Daratumumab combinations for patients with newly diagnosed and relapsed multiple myeloma.

Survival outcomes for patients with multiple myeloma continue to improve with the incorporation of newer treatment modalities. Using standard triplet induction with lenalidomide, bortezomib, and dexamethasone (RVd) before autologous haematopoietic stem-cell transplantation (HSCT), median overall survival is now approximately 10 years. 1 Joseph NS Kaufman JL Dhodapkar MV et al. Long-term follow-up results of lenalidomide, bortezomib, and dexamethasone induction therapy and risk-adapted maintenance approach in newly diagnosed multiple myeloma. J Clin Oncol. 2020; 38: 1928-1937 Crossref PubMed Scopus (113) Google Scholar Daratumumab is an IgG1κ human monoclonal antibody that binds to CD38, eliciting myeloma cell death through various direct immunological mechanisms as well as modulation of the immunosuppressive microenvironment. However, to incorporate this treatment into routine care, well designed randomised clinical trials with adequate follow-up are required. For newly diagnosed patients with multiple myeloma, daratumumab in combination with bortezomib, thalidomide, and dexamethasone (D-VTd) has become standard of care in many countries following the progression-free survival benefit shown in the CASSIOPEIA trial. 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 (532) Google Scholar For transplantation-ineligible patients, daratumumab plus lenalidomide and dexamethasone has shown an overall survival benefit over lenalidomide and dexamethasone and is widely accepted to be the gold standard. In the relapse setting, positive results have also been observed when combined with lenalidomide, bortezomib or carfilzomib. Similar findings have been observed with isatuximab, another CD38 monoclonal antibody. In The Lancet Haematology, results of two further randomised controlled trials evaluating the addition of daratumumab to standard-of-care regimens are reported. Subcutaneous daratumumab plus pomalidomide and dexamethasone versus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma (APOLLO): extended follow up of an open-label, randomised, multicentre, phase 3 trialAlthough the difference in overall survival observed between treatment groups was not significant, the safety profile results with long-term follow-up reported here continue to support the use of daratumumab plus pomalidomide and dexamethasone in patients with relapsed or refractory multiple myeloma. Full-Text PDF Addition of daratumumab to lenalidomide, bortezomib, and dexamethasone for transplantation-eligible patients with newly diagnosed multiple myeloma (GRIFFIN): final analysis of an open-label, randomised, phase 2 trialAddition of daratumumab to RVd improved the depth of response and progression-free survival in transplantation-eligible patients with newly diagnosed multiple myeloma. These results justify further evaluation in phase 3 studies. Full-Text PDF