MRD-negative conversion with daratumumab monotherapy in newly diagnosed multiple myeloma patients in ≥VGPR/MRD-positive after first-line therapy: Final analysis of the open-label, single-arm multicentric phase 2 trial DART4MM

: Daratumumab is approved for front-line and relapsed myeloma therapy. Here, we evaluated daratumumab in multiple myeloma patients already in ≥very good partial response but minimal residual disease (MRD) positive by next-generation flow after first-line therapy and daratumumab naïve with the potential to eradicate the disease. In this prospective, single-arm phase 2 trial, we consecutively evaluated 110 eligible patients with newly diagnosed multiple myeloma for positivity at 10-6 in the bone marrow. Fifty patients were positive and were treated with 6 months of daratumumab. The primary end-point was at 6 months: MRD-negative patients stopped treatment, while positive patients continued for a total of 24 months. At the primary end-point, 15/50 (30%) patients became MRD negative. At 24 months, 11/50 (22%) patients were still MRD negative. At a median follow-up of 50 months, 29 (58%) patients relapsed. Median progression-free survival is reached at 45 months, and overall survival is not reached. Achieving at least one-time MRD negativity was significant (median progression-free survival of 61 vs. 26 months, p = 0.0009). Of 50 patients, 21 did not progress at a median time of 44 months (range 31-73) and four of the relapsed patients are still in duration of response, not treated yet.