Teclistamab (BCMAxCD3 bispecific) drives 78% CR and 92% 2-year PFS in high-risk smoldering myeloma

Teclistamab is a BCMA-targeting T-cell–redirecting bispecific antibody tested as a fixed-duration “immune interception” strategy in the randomized Phase 2 ImmunoPRISM trial (NCT05469893) versus lenalidomide–dexamethasone (Rd) in high-risk smoldering multiple myeloma (HR-SMM); 59 treated patients were analyzed (teclistamab n=45; Rd n=14). Teclistamab achieved a 77.8% complete response rate vs 0% with Rd and MRD negativity (10^-5) in 82.2%; at median follow-up of 24.5 months, 2-year PFS was 92% vs 49%. The treatment landscape has shifted since this trial began: in the US, high-risk SMM can now be managed with active monitoring or daratumumab for up to 36 months, making the contemporary question whether deeper BCMA-directed responses translate into enough long-term benefit to justify greater immune suppression. Safety with teclistamab included grade 1–2 CRS, no neurotoxicity, and grade ≥3 infections in 20% vs 21% with Rd, with no deaths in either arm.