Phase 3 linvoseltamab BCMA×CD3 bispecific antibody versus daratumumab anti-CD38 in high-risk SMM.

This Phase 3, randomized, open-label study (LINKER-SMM2) tests whether Regeneron’s linvoseltamab-gcpt—an off-the-shelf T-cell–engaging bispecific monoclonal antibody that binds BCMA on plasma cells and CD3 on T cells—can delay progression from high-risk smoldering multiple myeloma (SMM) to symptomatic multiple myeloma better than daratumumab, a CD38-targeting monoclonal antibody from Janssen (Johnson & Johnson). Participants have high-risk SMM (a precursor state with meaningful near-term progression risk), and are treated in the first-line/pre-myeloma setting rather than after end-organ damage occurs. The key commercial/scientific angle is moving a potent BCMA T-cell engager earlier in the disease course, where deeper immune-mediated clearance and MRD negativity could translate into longer “time-to-myeloma,” but safety/tolerability (e.g., cytokine release syndrome and neurotoxicity risks typical of CD3-engagers) becomes especially important in an otherwise asymptomatic population. Today’s care for most SMM has been close observation; however, daratumumab (including the subcutaneous daratumumab + hyaluronidase formulation) has recently become an active early-treatment option for high-risk SMM, making it a relevant comparator rather than watchful waiting.