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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.
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.
Shares MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), CD38, Daratumumab, Bortezomib.
Shares CD38 antibody added to PI-IMiD-dex (quadruplet induction), MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), CD38, Daratumumab.
Shares PERSEUS, MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), Newly diagnosed multiple myeloma, transplant-eligible, Daratumumab.
Shares CD38 antibody added to PI-IMiD-dex (quadruplet induction), Daratumumab, Bortezomib, Lenalidomide.
Shares Newly diagnosed multiple myeloma, transplant-eligible, Daratumumab, Lenalidomide, Johnson & Johnson.
Shares Newly diagnosed multiple myeloma, transplant-eligible, Daratumumab, Bortezomib, Lenalidomide.
Shares Daratumumab, Bortezomib, Lenalidomide, Johnson & Johnson.
Shares MRD negativity (myeloma, 10⁻⁵ / 10⁻⁶), Daratumumab, Bortezomib, Progression-free survival (PFS).