Recent results from the phase III AQUILA trial demonstrate the benefit of fixed-duration monotherapy with daratumumab over observation in patients with high-risk smouldering multiple myeloma, which changes the early interception treatment landscape. Herein, we discuss how future studies could build on this success and pave the way to eradicating multiple myeloma before it starts.
This is a preview of subscription content, access via your institution
Access options
Access Nature and 54 other Nature Portfolio journals
Get Nature+, our best-value online-access subscription
$32.99 / 30 days
cancel any time
Subscribe to this journal
Receive 12 print issues and online access
$189.00 per year
only $15.75 per issue
Rent or buy this article
Prices vary by article type
from$1.95
to$39.95
Prices may be subject to local taxes which are calculated during checkout
References
Ghobrial, I. M. et al. Round table discussion on optimal clinical trial design in precursor multiple myeloma. Blood Cancer Discov. 5, 146–152 (2024).
Mateos, M. V. et al. International Myeloma Working Group risk stratification model for smoldering multiple myeloma (SMM). Blood Cancer J. 10, 102 (2020).
Lakshman, A. et al. Risk stratification of smoldering multiple myeloma incorporating revised IMWG diagnostic criteria. Blood Cancer J. 8, 59 (2018).
Cowan, A. et al. Personalised progression prediction in patients with monoclonal gammopathy of undetermined significance or smouldering multiple myeloma (PANGEA): a retrospective, multicohort study. Lancet Haematol. 10, e203–e212 (2023).
Dutta, A. K. et al. MinimuMM-seq: genome sequencing of circulating tumor cells for minimally invasive molecular characterization of multiple myeloma pathology. Cancer Discov. 13, 348–363 (2023).
Mateos, M. V. et al. Lenalidomide-dexamethasone versus observation in high-risk smoldering myeloma after 12 years of median follow-up time: a randomized, open-label study. Eur. J. Cancer 174, 243–250 (2022).
Lonial, S. et al. Randomized trial of lenalidomide versus observation in smoldering multiple myeloma. J. Clin. Oncol. 38, 1126–1137 (2020).
Dimopoulos, M. A. et al. Daratumumab or active monitoring for high-risk smoldering multiple myeloma. N. Engl. J. Med. https://doi.org/10.1056/NEJMoa2409029 (2024).
Nadeem, O. et al. Immuno-PRISM: a randomized phase II platform study of bispecific antibodies in high-risk smoldering myeloma. Blood 142 (Suppl. 1), 206 (2023).
Nadeem, O. et al. Early safety and efficacy of CAR-T cell therapy in precursor myeloma: results of the CAR-PRISM study using ciltacabtagene autoleucel in high-risk smoldering myeloma. Blood 144 (Suppl. 1), 1027 (2024).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Competing interests
O.N. has received research support from Janssen and Takeda; has been an advisory board member for Bristol Myers Squibb, GPCR therapeutics, Janssen, Sanofi and Takeda; and has received honoraria from Pfizer. I.M.G. has been a paid consultant for 10X Genomics, AbbVie, Adaptive Biotechnologies, Amgen, Aptitude Health, Binding Site (part of Thermo Fisher Scientific), Bristol Myers Squibb, GlaxoSmithKline, Janssen, Menarini Silicon Biosystems, Novartis, Pfizer, Regeneron, Sanofi, Standard Biotools, and Takeda. She is a founder and board member of, and holds private equity in, Predicta Biosciences; and her spouse is the chief medical officer of, and holds private equity in, Disc Medicine.
Rights and permissions
About this article
Cite this article
Nadeem, O., Ghobrial, I.M. Early intervention with daratumumab improves survival for patients with high-risk smouldering myeloma. Nat Rev Clin Oncol 22, 159–160 (2025). https://doi.org/10.1038/s41571-025-00987-2
Published:
Version of record:
Issue date:
DOI: https://doi.org/10.1038/s41571-025-00987-2
