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