In November 2015, the U.S. Food and Drug Administration approved daratumumab for treatment of multiple myeloma in patients who had received at least three prior therapies. In May 2016 daratumumab was also conditionally approved by the European Medicines Agency for treatment of multiple myeloma. In November 2016, the FDA approved daratumumab in combination with lenalidomide or bortezomib and dexamethasone for the treatment of patients with multiple myeloma who have received at least one prior therapy. In May 2018, the FDA expanded the approval of daratumumab for use in combination with bortezomib, melphalan and prednisone to include the treatment of patients with newly diagnosed multiple myeloma who are ineligible for autologous stem cell transplant. The European Commission granted a marketing authorisation on 20 May 2016. In the European Union it is indicated as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor and an immunomodulatory agent and who have demonstrated disease progression on the last therapy.
Side effects
Treatment of multiple melanoma with daratumumab typically results in bacterial and viral infections due to the killing of natural killer cells. Daratumumab frequently causes human cytomegalovirus reactivation by an unknown mechanism. Infection related reactions are also common.
Daratumumab can also bind to CD38 present on red blood cells and interfere with routine testing for clinically significant antibodies. Patients will show a panreactive antibody panel, including a positive auto-control, which tends to mask the presence of any clinically significant antibodies. Treatment of the antibody panel cells with dithiothreitol and repeating testing will effectively negate the binding of daratumumab to CD38 on the red blood cell surface; however, DTT also inactivates/destroys many antigens on the red blood cell surface by disrupting disulfide bonds. The only antigen system affected that is associated with common, clinically significant antibodies is Kell, making crossmatch testing with K-negative RBCs a reasonable alternative when urgent transfusion is indicated. It is therefore advisable to do a baseline antibody screen and Rh & Kell phenotyping before starting the therapy. If antibody screen is negative, proceed with phenotype matched transfusions during therapy. If antibody screen is positive, give specific antigen negative blood. The incompatibility may persist for up to 6 months after stopping the medicine. Furthermore, blood transfusion centers should be routinely notified when sending such a sample. Interaction with flow cytometry testing Daratumumab can also interfere with flow cytometric evaluation of multiple myeloma, causing an apparent lack of plasma cells.
Encouraging preliminary results were reported in June 2012 from a Phase 1/2 clinical trial in relapsed multiple myeloma patients. Updated trial results presented in December 2012 indicate daratumumab is continuing to show promising single-agent anti-myeloma activity. A 2015 study compared monotherapy 8 and 16 mg/kg at monthly to weekly intervals. Daratumumab was given priority review status by the FDA for multiple myeloma as a combination therapy. Daratumumab phase 3 trials for multiple myeloma show great promise in combination therapy with lenalidomide and dexamethasone as well as with bortezomib and dexamethasone.
