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.

Multiple myeloma (MM) is still considered an incurable disease, although much progress has been made in terms of responses and survivals.1,2 Innovative drugs can induce deeper responses with respect to the past, and complete re- sponse (CR) achievement is not sufficient anymore to tes- tify a durable response. 3 Minimal residual disease (MRD) status measured both by next-generation flow (NGF) and next-generation sequencing (NGS) is a consolidated new prognostic parameter in multiple myeloma trials, with a threshold at 10 −5 according to the International Myeloma Working Group (IMWG) guidelines.4–7 Recent trials have demonstrated that these techniques can reach even a higher sensitivity of 10 −6 , providing a greater discriminatory power for progression-free survival (PFS) and helping to identify true ‘functional cure’ or very long-term, treatment-free re- missions in multiple myeloma. 8 Daratumumab (Dara) is an IgG/k monoclonal antibody that binds selectively to CD38 on MM plasma cells (PC) and is now approved in various combination regimens for transplant-eligible (daratumumab, bortezomib, thalidomide, dexamethasone, Dara-VTd) and transplant-ineligible (dara- tumumab, lenalidomide, dexamethasone, Dara-Rd; daratu- mumab, bortezomib, melphalan, prednisone, Dara-VMP) newly diagnosed multiple myeloma.9,10 A consolidation therapy with bortezomib, thalidomide and dexamethasone (VTd) after autologous stem cell transplant (ASCT) has been reported in a randomized trial to increase the level of re- sponses measured by polymerase chain reaction (PCR),11–13 and recently, the randomized study CASSIOPEIA showed that daratumumab given as maintenance therapy every 8 weeks for 24 months after ASCT was superior to observa- tion in a population of MM patients treated with VTd with or without daratumumab as induction/consolidation.14,15 However, little is known about daratumumab monotherapy efficacy as consolidation/eradication therapy after a first line of therapy, if used in a very good responder group of patients with MRD positivity. Here, we present the results of the DART4MM study.