Teclistamab Outperforms Len/Dex in High-Risk Smoldering Myeloma With Higher CR Rate, PFS: Omar Nadeem, MD

Teclistamab (Tecvayli; Janssen Biotech, Inc) demonstrated superior complete response (CR) rates and improved progression-free survival (PFS) compared with lenalidomide and dexamethasone (Len/Dex) in high-risk smoldering multiple myeloma, according to data from the phase 2 ImmunoPRISM trial (NCT05469893) presented today during the late-breaking abstracts session at the European Hematology Association 2026 Congress in Stockholm, Sweden.

Before the meeting, lead investigator Omar Nadeem, MD, spoke with The American Journal of Managed Care^® about the motivation, objectives, and results of the study. He explained that the trial evaluated the BCMA bispecific antibody teclistamab against Len/Dex in patients with high-risk smoldering myeloma, a precursor plasma cell disorder with a 50% risk of progression to overt multiple myeloma within 2 years.

In November 2025, daratumumab and hyaluronidase-fihj (Darzalex Faspro; Janssen Biotech Inc) became the first FDA-approved treatment in this setting. The decision was based on the AQUILA trial (NCT03301220), where the treatment achieved response rates of approximately 60%. By contrast, about 40% of patients still progressed at 5 years, with CR rates below 10%.

Against this backdrop, Nadeem noted that ImmunoPRISM explored whether teclistamab could be used earlier, when the immune system may be more fit, to potentially achieve deeper disease eradication. Eligible patients met the 20/2/20 high-risk criteria or had an International Myeloma Working Group risk score of 9 or greater, with additional high-risk features including evolving pattern, PETHEMA criteria, or high-risk cytogenetics.

After a 6-patient safety run-in, 59 total patients were enrolled and randomized 2:1 to teclistamab for 12 cycles or Len/Dex for 2 years. The median patient age was 65, approximately 50% had high-risk cytogenetics, and two-thirds met the 20/2/20 criteria.

Nadeem highlighted that teclistamab achieved a CR rate of 73% vs 0% with Len/Dex, meeting the primary end point. A very good partial response or better was reached in 86.7% of patients in the teclistamab arm vs 14.3% in the control arm.

At a median follow-up of 23.4 months, median PFS was not reached in either arm. However, the estimated 2-year PFS was 92% with teclistamab vs 51% with Len/Dex. Additionally, progression rates were 7% vs 36%, respectively. Minimal residual disease (MRD) negativity at 10^⁻⁵ was 81.2% in the teclistamab arm vs 0% in Len/Dex, and responses were sustained in all patients who achieved MRD at the time of data cutoff.

Regarding the safety profile, Nadeem acknowledged that it was generally manageable.

“Safety was overall favorable with no high-grade cytokine release syndrome events nor any neurological toxicities, and rates of grade 3 infections were the same between teclistamab and lenalidomide and dexamethasone at approximately 20%,” he concluded. “This number is lower than what is observed in patients with relapsed/refractory multiple myeloma.”