medwireNews: Supplementing the standard triplet regimen for newly diagnosed multiple myeloma with subcutaneous daratumumab significantly improves the outcomes of patients, shows the PERSEUS trial.
The first interim analysis of the phase 3 study for transplantation-eligible patients demonstrated that the quadruplet regimen achieved “a significant and clinically meaningful benefit with respect to progression-free survival [PFS], the occurrence of a complete response or better, and the occurrence of MRD [minimal residual disease]-negative status, with a favorable benefit–risk profile,” say the researchers.
For the study, the team recruited 709 transplantation-eligible patients with newly diagnosed multiple myeloma and randomly assigned them to receive up to six 28-day cycles of bortezomib, lenalidomide, plus dexamethasone– four induction cycles before stem-cell transplantation and two consolidation cycles after – followed by lenalidomide maintenance therapy either with or without the CD38-targeted agent daratumumab (D-VRd and VRd groups, respectively).
At a median follow-up of 47.5 months, the risk for progression or death was a significant 58% lower among participants who received daratumumab than those who did not. The estimated 48-month PFS rates were 84.3% and 67.7%, respectively.
A significantly higher proportion of patients in the D-VRd than VRd group achieved a complete response or stringent complete response, at 87.9% versus 70.1%, and this was also the case for MRD-negative status, defined as the absence of malignant cells at a sensitivity threshold of 10−5 plus at least a complete response, at 75.2% versus 47.5%.
Pieter Sonneveld (Erasmus MC Cancer Institute, Rotterdam, the Netherlands) and co-workers note that “the percentage of patients who had sustained MRD-negative status for at least 12 months in the D-VRd group was more than twice that in the VRd group,” at rates of 64.8% and 29.7%, respectively.
They continue: “Data regarding overall survival are immature; longer-term follow-up is ongoing.”
The researchers further report that “[t]he safety profile of daratumumab combined with VRd in the trial was consistent with the known safety profiles for daratumumab and VRd in this patient population.”
Grade 3 or 4 adverse events (AEs) occurred in 91.5% of patients in the D-VRd arm and 85.6% of those in the VRd arm, with the most common events of this severity being neutropenia (62.1 vs 51.0%), thrombocytopenia (29.1 vs 17.3%), diarrhea (10.5 vs 7.8%), pneumonia (10.5 vs 6.1%), and febrile neutropenia (9.4 vs 10.1%).
The incidence of serious AEs was higher in the D-VRd than VRd group, at 57.0% versus 49.3%, but the rate of discontinuation due to AEs and that of fatal AEs was lower, at 8.8% versus 21.3%, and 3.7% versus 4.6%, respectively.
“These results further strengthen the existing evidence supporting the use of daratumumab in combination regimens for patients with newly diagnosed multiple myeloma,” conclude Sonneveld and colleagues in The New England Journal of Medicine.
The PERSEUS data were simultaneously presented at the 65th ASH Annual Meeting & Exposition, held in San Diego, California, USA.
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N Engl J Med 2023; doi:10.1056/NEJMoa2312054
65th ASH Annual Meeting & Exposition; San Diego, California, USA: 9–12 December 2023