ASH 2025 | Initial results from MajesTEC-3: Tec-Dara versus DPd/DVd in patients with R/R multiple myeloma

So hello, I’m Luciano Costa, myeloma physician, University of Alabama, Birmingham. At ASH 2025, we had a late-breaking abstract coordinated with a simultaneous publication in the New England Journal of Medicine of the primary results of the MajesTEC-3 trial. So this was a large randomized global trial enrolling patients who had multiple myeloma with one to three prior lines of therapy who had been exposed to a proteasome inhibitor and lenalidomide and turned out the vast majority, over 85%, were lenalidomide-refractory and could or could not have received an anti-CD38 monoclonal antibody so long as the disease was not refractory to it. And those patients, we usually use a CD38-containing regimen in that circumstance. So they’re randomized between daratumumab containing triplets, DPd or DVd, or daratumumab plus teclistamab, or Tec-Dara. 

And this trial is reported now as the first interim analysis. And it shows substantial improvement in the primary endpoint progression-free survival with a hazard ratio of 0.17, and a 36-month progression-free survival for the experimental arm that was over 83%. This trial also shows improvement on the experimental arm for other parameters of efficacy, including complete response, overall response rate, MRD negative complete response. But quite a rare thing, it shows improvement in overall survival already with the first interim analysis with a hazard ratio of 0.46. 

We saw, you know, quite overall comparable toxicity in terms of overall toxicity in grade three and four toxicities. There were a few more serious and fatal infections on the teclistamab-dara than it was on the dara-containing triplets, but that excess in toxicity was mostly during the first six months and preceded the introduction of broader infection mitigating strategies that we all consider standard, like immunoglobulin replacement, growth factor use, PJP prophylaxis, and so forth. 

So we’re all very surprised by the magnitude, by the effect size of the intervention here, the bispecific T-cell engager applied in second to fourth line therapy. And we believe the data is robust enough to represent a new standard of care. We saw this benefit does not seem to be restricted to any patient subset. We’re seeing across all stages, all genetic risk groups. We’re seeing for older patients, with patients with extramedullary disease, and we’re seeing among patients who have received prior daratumumab therapy. We anticipate this study will yield eventual regulatory approval so we can give access to highly effective and safe T-cell redirecting therapy for patients as early as in second line, which is clearly a transformative intervention compared to what the options we’ve had before.

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