Teclistamab Plus Daratumumab Significantly Prolongs Survival in Relapsed or Refractory Multiple Myeloma

By: Wendy LaGrego
Posted: Wednesday, March 4, 2026

The treatment of relapsed or refractory multiple myeloma continues to evolve amid increasing front-line complexity and progressive immune dysfunction. Although daratumumab-based regimens and B-cell maturation antigen (BCMA)–directed therapies have reshaped the therapeutic landscape, optimal strategies for patients in the first to third relapse remain under active investigation. In the recent MajesTEC-3 study, Costa et al. evaluated the combination of the BCMA×CD3 bispecific antibody teclistamab with daratumumab in patients with relapsed or refractory multiple myeloma who had received one to three prior lines of therapy. Their results were published in The New England Journal of Medicine.

Study Details

MajesTEC-3 was an international, open-label, randomized phase III trial conducted across 150 sites in 20 countries between October 2021 and September 2023. Eligible participants had received one to three prior lines of antimyeloma therapy, including both a proteasome inhibitor and lenalidomide, and had documented disease progression. Patients were randomly assigned in a 1:1 ratio to receive teclistamab plus daratumumab or investigator’s choice of daratumumab combined with pomalidomide and dexamethasone (DPd) or bortezomib and dexamethasone (DVd). The primary endpoint was progression-free survival  assessed by independent review.

A total of 587 patients underwent randomization, with 291 patients assigned to teclistamab plus daratumumab and 296 to DPd or DVd. Baseline characteristics were balanced between groups, and the median follow-up was 34.5 months.

Key Results

At the first interim analysis, teclistamab plus daratumumab significantly reduced the risk of disease progression or death, meeting the prespecified superiority boundary. The estimated 36-month progression-free survival was 83.4% in the teclistamab plus daratumumab group compared with 29.7% in the DPd or DVd group (hazard ratio = 0.17; 95% confidence interval = 0.12–0.23; P < .001).

Depth of response also favored the investigational combination. A complete response or better was achieved in 81.8% of patients receiving teclistamab plus daratumumab compared with 32.1% in the control group, and minimal residual disease negativity at a sensitivity of 10^-5 was observed in 58.4% vs 17.1%, respectively (P < .001 for all comparisons). Overall survival was similarly improved: 36-month overall survival was 83.3% with teclistamab plus daratumumab vs 65.0% with DPd or DVd (P < .0001). As the authors noted, treatment with teclistamab plus daratumumab was associated with “an 83% reduction in the risk of disease progression or death.”

Safety findings were consistent with the known profiles of the individual agents. Grade 3 or 4 neutropenia occurred in 75.6% of patients receiving teclistamab plus daratumumab and 78.6% of those receiving DPd or DVd. Cytokine release syndrome was reported in 60.1% of patients in the teclistamab plus daratumumab arm, all grade 1 or 2, with no events leading to treatment discontinuation. Infections were more frequent with the combination, particularly early in therapy.

According to the study authors, the MajesTEC-3 trial demonstrated that teclistamab plus daratumumab significantly prolongs progression-free and overall survival and induces deep, durable responses in patients with relapsed or refractory multiple myeloma.

“In patients with multiple myeloma who had received one to three previous lines of therapy, those in the teclistamab–daratumumab group had significantly longer progression-free survival than those in the DPd or DVd group,” they concluded.

DISCLOSURE: For full disclosures of all study authors, visit nejm.org.

The New England Journal of Medicine

---