Teclistamab plus Daratumumab in Relapsed or Refractory Multiple Myeloma
- Study type
- Clinical trial
- Study name
- MajesTEC-3
- Phase
- Phase 3
- Design
- Randomised, multicentre, open-label trial
- Sample size
- 587 patients
- Source
- N Engl J Med · 2026
- Trial registration
- NCT05083169
In plain words
In patients with multiple myeloma whose disease had come back after 1 to 3 lines of treatment, combining teclistamab (a drug that links immune cells to myeloma cells) with daratumumab kept the disease under control for up to 3 years in more than 8 out of every 10 patients, compared with about 3 out of 10 with commonly used treatments. Serious side effects, especially infections, were a little more common.
Key results
Treatment arms and regimens
Subcutaneous daratumumab 1800 mg on day 0, then weekly in weeks 2 to 8, every 2 weeks in weeks 9 to 24 and every 4 weeks from week 25. Teclistamab subcutaneously: step-up dose of 0.06 mg/kg on day 1 (at least 20 hours after daratumumab), 0.3 mg/kg on day 3 and a first treatment dose of 1.5 mg/kg on day 7; then 1.5 mg/kg weekly in weeks 2 to 8, 3 mg/kg every 2 weeks in weeks 9 to 24 and 3 mg/kg every 4 weeks from week 25, until disease progression or unacceptable toxicity.
Subcutaneous daratumumab + dexamethasone (oral or IV) plus oral pomalidomide (DPd) or subcutaneous bortezomib (DVd) at the investigator's choice. Doses in the full text of the paper.
Source of the regimen details: FDA label for TECVAYLI (Dosage and Administration section for the combination with daratumumab, and MajesTEC-3); ClinicalTrials.gov NCT05083169 (route of administration); DPd/DVd doses in the full text of the paper
Doses are given for the information of specialists, as in this study’s protocol, and are not a prescription. Every drug must be prescribed by the treating physician for the individual patient.
Study population
Patients with relapsed or refractory multiple myeloma with 1 to 3 prior lines of therapy.
Endpoints
Primary endpoint: progression-free survival assessed by an independent review committee. Secondary endpoints included complete response or better, overall response, minimal residual disease (MRD) negativity and overall survival.
Safety and side effects
Serious adverse events occurred in 70.7% of patients in the teclistamab-daratumumab group and 62.4% of the DPd or DVd group; deaths due to adverse events were 7.1% and 5.9%, respectively.
Clinical significance and place in guidelines
On 5 March 2026 the FDA approved teclistamab with subcutaneous daratumumab for relapsed or refractory myeloma after at least one prior line of therapy including a proteasome inhibitor and an immunomodulatory drug. This was the first phase 3 trial to show marked superiority of a bispecific antibody-based combination in early relapse of myeloma.
Limitations
Open-label design; comparison with DPd/DVd rather than with CAR-T or other new combinations; more serious adverse events and deaths due to adverse events; infections are a major challenge.
This summary was prepared by the editorial team from the published paper; the original paper is the final reference. Read the original abstract on PubMed.