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

Summary 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.