Clinical Summary: 

• Design/Population: The phase 3 MajesTEC-9 trial compared teclistamab monotherapy with standard-of-care regimens consisting of carfilzomib-dexamethasone or pomalidomide, bortezomib, and dexamethasone in patients with relapsed/refractory multiple myeloma who had received 1 to 3 prior lines of therapy and were previously exposed to both lenalidomide and anti-CD38 monoclonal antibodies.
• Key Outcomes: Teclistamab significantly improved progression-free survival compared with standard therapy. At 18 months, approximately 80% of patients treated with teclistamab remained alive and progression-free. Complete response rates were substantially higher with teclistamab, and MRD negativity rates were markedly improved. Overall survival was also significantly prolonged with teclistamab.
• Clinical Relevance: These findings support earlier use of BCMA-targeted bispecific antibody therapy and establish teclistamab as a potential new standard of care for patients with relapsed/refractory multiple myeloma after lenalidomide and anti-CD38 exposure.

Roberto Mina, MD, Winship Cancer Institute, Emory University, Atlanta, Georgia, discusses results from the phase 3 MajesTEC-9 trial evaluating teclistamab monotherapy versus standard-of-care treatment in patients with relapsed or refractory multiple myeloma. The study enrolled a heavily pretreated population, the majority of whom were refractory to both lenalidomide and daratumumab, representing a group with historically poor outcomes.

Teclistamab demonstrated significant improvements in progression-free survival, overall survival, depth of response, and MRD negativity compared with standard therapy. The safety profile was consistent with prior teclistamab studies, with mostly low-grade cytokine release syndrome, infrequent ICANS, and manageable infections that declined over time with appropriate supportive care. These results support moving BCMA-directed bispecific antibody therapy into earlier lines of treatment and reinforce teclistamab as a new treatment standard in relapsed/refractory multiple myeloma.

These results were presented by Cyrille Touzeau, MD, PhD, University Hospital Nantes, Nantes, France, at the European Hematological Association (EHA) Annual Meeting in Stockholm, Sweden. 

Transcript: 

My name is Roberto Mina, and I'm an associate professor of hematology at Winship Cancer Institute at Emory University. I would like to discuss with you today the results from the MajesTEC-9 study, which was presented at the EHA meeting in Stockholm in June 2026.

MajesTEC-9 is a phase 3 study that compared teclistamab monotherapy versus standard-of-care treatment consisting of either Kd or PVd in patients with relapsed or refractory multiple myeloma who had received 1 to 3 prior lines of therapy and had been previously exposed to both lenalidomide and an anti-CD38 monoclonal antibody such as daratumumab. The majority of patients enrolled in this study were not only exposed to, but also refractory to, both lenalidomide and daratumumab.

In this context, the study compared an innovative BCMA-targeting treatment, teclistamab, a bispecific antibody, versus standard-of-care therapy. The primary end point of the study was progression-free survival, and the study met its primary end point. Teclistamab was associated with significantly longer progression-free survival than the control arm. The median PFS in the control arm was only 8 months, whereas the median PFS was not reached in patients receiving teclistamab. At 18 months, roughly 80% of patients treated with teclistamab were alive and progression-free, corresponding to a hazard ratio for progression-free survival of 0.29. 

Importantly, the study also demonstrated an overall survival advantage with teclistamab compared with standard-of-care treatment, showing a significant improvement in overall survival and supporting the use of BCMA-targeted therapy earlier in the treatment course of our patients. Responses were more common with teclistamab, both in terms of overall response rate and complete remission rate. Approximately 66% of patients achieved a complete remission with teclistamab compared with only 27% of patients treated with PVd or Kd.

Similarly, responses were not only more frequent but also deeper. MRD negativity was observed more commonly with teclistamab than with standard-of-care treatment. In the intention-to-treat population, MRD negativity rates were 39% with teclistamab compared with only 7% in the control arm. So responses were more common, deeper, and more durable.

In terms of safety, the study showed a safety profile consistent with what we have previously observed with teclistamab monotherapy. Cytokine release syndrome was common but was predominantly grade 1 or 2. ICANS was uncommon, and both events were managed according to standard protocols. Infections were commonly observed in both treatment arms, as was hypogammaglobulinemia. Certain infections were more common with teclistamab, as expected given that this agent targets BCMA. Importantly, however, most serious events occurred during the first 6 months of treatment and then decreased significantly over time.

This highlights the importance of vigilant clinical monitoring, the use of immunoglobulin replacement therapy when appropriate, and adherence to antimicrobial prophylaxis recommendations as outlined in international guidelines to reduce infection risk.

Overall, the results from MajesTEC-9 demonstrated a progression-free survival and overall survival advantage for teclistamab over standard-of-care therapy. Together with the results from MajesTEC-3, which evaluated teclistamab-based combinations versus standard-of-care treatment in patients with one to three prior lines of therapy, these findings support the use of BCMA-targeting bispecific antibody therapy with teclistamab as a backbone treatment for patients with relapsed/refractory multiple myeloma in earlier lines of therapy, potentially as early as the second-line setting. 

These data support a new standard of care for this patient population.

Source: 

Touzeau C, Mina R, Hungria V, et al. MajesTEC-9: A phase 3 study of teclistamab monotherapy vs pomalidomide/bortezomib/dexamethasone or carfilzomib/dexamethasone (PVd/Kd) in patients (pts) with relapsed refractory multiple myeloma (RRMM). Presented at EHA Congress. June 11 - June 14, 2026. Stockholm, Sweden. Abstract EHA-3429.