Exploring New Data: Teclistamab and Daratumumab in Multiple Myeloma

MajesTEC-3 demonstrated a striking improvement in progression-free survival for relapsed or refractory multiple myeloma with an investigational teclistamab-daratumumab combination.

The phase 3 trial randomized 587 patients with one to three prior lines of therapy to the experimental combination versus investigator-selected standard regimens, with progression-free survival prespecified as the primary endpoint. The investigators reported a 36-month PFS of 83.4% for the investigational arm versus 29.7% for standard options at a median follow-up of 34.5 months.

The combination produced markedly higher durable remissions and objective response rates, with deeper and more sustained responses in key subgroups including patients refractory to prior lenalidomide; patients with one prior line had large absolute gains in disease control. The immunologic pairing of teclistamab and daratumumab was reported to deliver extended durations of response, and the trial provided one of the longest 3-year PFS estimates reported for a second-line study in recent years.

Serious adverse events were common but did not eliminate the efficacy signal. 70.7% of patients on the investigational arm versus 62.4% on standard regimens experienced serious AEs. Immune-mediated toxicities including cytokine release syndrome (CRS) and treatment-related neurologic events occurred, and infection rates were higher with the bispecific-containing regimen.

Key Takeaways:

• MajesTEC-3 showed a large PFS benefit at 36 months for the teclistamab–daratumumab combination versus standard regimens, supporting its consideration in relapsed/refractory patients.
• The benefit was most pronounced in patients with one prior line and those with lenalidomide-refractory disease, indicating prioritized use early in relapse.