EMA Review of Daratumumab for the Treatment of Adult Patients with Multiple Myeloma.

On May 20, 2016, a conditional marketing authorization valid through the European Union (EU) was issued for daratumumab as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, whose prior therapy included a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD) and who had demonstrated disease progression on the last therapy. The review of daratumumab was conducted under the EMA's accelerated assessment program for drugs that are of major interest for public health, especially from the point of view of therapeutic innovation.Daratumumab monotherapy achieved an overall response rate of 29.2% (95% confidence interval [CI] 20.8 to 38.9) in patients with multiple myeloma who had received at least three prior lines of therapy (including a PI and IMiD) or were double refractory to a PI and an IMiD (Study MMY2002). In patients with multiple myeloma relapsed from or refractory to two or more different prior therapies, including IMiDs (e.g., thalidomide, lenalidomide) and PI, an overall response was observed in 15 patients (35.7%, 95% CI: 21.6 to 52.0) (Study GEN501).On April 28, 2017, the therapeutic indication was extended to include the use of daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of adult patients with multiple myeloma who have received at least one prior therapy. This was based on two subsequent phase III studies of daratumumab in combination with lenalidomide/low-dose dexamethasone (MMY3003) and bortezomib/low dose dexamethasone (MMY3004).The most common side effects (grade 3-4) associated with daratumumab included neutropenia (37%), thrombocytopenia (23%), anemia (16%), pneumonia (10%), lymphopenia (8%), infusion-related reactions (6%), upper respiratory tract infection (5%), and fatigue (5%).The objective of this study was to summarize the scientific review done by the CHMP of the application leading to regulatory approval in the EU. The full scientific assessment report and product information, including the Summary of Product Characteristics (SmPC), are available on the EMA website (www.ema.europa.eu). IMPLICATIONS FOR PRACTICE: A conditional Marketing authorization was issued in the European Union for daratumamb as monotherapy for the treatment of adult patients with relapsed and refractory multiple myeloma, based on the response rate data from two single-agent studies. Darzalex, a novel monoclonal antibody targeted against CD38, demonstrated a durable response rate in a heavily pre-treated population with limited treatment options based on the response rate data from two single-agent studies. The addition of daratumumab to lenalidomide and dexamethasone (study MMY3003), or bortezomib and dexamethasone (MMY3004), demonstrated a positive effect on progression-free survival in patients with multiple myeloma who had received at least one prior therapy. Following submission of the controlled data of the MMY3003 and MMY3004 studies, the efficacy and safety of daratumumab was confirmed and the approval of daratumumab was converted to standard approval.