Teclistamab Extends Survival Vs SOC in Refractory Multiple Myeloma Trial

Teclistamab-cqyv (Tecvayli) monotherapy outperformed standard-of-care (SOC) regimens in terms of progression-free survival (PFS) and overall survival (OS) among patients with multiple myeloma predominantly refractory to CD38-directed therapy and lenalidomide (Revlimid), according to a news release on topline data from the phase 3 MajesTEC-9 trial (NCT05572515).¹

Administering teclistamab alone reduced the risk of progression or death by 71% vs standard therapy (HR, 0.29; 95% CI, 0.23-0.38). Regarding OS, the risk of death decreased by 40% among those assigned to receive teclistamab (HR, 0.60; 95% CI, 0.43-0.83).

The safety profile of teclistamab in the MajesTEC-9 study was comparable with prior reports of the agent; toxicities were manageable with established protocols, and investigators observed no new safety signals.

An independent data monitoring committee recommended unblinding the study based on the data observed in the first prespecified interim analysis. Investigators plan to present detailed results from MajesTEC-9 at a future medical conference and share them with regulatory health authorities across the world.

According to the news release, findings from the MajesTEC-9 study build upon results from the phase 3 MajesTEC-3 trial (NCT05083169), in which teclistamab plus daratumumab and hyaluronidase-fihj (Darzalex Faspro) decreased the risk of progression or death by 83% compared with standard regimens among those with relapsed/refractory multiple myeloma (HR, 0.17; 95% CI, 0.12-0.23; P <.0001).²

“The MajesTEC-9 results reinforce the potential of [teclistamab] to transform treatment earlier in the multiple myeloma journey, with an immunotherapy regimen widely available for all appropriate patients, including those commonly treated in the community setting,” Roberto Mina, MD, associate professor at Winship Cancer Institute of Emory University and former assistant professor at University of Turin in Turin, Italy, stated in the news release.¹ “The impressive results show a significant improvement in [PFS] and [OS] as a monotherapy in patients with refractory multiple myeloma, and together with the MajesTEC-3 results, help establish [teclistamab] as an essential therapy for patients as early as first relapse.”

Investigators of the MajesTEC-9 study assessed the safety and efficacy of teclistamab vs SOC therapy with pomalidomide (Pomalyst) plus bortezomib (Velcade) and dexamethasone (PVd) or carfilzomib (Kyprolis) plus dexamethasone among patients with 1 to 3 prior lines of treatment for relapsed/refractory multiple myeloma. All patients had prior treatment with an anti-CD38 monoclonal antibody plus lenalidomide, and most were refractory to prior CD38-directed monoclonal antibodies (85%) and lenalidomide (79%).

The trial’s primary end points included PFS in part 1, and cytokine release syndrome in part 2.³ Secondary end points included overall response rate, complete response rate, duration of response, time to next treatment, OS, and adverse effects.

Patients 18 years and older with documented multiple myeloma per International Myeloma Working Group guidelines, 1 to 3 prior lines of treatment, including at least 2 cycles of anti-CD38 monoclonal antibodies and 2 consecutive cycles of lenalidomide, and documented progression on the most recent line of treatment were eligible for enrollment on the trial. Other eligibility criteria included having an ECOG performance status of 0 to 2 and willingness to adhere to lifestyle restrictions specified in the study protocol.

Those with prior receipt of anti–B-cell maturation antigen therapy, a maximum cumulative dose of corticosteroids at 140 mg or higher of prednisone or an equivalent dose within 2 weeks before randomization, or central nervous system involvement or signs or meningeal involvement of multiple myeloma were ineligible for enrollment on the trial. Having plasma cell leukemia, Waldenström macroglobulinemia, polyneuropathy, organomegaly, endocrinopathy, M-protein syndrome, and skin changes, or primary amyloid light chain amyloidosis, was also grounds for exclusion from the trial.

References

1. TECVAYLI monotherapy demonstrates superior progression-free and overall survival versus standard of care as early as first relapse in patients with multiple myeloma predominantly refractory to anti-CD38 therapy and lenalidomide. News release. Johnson & Johnson. January 14, 2026. Accessed January 15, 2026. https://tinyurl.com/ycxxw2np
2. Unprecedented results from the phase 3 MajesTEC-3 study support TECVAYLI plus DARZALEX FASPRO as a potential standard of care as early as second line for patients with relapsed/refractory multiple myeloma. News release. Johnson & Johnson. December 9, 2025. Accessed January 15, 2026. https://tinyurl.com/5h3e67jb
3. A study comparing teclistamab monotherapy versus pomalidomide, bortezomib, dexamethasone (PVd) or carfilzomib, dexamethasone (Kd) in participants with relapsed or refractory multiple myeloma (MajesTEC-9). ClinicalTrials.gov. Updated December 19, 2025. Accessed January 15, 2026. https://tinyurl.com/42yxtpz2