# AQUILA: daratumumab versus active monitoring in high-risk smouldering multiple myeloma

Source: https://onco.cc/key-papers/paper-aquila-daratumumab-smouldering-nejm-2025/  
OnCo record `paper-aquila-daratumumab-smouldering-nejm-2025` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Giving daratumumab for up to three years to people with high-risk smouldering myeloma roughly halved the risk of progressing to active myeloma or death compared with watching and waiting.

## Summary

Phase 3 trial of 390 patients with high-risk smouldering multiple myeloma randomised to subcutaneous daratumumab monotherapy for up to 36 months or active monitoring.

Five-year progression-free survival was 63.1 percent with daratumumab against 40.8 percent with monitoring (hazard ratio 0.49), with a favourable trend in overall survival and a manageable toxicity profile.

## Fields

- Kind: Key paper
- Last checked: 2026-09-17
- Journal: New England Journal of Medicine
- Year: 2025
- DOI: 10.1056/NEJMoa2409029
- Authors: Dimopoulos MA, Voorhees PM, Schjesvold F, et al.
- Findings: Five-year progression-free survival 63.1 percent vs 40.8 percent; hazard ratio 0.49.; Five-year overall survival 93.0 percent vs 86.9 percent.
- What it means: Early single-agent treatment of high-risk smouldering myeloma is now an option with regulatory approval, though monitoring remains acceptable and the definition of high risk matters.
- Caveats: Risk definitions at enrolment predate the 20/2/20 model, so some patients were lower risk than intended.; Whether early treatment improves survival compared with treating at progression remains unproven.

## Sources

- N Engl J Med 2025: https://doi.org/10.1056/NEJMoa2409029
- PubMed: https://pubmed.ncbi.nlm.nih.gov/39652675/

## Connected records

- cancers: [Smouldering multiple myeloma](https://onco.cc/cancers/smouldering-myeloma/)
- drugs: [Daratumumab](https://onco.cc/drugs/daratumumab/)
- trials: [AQUILA](https://onco.cc/trials/aquila/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)

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