BACKGROUND: In our efforts to develop novel effective treatment regimens for multiple myeloma we evaluated the potential benefits of combining the immunomodulatory drug lenalidomide with daratumumab. Daratumumab is a novel human CD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis. DESIGN AND METHODS: To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells. We also tested the effect of lenalidomide on daratumumab-dependent cell-mediated-cytotoxicity and complement-dependent cytotoxicity of multiple myeloma cells directly in the bone marrow mononuclear cells of multiple myeloma patients. Finally, we determined the daratumumab-dependent cell-mediated cytotoxicity using peripheral blood mononuclear cells of multiple myeloma patients receiving lenalidomide treatment. RESULTS: Daratumumab-dependent cell-mediated cytotoxicity of purified primary multiple myeloma cells, as well as of the UM-9 cell line, was significantly augmented by lenalidomide pre-treatment of the effector cells derived from peripheral blood mononuclear cells from healthy individuals. More importantly, we demonstrated a clear synergy between lenalidomide and daratumumab-induced antibody-dependent cell-mediated cytotoxicity directly in the bone marrow mononuclear cells of multiple myeloma patients, indicating that lenalidomide can also potentiate the daratumumab-dependent lysis of myeloma cells by activating the autologous effector cells within the natural environment of malignant cells. Finally, daratumumab-dependent cell-mediated cytotoxicity was significantly up-regulated in peripheral blood mononuclear cells derived from 3 multiple myeloma patients during lenalidomide treatment. CONCLUSIONS: Our results indicate that powerful and complementary effects may be achieved by combining lenalidomide and daratumumab in the clinical management of multiple myeloma.
BACKGROUND: In our efforts to develop novel effective treatment regimens for multiple myeloma we evaluated the potential benefits of combining the immunomodulatory drug lenalidomide with daratumumab. Daratumumab is a novel humanCD38 monoclonal antibody which kills CD38+ multiple myeloma cells via antibody-dependent cell-mediated cytotoxicity, complement-dependent cytotoxicity and apoptosis. DESIGN AND METHODS: To explore the effect of lenalidomide combined with daratumumab, we first carried out standard antibody-dependent cell-mediated cytotoxicity and complement-dependent cytotoxicity assays in which the CD38+ multiple myeloma cell line UM-9 and primary multiple myeloma cells isolated from patients were used as target cells. We also tested the effect of lenalidomide on daratumumab-dependent cell-mediated-cytotoxicity and complement-dependent cytotoxicity of multiple myeloma cells directly in the bone marrow mononuclear cells of multiple myelomapatients. Finally, we determined the daratumumab-dependent cell-mediated cytotoxicity using peripheral blood mononuclear cells of multiple myelomapatients receiving lenalidomide treatment. RESULTS:Daratumumab-dependent cell-mediated cytotoxicity of purified primary multiple myeloma cells, as well as of the UM-9 cell line, was significantly augmented by lenalidomide pre-treatment of the effector cells derived from peripheral blood mononuclear cells from healthy individuals. More importantly, we demonstrated a clear synergy between lenalidomide and daratumumab-induced antibody-dependent cell-mediated cytotoxicity directly in the bone marrow mononuclear cells of multiple myelomapatients, indicating that lenalidomide can also potentiate the daratumumab-dependent lysis of myeloma cells by activating the autologous effector cells within the natural environment of malignant cells. Finally, daratumumab-dependent cell-mediated cytotoxicity was significantly up-regulated in peripheral blood mononuclear cells derived from 3 multiple myelomapatients during lenalidomide treatment. CONCLUSIONS: Our results indicate that powerful and complementary effects may be achieved by combining lenalidomide and daratumumab in the clinical management of multiple myeloma.
Authors: F Malavasi; A Funaro; M Alessio; L B DeMonte; C M Ausiello; U Dianzani; F Lanza; E Magrini; M Momo; S Roggero Journal: Int J Clin Lab Res Date: 1992
Authors: Meisam Naeimi Kararoudi; Yuya Nagai; Ezgi Elmas; Marcelo de Souza Fernandes Pereira; Syed Abbas Ali; Philip Hollingsworth Imus; Darren Wethington; Ivan Marques Borrello; Dean Anthony Lee; Gabriel Ghiaur Journal: Blood Date: 2020-11-19 Impact factor: 22.113
Authors: Alba Matas-Céspedes; Anna Vidal-Crespo; Vanina Rodriguez; Neus Villamor; Julio Delgado; Eva Giné; Heleia Roca-Ho; Pablo Menéndez; Elías Campo; Armando López-Guillermo; Dolors Colomer; Gaël Roué; Adrian Wiestner; Paul W H I Parren; Parul Doshi; Jeroen Lammerts van Bueren; Patricia Pérez-Galán Journal: Clin Cancer Res Date: 2016-09-16 Impact factor: 12.531
Authors: I S Nijhof; R W J Groen; H M Lokhorst; B van Kessel; A C Bloem; J van Velzen; R de Jong-Korlaar; H Yuan; W A Noort; S K Klein; A C M Martens; P Doshi; K Sasser; T Mutis; N W C J van de Donk Journal: Leukemia Date: 2015-05-15 Impact factor: 11.528
Authors: T Vaisitti; V Audrito; S Serra; R Buonincontri; G Sociali; E Mannino; A Pagnani; A Zucchetto; E Tissino; C Vitale; M Coscia; C Usai; C Pepper; V Gattei; S Bruzzone; S Deaglio Journal: Leukemia Date: 2014-07-03 Impact factor: 11.528