High‑risk smoldering multiple myeloma (HR‑SMM) is an asymptomatic plasma‑cell disorder with genomic and clinical features that confer elevated risk of progression to symptomatic multiple myeloma. Approaches to immune interception in precursor states aim to prevent or delay progression by eliminating clonal plasma cells while patients retain a more functional immune compartment than in relapsed disease.
Teclistamab is a bispecific T‑cell engager that targets B cell maturation antigen (BCMA) on plasma cells and redirects T cells to mediate cytotoxicity. In relapsed or refractory multiple myeloma (RRMM), teclistamab has shown clinically meaningful activity, and combination and earlier‑line studies have suggested greater efficacy when used before extensive prior therapy. The ImmunoPRISM randomized phase 2 trial evaluated whether fixed‑duration single‑agent teclistamab could provide superior disease control compared with a standard immunomodulatory regimen, lenalidomide–dexamethasone (Rd), in patients with HR‑SMM.
ImmunoPRISM was a randomized phase 2 study that began with a six‑patient safety run‑in to assess initial tolerability of teclistamab in the HR‑SMM population. After the run‑in, patients were randomized in a 2:1 ratio to receive either fixed‑duration teclistamab or Rd. The trial’s primary endpoint was the rate of complete response (CR). Key secondary outcomes reported included minimal residual disease (MRD) negativity at 10−5, progression‑free survival (PFS), duration of response and time to progression (TTP), as well as safety and adverse event profiles.
Details such as the precise dosing schedules, duration of fixed‑duration therapy, stratification factors used for randomization, and full statistical analysis plan were not reported in the source material provided.
As of the data cut‑off on 26 May 2026, a total of 59 patients had been treated in the trial: 45 in the teclistamab arm and 14 in the Rd arm. The source material does not provide a full breakdown of patient demographics, comorbidities, cytogenetic or molecular risk features, or prior therapies (if any), nor does it report baseline laboratory values or performance‑status distributions. The six‑patient safety run‑in preceded randomization.
Teclistamab produced markedly higher rates of deep responses compared with Rd in this HR‑SMM cohort. The reported outcomes include:
Complete response (CR): 77.8% in the teclistamab arm versus 0% in the Rd arm (primary endpoint).
MRD at 10−5: MRD negativity was observed in 82.2% of patients treated with teclistamab.
Progression‑free survival (PFS): At a median follow‑up of 24.5 months, 2‑year PFS was 92% with teclistamab compared with 49% with Rd.
Other efficacy measures: The authors report that overall response rates, duration of response and time to progression were significantly improved with teclistamab compared with Rd; specific numeric values for overall response rate and median duration of response or TTP were not provided in the source text.
These results indicate that fixed‑duration single‑agent teclistamab achieved high rates of deep and durable disease control in this high‑risk precursor population within the reported follow‑up period.
Safety findings for teclistamab in HR‑SMM were described as manageable in the trial report. Key safety observations included:
Cytokine release syndrome (CRS): Predominantly grade 1–2 events were reported in the teclistamab arm.
Neurotoxicity: No neurotoxic events were reported in the teclistamab arm in the provided data.
Infections: The incidence of grade 3 infections was similar between arms—20% with teclistamab versus 21% with Rd.
Mortality: No deaths occurred in either treatment arm during the reported follow‑up interval.
The source did not provide a detailed adverse‑event table, time to onset/duration of CRS events, management strategies, or long‑term immune‑related safety signals beyond the items summarized above.
The ImmunoPRISM phase 2 randomized comparison suggests that earlier use of a BCMA‑directed bispecific antibody can induce high rates of CR and MRD negativity and substantially improve 2‑year PFS compared with Rd in HR‑SMM. These outcomes support the concept of immune interception in precursor states, leveraging a more intact immune system to achieve deeper disease eradication than that observed with therapy in later‑line RRMM.
Limitations based on the provided report include the relatively small total sample size (59 patients), the imbalance inherent to a 2:1 randomization, and incomplete reporting in the source of detailed baseline characteristics, full efficacy numeric tables beyond the primary outcomes, and longer‑term follow‑up data. As with any early randomized phase 2 finding, confirmation in larger cohorts and longer observation will be important to define durability, long‑term safety, and potential effects on overall survival and progression to symptomatic myeloma.
The trial is registered at ClinicalTrials.gov under identifier NCT05469893. The article reporting these randomized phase 2 results was published in Nature Medicine; the cited published date in the source is 11 September 2026. For further details such as full methods, statistical analyses, and complete safety and efficacy tables, consult the full publication and associated supplementary materials.