Daratumumab-Bortezomib-Thalidomide-Dexamethasone for Newly Diagnosed Myeloma: CASSIOPEIA Minimal Residual Disease Results

• Daratumumab-based induction/consolidation and maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS

• Daratumumab maintenance provided PFS benefit versus observation regardless of MRD status or prior induction/consolidation therapy

Previous results from CASSIOPEIA (NCT02541383) demonstrated superior progression-free survival (PFS) and minimal residual disease (MRD) negativity with the addition of daratumumab to bortezomib, thalidomide, and dexamethasone (VTd) induction/consolidation and with daratumumab maintenance versus observation in transplant-eligible newly diagnosed multiple myeloma (NDMM). Here, we present long-term MRD status and PFS outcomes after an 80.1-month median follow-up. Patients were randomly assigned (1:1) to daratumumab plus VTd (D-VTd) or VTd induction/consolidation; patients remaining on study were re-randomized to daratumumab maintenance or observation for £2 years. MRD status was assessed at pre-defined timepoints during each study phase. D-VTd improved overall MRD-negativity rates (10-5) post-induction (34.6% vs 23.1%; P<0.0001) and post-consolidation (63.7% vs 43.7%; P<0.0001) and provided PFS benefit, regardless of post-induction MRD status, versus VTd alone. Daratumumab maintenance improved overall MRD-negativity rates over observation, regardless of induction/consolidation treatment (D-VTd/daratumumab vs D-VTd/observation: 10-5, 77.3% vs 70.7% [P=0.0417]; 10-6, 60.7% vs 52.0% [P=0.0365]; VTd/daratumumab vs VTd/observation: 10-5, 70.9% vs 51.2% [P<0.0001]; 10-6, 48.4% vs 30.7% [P<0.0001]), and improved MRD-negativity rates, regardless of risk status, as defined by cytogenetic abnormalities or revised International Staging System score. Further, daratumumab maintenance provided PFS benefit versus observation, regardless of induction/consolidation treatment and post-consolidation MRD status. D-VTd followed by daratumumab maintenance consistently produced the highest landmark, accumulative, and sustained MRD-negativity rates (10-5 and 10-6), translating to superior long-term PFS outcomes. These results demonstrate that daratumumab-based induction/consolidation followed by daratumumab maintenance resulted in the deepest and most durable MRD negativity, leading to superior PFS outcomes.