New hopes and challenges have emerged in the management of patients with multiple myeloma (MM) after the approval of several new drugs and combinations during 2015, and new data presented during the 2016 American Society of Clinical Oncology (ASCO) meeting will further affect the way we treat patients with myeloma in the near future. One of the most promising new therapies is daratumumab (Dara), an anti-CD38 monoclonal antibody with notable single-agent activity in patients with relapsed and/or refractory (RR) MM that is also refractory to both proteasome inhibitors and immunomodulatory drugs. The CASTOR study1 is a prospective randomized trial of patients with RR MM who had received at least 1 prior line of therapy, and 30% were refractory to their last treatment. The CASTOR treatment group received combination treatment with Dara with bortezomib (Velcade; Millennium Pharmaceuticals Inc; bortezomib) and low-dose dexamethasone (Vd) (n = 251); the control group received only Vd therapy (n = 247). The DaraVd group showed a significant progression-free survival (PFS) advantage over the Vd group, with a 12-month PFS probability of 60.7% vs 26.9% corresponding to a significant reduction of disease progression or death probability of 61% (hazard ratio [HR], 0.39; 95% CI, 0.28-0.53; P < .001). This advantage was evident across all subgroups, including patients with stage ISS-3 disease (International Staging System), with prior autologous stem cell transplantation (ASCT) or with disease proven refractory to lenalidomide treatment. The PFS advantage was even higher when DaraVd was given as second-line therapy (1-year PFS probability, 77.5% vs 29.4%; HR, 0.31; P < .001). The overall response rate was also in favor of DaraVd (83% vs 63%; P < .0001; complete response, 19% vs 9%; P = .001; and MRD (minimal residual disease) negativity at the level of 10−4, 14% vs 3%). The most common adverse events with DaraVd were infusion-related reactions (associated with Dara), observed in 45% of patients (9% grade ≥3), mainly during the first DaraVd infusion. These results probably set DaraVd as a new standard of care for eligible patients with RR MM.