In patients with transplant-ineligible newly diagnosed multiple myeloma ( NDMM ), Daratumumab ( Darzalex ) has reduced the risk of disease progression or death by 44% in MAIA ( Daratumumab / Lenalidomide / Dexamethasone; D-Rd ) and 58% in ALCYONE ( Daratumumab / Bortezomib / Melphalan / Prednisone; D-VMP ).
Minimal residual disease ( MRD ) is a sensitive measure of disease and response to therapy. MRD-negativity status and durability were assessed in MAIA and ALCYONE.
MRD assessments using next-generation sequencing ( 10-5 ) occurred for patients achieving complete response ( CR ) or better, and after greater than or equal to complete response at 12, 18, 24, and 30 months from the first dose.
Progression-free survival ( PFS ) by MRD status and sustained MRD negativity lasting 6 or more and 12 or more months were analyzed in the intent-to-treat population and among patients achieving greater than or equal to complete response.
In MAIA, ( D-Rd, n=368; Rd, n=369 ), and ALCYONE ( D-VMP, n=350; VMP, n=356 ), the median duration of follow-up was 36.4 months and 40.1 months, respectively. MRD-negative status and sustained MRD negativity lasting 6 or more and 12 or more months were associated with improved progression-free survival, regardless of treatment group.
However, Daratumumab-based therapy has improved rates of MRD negativity lasting 6 or more months ( D-Rd, 14.9% vs Rd, 4.3%; D-VMP, 15.7% vs VMP, 4.5% ) and 12 or more months ( D-Rd, 10.9% vs Rd, 2.4%; D-VMP, 14.0% vs VMP, 2.8% ), both of which translated to improved progression-free survival versus control groups.
In a pooled analysis, patients who were MRD negative had improved progression-free survival versus patients who were MRD positive.
Patients with newly diagnosed multiple myeloma who achieved MRD-negative status or sustained MRD negativity had deep remission and improved clinical outcomes. ( Xagena )
San-Miguel JF et al, Blood 2021; Online ahead of print