MajesTEC results for teclistamab plus daratumumab in MM

In a phase 3 study, a novel treatment regimen for patients with relapsed or refractory multiple myeloma (MM) outperformed the current standard of care, demonstrating improved survival outcomes. The efficacy data even suggested that this new therapy may be capable of delivering a functional cure.

The MajesTEC-3 study (NCT05083169) randomised 587 participants with relapsed or refractory MM in a 1:1 ratio to receive the experimental combination of teclistamab and daratumumab or the investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd). “Included participants had received 1 to 3 prior lines of therapy,” said Prof. María-Victoria Mateos (University of Salamanca, Spain) [1].

After a median follow-up of 34.5 months, the experimental therapy met the primary endpoint of progression-free survival (PFS). The 3-year PFS rates were 83.4% in the teclistamab plus daratumumab arm and 29.7% in the DPd/DVd arm, respectively (HR 0.17; 95% CI 0.12–0.23; P<0.0001). The overall survival data also favoured the experimental arm, with 3-year overall survival rates of 83.3% versus 65.0%, respectively (HR 0.46; 95% CI 0.32–0.65; P<0.0001).

Prof. Mateos highlighted key safety findings. “Cytokine release syndrome was observed in 60.1% of the participants in the experimental arm,” she noted. “All events were grade 1 or 2.” Immune effector cell-associated neurotoxicity syndrome (ICANS) occurred in 1.1% of the participants receiving teclistamab; all events resolved. Grade 3 or 4 infections were reported in 54.1% of participants in the experimental arm and 43.4% in the control arm. Thirteen participants in the teclistamab arm died from infections. “Twelve of these cases occurred within the first 6 months of therapy, and 9 participants had not received immunoglobulin replacement therapy,” Prof. Mateos explained. “These findings highlight the need for diligent use of immunoglobulin replacement and infection prophylaxis in patients treated with teclistamab plus daratumumab.”

“The combination of teclistamab and daratumumab demonstrated unprecedented efficacy, supporting a new standard of care in the second-line and later settings for patients with MM,” concluded Prof. Mateos. “The plateauing of the PFS curve after approximately 6 months suggests the potential for a functional cure with this therapy.”

1. Mateos M-V, et al. Phase 3 randomized study of teclistamab plus daratumumab versus investigator’s choice of daratumumab and dexamethasone with either pomalidomide or bortezomib (DPd/DVd) in patients with relapsed or refractory multiple myeloma (RRMM): results of MajesTEC-3. LBA-6, American Society of Hematology (ASH) annual meeting 2025, 6–9 December, Orlando, Florida, USA.

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Posted on 22 December 202522 December 2025