REFERENCES:

Kumar S, Mateos MV, Ye JC, et al. Phase 2 study of talquetamab + teclistamab in patients with relapsed/refractory multiple myeloma and extramedullary disease: REDIRECTT-1. Presented at: European Hematology Association Congress; June 12-15, 2025; Milan, Italy. LBA4001