Phase 2 daratumumab plus teclistamab is compared with DPd or DKd in high-risk, second-line multiple myeloma

This randomized NCI Phase 2 study compares daratumumab-hyaluronidase plus teclistamab with daratumumab/pomalidomide/dexamethasone (DPd) or daratumumab/carfilzomib/dexamethasone (DKd) in high-risk multiple myeloma after one prior treatment line. Daratumumab targets CD38, while teclistamab engages BCMA on myeloma cells and CD3 on T cells. The main efficacy question is whether the combination increases measurable residual disease negativity after 6 cycles in this specifically high-risk population.

Participants must be anti-CD38-treatment naive or sensitive; previously exposed patients must be more than 180 days from their last daratumumab or isatuximab dose at randomization. Importantly, teclistamab plus daratumumab received FDA approval on March 5, 2026, for adults after at least one prior line including a proteasome inhibitor and an immunomodulatory agent. The trial now provides a focused randomized assessment of a recently approved combination in a specifically high-risk, second-line population. Infection, cytopenia, cytokine-release syndrome, and neurologic-toxicity monitoring remain important.