Daratumumab-based quadruplet for patients with extramedullary multiple myeloma: Results from the Phase II prospective EMN19 study

Novel therapies are needed for patients with multiple myeloma (MM) and extramedullary plasmacytomas. The prospective, Phase II EMN19 study assessed the efficacy and safety of daratumumab plus bortezomib, cyclophosphamide, and dexamethasone (DaraVCD) in 40 patients with newly diagnosed MM (NDMM; n = 29) or at first relapse (RMM; n = 11) and positron emission tomography or computed tomography (PET/CT)-confirmed extramedullary plasmacytomas (extraosseous [EMD] and/or paraosseous [PS]). DaraVCD was administered until disease progression or up to 3 years. The primary endpoint was hematological complete response (CR). Among patients, 22 (55.0%), 4 (10.0%), and 14 (35.0%) had EMD, EMD/PS, and PS plasmacytomas, respectively. Median patient age was 58.0 years, and 16 (40.0%), 12 (30.0%), and 10 (25.0%) patients were at International Staging System (ISS) Stages I, II, and III, respectively. Median circulating tumor cell (CTC) level was 0.002% (range, 0.000–0.353), significantly higher (P < 0.05) in patients with ISS Stage III and those with plasma cells > 60%. At a median follow-up of 30.0 months, all patients completed treatment (median duration: 19.8 months). The overall hematologic ≥CR rate was 47.5% (19/40; NDMM patients: 58.6% [17/29]; RMM patients: 18.2% [2/11]). Of patients with ≥CR, 80.0% (15/19) achieved minimal residual disease (MRD) negativity, and 68.4% (13/19) combined MRD negativity and complete metabolic response (CMR) on PET/CT. The overall median progression-free survival was 25.8 months, significantly longer in patients achieving hematologic ≥CR and/or CMR than others (not reached and 4.8 months, respectively; P < 0.001). DaraVCD showed encouraging efficacy in patients with MM and extramedullary plasmacytomas. Notably, this is the first report on CTC levels in EMD, and they were lower than previously reported NDMM thresholds.