Talquetamab-Based Combinations Significantly Improve Outcomes in Early Relapsed Multiple Myeloma
Clinical Summary:
- Design/Population: The phase 3 MonumenTAL-6 trial randomized 795 patients with multiple myeloma who had received 1 to 4 prior lines of treatment to receive either talquetamab plus teclistamab, talquetamab plus pomalidomide, or investigator’s choice of elotuzumab plus pomalidomide and dexamethasone or pomalidomide, bortezomib, and dexamethasone.
- Key Outcomes: Talquetamab plus teclistamab significantly improved progression-free and overall survival compared with investigator’s choice, while talquetamab plus pomalidomide also significantly improved progression-free survival. The findings demonstrate substantial efficacy with talquetamab-based combinations in the early relapse setting.
- Clinical Relevance: These topline findings support moving bispecific antibody-based regimens into earlier lines of multiple myeloma treatment may reshape therapeutic strategies for patients experiencing early relapse.
Ajay Nooka, MD, MPH, Emory University Winship Cancer Institute, Atlanta, Georgia, discusses topline results from the phase 3 MonumenTAL-6 trial evaluating talquetamab-based combinations in patients with multiple myeloma who had received 1 to 4 prior lines of therapy.
Dr Nooka reviews the significant progression-free survival benefit observed with talquetamab plus teclistamab and talquetamab plus pomalidomide compared with standard treatment, as well as the overall survival benefit reported with dual GPRC5D- and BCMA-directed bispecific antibody therapy. He also discusses how these findings build upon earlier experience with talquetamab and support moving bispecific antibody combinations into earlier lines of multiple myeloma treatment, with the potential to achieve deeper and more durable disease control.
Transcript:
My name is Ajay Nooka, I'm the director of the myeloma program at the Emory Winship Cancer Institute.
I'm here to discuss the topline results for MonumenTAL-6 trial, which is a trial that was done in the early relapsed multiple myeloma space for patients who had seen 1 to 4 prior lines of therapy. This trial has shown a hazard ratio of 0.11, which is an 89% reduction in the risk of progression of death.
In the myeloma landscape, the bispecific antibodies have changed how we treat multiple myeloma, mostly in the relapsed or refractory space. The MonumenTAL-1 trial evaluated talquetamab as a single agent in 2 dosing schedules at 0.4 mg/week and at 0.8 mg/every other week/kg. What has resulted in terms of the efficacy results were a 74% overall response rate and this has led to the approval of talquetamab in the late relapse setting.
When you start to look at the response rates in this area, say for example, daratumab, a CD38 antibody as a single agent that we use in this space, yielded a response rate of around 30%. Selinexor, that was approved in the same space, yielded a response rate of 30%, and belantamab, as a single agent, had a response rate of 30%. All of these are active drugs and in that space, seeing response rates of close to more than 70% or so is just unprecedented.
MonumenTAL-1 is a single-arm trial that led to the approval of talquetamab. When you talk about these approvals, this is a conditional approval, which means these studies need to be proven with a confirmatory study, and that's where the confirmatory study was, in the early relapse space.
The MonumenTAL-6 trial had 3 arms and 795 patients were randomized to talquetamab, which is a GPR-C50 bispecific antibody, plus teclistamab, which is a BCMA bispecific antibody. The second arm is talquetamab plus pomalidomide, an immunomodulatory agent. The third arm is investigator's choice, which is elotuzumab plus pomalidomide and dexamethasone or pomalidomide plus bortezomib and dexamethasone. For these 3 arms, it's a 1:1:1 randomization, and the primary end point is progression-free survival.
We have not seen the results, but the topline results, the ones that were announced showed compared to teclistamab and talquetamab, they're both bispecific antibodies targeting GPRC5D and BCMA, had a hazard ratio of 0.11 compared to the investigator's choice of elotuzumab plus pomalidomide and dexamethasone or pomalidomide plus bortezomib and dexamethasone. This means there's an 89% reduction in the risk of progression or death.
This is where it boils down to the efficacy of these bispecific antibody combinations much earlier in the space of multiple myeloma, and these are resulting in such good responses and durable remissions for a longer period. Not only showed the PFS benefit, it also showed an overall survival benefit. Compared to the standard-of-care arm, this combination of teclistamab and talquetamab had an overall survival hazard ratio of 0.38. That's a 62% reduction in the risk of progression.
Now, what did the other arm do? The talquetamab plus pomalidomide had a hazard ratio of 0.27 for PFS, which is again significant. It is a 73% reduction in the risk of progression, all talking about how good these bispecific antibodies are either by themselves or in combinations in the early relapse setting.
In myeloma, these studies are going to change how we treat the early relapse myeloma in the future. The bispecific antibodies are here, they're going nowhere, and that benefit is proven not only in the relapsed or refractory space, but also in the early relapse space and in the future maybe in the front-line setting as well.
These studies show how good these agents are in terms of not only the efficacy, but also the safety and these will be more used in the future to get the good long-term remissions for our myeloma patients.
Source:
PR Newswire. TECVAYLI® + TALVEY® reduced the risk of disease progression or death by 89% and the risk of death by 62% in earlier-line relapsed/refractory multiple myeloma. Accessed on July 23, 2026. https://www.prnewswire.com/news-releases/tecvayli--talvey-reduced-the-risk-of-disease-progression-or-death-by-89-and-the-risk-of-death-by-62-in-earlier-line-relapsedrefractory-multiple-myeloma-302833309.html
