Daratumumab in high-risk MGUS and low-risk smoldering myeloma: results of the Phase II D-PRISM study
Mené sur 41 patients présentant une gammapathie monoclonale de signification indéterminée à haut risque d'évolution ou atteints d'un myélome multiple indolent à faible risque d'évolution, cet essai de phase II évalue l'efficacité, du point de vue du taux de réponse, et la toxicité du daratumumab
Daratumumab is approved for patients with multiple myeloma (MM) and high-risk smoldering MM (HR-SMM). However, HR-SMM is often as genomically complex as MM, suggesting it may be too advanced for single-agent intervention. We report on a Phase II trial of single-agent daratumumab in patients with earlier-stage disease, including high-risk monoclonal gammopathy of undetermined significance and low-risk SMM, to test if earlier treatment can induce deep responses and prevent progression to MM (D-PRISM/NCT03236428, n = 41). As primary outcome, the rate of Very Good Partial Response or better is 17% (95% CI: 7–32), which is comparable to what was observed in HR-SMM and does not meet the study’s primary endpoint. The overall response rate is 54%, with two patients developing MM and 51% biochemical progression. Grade 3 or higher toxicities include hypertension (7%), diarrhea (2%), flu-like symptoms (2%), and headache (2%). Genomic and immune variables associated with biochemical progression are identified in exploratory analyses leveraging whole-genome and single-cell RNA-sequencing. This study demonstrates that, although less effective than expected, daratumumab is safe and can induce deep responses in certain early-stage patients, highlighting the importance of adopting genomic and immune profiling to improve patient selection and maximize the benefit/risk ratio in trials of early intervention.
Nature Communications , article en libre accès, 2026