# PERSEUS: daratumumab added to bortezomib-lenalidomide-dexamethasone around autologous transplant in newly diagnosed myeloma

Source: https://onco.cc/key-papers/paper-perseus-dara-vrd-transplant-nejm-2024/  
OnCo record `paper-perseus-dara-vrd-transplant-nejm-2024` (Key paper). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

Adding daratumumab to the standard three-drug induction, transplant and maintenance cut progression or death by 58% and pushed MRD-negativity to three-quarters of patients.

## Summary

PERSEUS randomised 709 transplant-eligible patients with newly diagnosed multiple myeloma to daratumumab plus bortezomib, lenalidomide and dexamethasone (D-VRd) induction and consolidation with daratumumab-lenalidomide maintenance, or VRd with lenalidomide maintenance. The primary endpoint was PFS. At 48 months PFS was 84.3% versus 67.7% (hazard ratio 0.42); complete response or better was 87.9% versus 70.1% and MRD-negativity at 10^-5 was 75.2% versus 47.5%. Daratumumab could be stopped after two years of maintenance in patients with sustained MRD-negativity. Grade 3-4 neutropenia, thrombocytopenia and infections were more frequent with daratumumab.

## Fields

- Kind: Key paper
- Last checked: 2026-09-08
- Journal: New England Journal of Medicine
- Year: 2024
- DOI: 10.1056/NEJMoa2312054
- Authors: Sonneveld P, Dimopoulos MA, Boccadoro M, et al.
- Findings: 709 transplant-eligible patients; D-VRd + D-R maintenance vs VRd + R maintenance.; 48-month PFS 84.3% vs 67.7%; hazard ratio 0.42.; Complete response or better 87.9% vs 70.1%.; MRD-negativity (10^-5) 75.2% vs 47.5%; sustained MRD-negativity over 12 months 64.8% vs 29.7%.; More grade 3-4 neutropenia (62.1% vs 51.0%) and infections with daratumumab.
- What it means: PERSEUS, with the earlier GRIFFIN and CASSIOPEIA trials, made a four-drug daratumumab quadruplet the standard for fit patients heading to transplant. It also introduced MRD-directed stopping of the antibody, a step towards treatment that is deep but not indefinite. Whether transplant itself remains necessary on top of a quadruplet is now the open question.
- Caveats: PFS, not overall survival, was the primary endpoint; OS follow-up is immature.; Both arms had autologous transplant, so it does not test transplant versus no transplant.; MRD-guided discontinuation applied only to daratumumab, not lenalidomide.; Younger, fitter patients than typical clinic populations.

## Sources

- Full text (DOI): https://doi.org/10.1056/NEJMoa2312054
- ClinicalTrials.gov NCT03710603: https://clinicaltrials.gov/study/NCT03710603

## Connected records

- pairings: [CD38 antibody added to PI-IMiD-dex (quadruplet induction)](https://onco.cc/pairings/cd38-plus-triplet/)
- cancers: [Multiple myeloma](https://onco.cc/cancers/multiple-myeloma/), [Newly diagnosed multiple myeloma, transplant-eligible](https://onco.cc/cancers/myeloma-transplant-eligible/)
- technologies: [Autologous stem cell transplant (high-dose therapy)](https://onco.cc/technologies/autologous-stem-cell-transplant/), [MRD / molecular residual disease testing](https://onco.cc/technologies/mrd-testing/)
- targets: [CD38](https://onco.cc/targets/cd38/)
- drugs: [Bortezomib](https://onco.cc/drugs/bortezomib/), [Daratumumab](https://onco.cc/drugs/daratumumab/), [Lenalidomide](https://onco.cc/drugs/lenalidomide/)
- companies: [Johnson & Johnson](https://onco.cc/companies/johnson-johnson/)
- terms: [MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶)](https://onco.cc/terms/mrd-negativity-myeloma/), [Progression-free survival (PFS)](https://onco.cc/terms/pfs/)
- trials: [PERSEUS](https://onco.cc/trials/perseus/)
- bottlenecks: [Dormant cells and minimal residual disease](https://onco.cc/bottlenecks/b-dormancy-mrd/), [Trial design, endpoints and cost](https://onco.cc/bottlenecks/b-trial-design/)
- journals: [New England Journal of Medicine](https://onco.cc/journals/nejm/)
- people: [Pieter Sonneveld](https://onco.cc/people/pieter-sonneveld/)

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