ORIGINAL ARTICLE Single-agent daratumumab in very advanced relapsed and refractory multiple myeloma patients: a real-life single-center retrospective study Maxime Jullien 1 & Sabrina Trudel 1 & Benoit Tessoulin 1,2 & Béatrice Mahé 1 & Viviane Dubruille 1 & Nicolas Blin 1 & Thomas Gastinne 1 & Antoine Bonnet 1 & Anne Lok 1 & Amandine Lebourgeois 1 & Pierre Peterlin 1 & Alice Garnier 1 & Patrice Chevalier 1 & Thierry Guillaume 1 & Patrick Thomaré 3 & Steven Le Gouill 1,2,4 & Philippe Moreau 1,2,4 & Cyrille Touzeau 1,2,4 Received: 24 January 2019 /Accepted: 2 March 2019 # Springer-Verlag GmbH Germany, part of Springer Nature 2019 Abstract The anti-CD38 monoclonal antibody daratumumab is approved as a single agent for the treatment of patients with relapsed and refractory multiple myeloma (RRMM) who have received at least three prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory agent (IMID), or who are double refractory to a PI and an IMID. To date, no real-life data on the efficacy and tolerance of daratumumab in this setting are available. We report here the results of a single-center series of 41 RRMM patients treated with single-agent daratumumab outside clinical trials. Patients received a median number of 4 prior therapies. All patients were previously exposed to PI and IMID and all patients were refractory to the last line of therapy. Most patients presented with high-risk characteristics, including 24% adverse cytogenetics (del17p/t(4,14)), 31% extramedullary disease and 12% circulating plasmacytosis at time of daratumumab therapy. The overall response rate was 24%, including 5% very good partial response or better. After a median follow-up of 6.5 months, all patients experienced disease relapse. The median progression-free survival was 1.9 months. At the time of disease progression, 44% of patients did not receive subsequent therapy. The median overall survival was 6.5 months. No new safety signal was identified. These real-life results revealed modest efficacy of single-agent daratumumab in advanced patients with RRMM in comparison with data from clinical trials. Keywords Daratumumab . Multiple myeloma . Real life Introduction The outcome of myeloma patients has been dramatically im- proved over the past decades [1]. This outstanding improve- ment is predominantly due to the widespread use of novel agents, including proteasome inhibitors (PI) and immuno- modulatory drugs (IMID). However, the outcome of patients whose disease became refractory to PI and IMID remains poor, with a median overall survival (OS) of nearly 1 year [2]. In the past years, immunotherapy emerged as a major class for the treatment of multiple myeloma patients [3]. Daratumumab, a fully human monoclonal IgGk antibody targeting CD38, was the first monoclonal antibody that dem- onstrated single agent clinical activity in myeloma patients [4, 5]. Daratumumab was approved by the American Food and Drug Agency (FDA) in 2015 for the treatment of patients with * Cyrille Touzeau cyrille.touzeau@chu-nantes.fr 1 Service d’hématologie Clinique, Centre Hospitalier Universitaire, Nantes, France 2 CRCINA, INSERM, CNRS, Université d’Angers, Université de Nantes, Nantes, France 3 Pharmacie Clinique Oncologique, Centre Hospitalier Universitaire, Nantes, France 4 Site de Recherche Intégrée sur le Cancer (SIRIC) « ILIAD », Nantes, France Annals of Hematology https://doi.org/10.1007/s00277-019-03655-5