Johnson & Johnson: Model suggests Tec‑Dara may normalize long‑term mortality in early‑line RRMM

Study and methods

The Phase 3 MajesTEC‑3 trial compared teclistamab plus subcutaneous daratumumab (Tec‑Dara) with investigator’s choice daratumumab SC plus DPd/DVd in patients with relapsed/refractory multiple myeloma who had received 1–3 prior lines of therapy. A relative survival mixture cure model (MCM) was applied to actual PFS and OS data (Tec‑Dara n=291; DPd/DVd n=296) to assess whether long‑term disease control could approach outcomes of an age‑matched general population.

Modelled long‑term survival

Best‑fit MCM results estimated a cure fraction of 86.6% (95% CI 81–91) for overall survival with Tec‑Dara versus 0% (95% CI 0–53) for DPd/DVd, acknowledging greater uncertainty in the DPd/DVd estimates. Projected remaining life expectancy was 18.5 years with Tec‑Dara, compared with 4.9 years for DPd/DVd and 21.1 years for the matched general population.

Clinical outcomes driving benefit

At 36 months the cumulative incidence of disease progression was 8.7% with Tec‑Dara versus 62.1% with DPd/DVd (subdistribution HR=0.10; 95% CI 0.07–0.16; P<0.0001). The 36‑month OS rate was 83.3% versus 65.0% (HR=0.46; 95% CI 0.32–0.65; P<0.0001). There was no significant difference in non‑relapse mortality (36‑month rates 10.2% vs 9.0%; sHR=1.16; P=0.5668).

Interpretation and next steps

The analyses attribute the projected survival gains to a marked reduction in disease progression rather than increased non‑relapse deaths. MajesTEC‑3 is ongoing; continued follow‑up will determine whether observed outcomes confirm the model‑based projections. The trial’s primary endpoint is PFS, with OS and MRD among key secondary endpoints.