Daratumumab for post-ASCT maintenance treatment of myeloma

Daratumumab, a potent CD38-directed monoclonal antibody, has veritably transformed the treatment landscape of multiple myeloma. 1 Nooka AK Kaufman JL Hofmeister CC et al. Daratumumab in multiple myeloma. Cancer. 2019; 125: 2364-2382 Crossref PubMed Scopus (58) Google Scholar CASSIOPEIA, a two-part, phase 3 trial, has brought daratumumab to the forefront of efforts aimed at improving outcome for transplant-eligible patients. 2 Moreau P Attal M Hulin C et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 29-38 Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar Part 1 randomly assigned 1085 patients with newly diagnosed multiple myeloma to receive four pre-autologous stem-cell transplantation (ASCT) induction and two post-transplant consolidation cycles of bortezomib, thalidomide, and dexamethasone (VTd) alone, or in combination with daratumumab (D-VTd). D-VTd showed considerable improvement in depth of response and progression-free survival, leading to its regulatory approval. 2 Moreau P Attal M Hulin C et al. Bortezomib, thalidomide, and dexamethasone with or without daratumumab before and after autologous stem-cell transplantation for newly diagnosed multiple myeloma (CASSIOPEIA): a randomised, open-label, phase 3 study. Lancet. 2019; 394: 29-38 Summary Full Text Full Text PDF PubMed Scopus (346) Google Scholar An improved overall survival with D-VTd became apparent with longer follow-up. 3 Moreau P Hulin C Perrot A et al. Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trial. Lancet Oncol. 2021; (published online Sept 13.)https://doi.org/10.1016/S1470-2045(21)00428-9 Google Scholar A more contemporary regimen, D-VRd, involving lenalidomide, is awaiting mature data. 4 Voorhees PM Kaufman JL Laubach J et al. Daratumumab, lenalidomide, bortezomib, and dexamethasone for transplant-eligible newly diagnosed multiple myeloma: the GRIFFIN trial. Blood. 2020; 136: 936-945 Crossref PubMed Scopus (169) Google Scholar Maintenance with daratumumab or observation following treatment with bortezomib, thalidomide, and dexamethasone with or without daratumumab and autologous stem-cell transplant in patients with newly diagnosed multiple myeloma (CASSIOPEIA): an open-label, randomised, phase 3 trialDaratumumab maintenance every 8 weeks for 2 years significantly reduced the risk of disease progression or death compared with observation only. Longer follow-up and other ongoing studies will shed further light on the optimal daratumumab-containing post-ASCT maintenance treatment strategy. Full-Text PDF