Clinical Summary:

• Design/Population: MajesTEC-9 was a phase 3 randomized trial comparing teclistamab monotherapy with physician’s choice of standard-of-care therapy in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy and were previously exposed to lenalidomide and an anti-CD38 antibody.
• Key Outcomes: Teclistamab significantly improved progression-free survival, reducing the risk of disease progression or death by 71% versus standard of care. The treatment also increased overall response and complete response rates.
• Clinical Relevance: The MajesTEC-9 results establish early use of BCMA-targeted therapy as a highly effective treatment strategy in relapsed multiple myeloma. Together with findings from MajesTEC-3, these data support teclistamab as a new standard-of-care option beginning in the second-line setting.

Roberto Mina, MD, Winship Cancer Institute of Emory University, Atlanta, Georgia, discusses results from the phase 3 MajesTEC-9 trial comparing teclistamab monotherapy and physician’s choice standard-of-care in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy and prior exposure to lenalidomide and an anti-CD38 antibody.

Results showed that teclistamab significantly improved progression-free survival (PFS), reducing the risk of disease progression or death by 71% compared with standard of care, while also increasing complete response and minimal residual disease (MRD)-negative rates. Teclistamab additionally demonstrated an overall survival (OS) benefit, reducing the risk of death by 40%, despite substantial use of subsequent bispecific antibody and CAR T-cell therapies in the control arm. These findings, together with results from the MajesTEC-3 study, support BCMA-targeted therapy as a new standard of care for patients with relapsed multiple myeloma beginning as early as the second-line setting.

Dr Mina presented these results at the 2026 ASCO Annual Meeting in Chicago, Illinois.

Transcript:

My name is Roberto Mina and I am an associate professor of hematology at the Winship Cancer Institute, Emory University. 

We presented data from the MajesTEC-9 study, a phase 3 trial that randomized patients between teclistamab monotherapy—a BCMA bispecific antibody already approved for the treatment of patients with relapsed and refractory multiple myeloma—and physician’s choice of standard-of-care therapy.

In the MajesTEC-9 study, teclistamab monotherapy was compared with physician’s choice of standard-of-care treatment for patients who had received 1 to 3 prior lines of therapy. Patients had to have been exposed to both lenalidomide and an anti-CD38 antibody. The physician’s choice standard-of-care treatment consisted of either KD (carfilzomib and dexamethasone) or PVd (pomalidomide, bortezomib, and dexamethasone).

In the experimental arm, patients instead got teclistamab monotherapy, which is a steroid-free regimen. Patients did not receive any steroid after the step-up dosing and the first full dose. In addition, monthly dosing was implemented from Cycle 7 onward, or earlier for patients who achieved a very good partial response (VGPR).

This is an important study because we are treating with a BCMA-targeted bispecific antibody patients in earlier lines of treatment– we know [that] despite the advantages of the use of triplets and quadruplets upfront, patients with myeloma still relapse so, we need drugs with a different mechanism of action, drugs with different targets that can further improve their survival.

The key important points from MajesTEC-9 are that teclistamab prolonged progression-free survival significantly compared with the standard-of-care arm, reducing the risk of death or progression by 71%, with a hazard ratio of 0.29, which is one of the best ratios we’ve seen in this setting. Therefore, the study met its primary end point.

Teclistamab improved chances of a patient achieving a response, but more importantly, the chances of a patient achieving remission was significantly higher with a patient receiving teclistamab compared with a standard-of-care treatment. Many patients who achieved a complete remission were also minimal residual disease (MRD)-negative at a sensitivity threshold of 10^-5.

Even more importantly, this study also met another key secondary end point, teclistamab prolonged the overall survival at an early time point versus standard-of-care treatment, and we have a reduction of the risk of death as compared with the standard-of-care arm by 40%. This is a very important point, because 2/3 of patients in the control arm received a bispecific antibody or CAR T in a subsequent line of therapy. So, despite the exposure to highly effective treatment, the use of early teclistamab led to an improved not only in progression-free survival but also overall survival.

In the context of 2 large phase 3 studies, MajesTEC-9 and MajesTEC-3, that both showed improved PFS but also overall survival, we now know that BCMA-targeted therapy is the a standard of care for patients with relapsed myeloma as early as the second line of treatment. Teclistamab is a new standard of care in this setting, either as monotherapy based on the MajesTEC-9 results, or in combination with daratumumab based on MajesTEC-3.

Source:

Mina R, Touzeau C, Hungria V, Landgren CO, Bhutani D, et al. MajesTEC-9: A phase 3 randomized study of teclistamab monotherapy vs investigator’s choice of pomalidomide, bortezomib, and dexamethasone or carfilzomib and dexamethasone (PVd/Kd) in patients with relapsed refractory multiple myeloma (RRMM). Presented at the ASCO Annual Meeting. May 29–June 2, 2026. Chicago, Illinois. Abstract 7507.