Randomized phase 2 trial of teclistamab versus lenalidomide-dexamethasone in high-risk smoldering multiple myeloma

The BCMA-targeting bispecific antibody teclistamab has demonstrated substantial activity in relapsed multiple myeloma, particularly in earlier lines of therapy, and may have higher efficacy in high-risk smoldering multiple myeloma (HR-SMM) with a more functional immune system. The multicenter randomized phase 2 ImmunoPRISM trial compared fixed-duration teclistamab versus lenalidomide-dexamethasone (Rd) in HR-SMM. After a six-patient safety run-in, patients were randomized 2:1 to teclistamab or Rd. The primary endpoint was complete response (CR) rate. As of 26 May 2026, 59 patients were treated – 45 received teclistamab and 14 received Rd. The figure shows efficacy results. Teclistamab treatment induced a CR in 77.8% of patients, versus 0% with Rd, and minimal residual disease negativity at 10^-5 in 82.2%. At a median follow-up of 24.5 months, two-year progression-free survival rate was 92% with teclistamab versus 49% with Rd. Response rates, duration of response, and time to progression were significantly improved with teclistamab compared to Rd. Toxicities in the teclistamab group included grade 1-2 cytokine release syndrome, no neurotoxicity, and no increase in grade 3 infections compared to Rd (20% versus 21%). No deaths occurred in either arm. The authors conclude that teclistamab represents a highly active immune-interception strategy for HR-SMM.