First line treatment in line with stem cell transplantation of the newly diagnosed multiple myeloma! The darzalex + VTD scheme of Johnson & Johnson has been recommended and approved by the European Union CHMP!

December 15, 2019 / BIOON / -- Janssen Pharmaceutical, a subsidiary of JNJ, recently announced that the European Drug Administration (EMA) human pharmaceutical products Committee (CHMP) has issued active review opinions and recommended approval of darzalex The existing marketing authorization of (daratumumab) is included in the first line treatment of newly diagnosed multiple myeloma (MM) patients who meet the conditions of self stem cell transplantation (ASCT), combined with three drug regimens (VTd) of bortezomib, thalidomide and dexamethasone (Zomi) The CHMP's comments will now be reviewed by the European Commission (EC), which is expected to make a final approval decision in the coming months In the United States, the darzalex VTD program was approved by the FDA at the end of September this year, and the first-line treatment for newly diagnosed MM patients who meet the ASCT conditions It is worth mentioning that darzalex is the first and only biological agent approved by FDA to be used in newly diagnosed MM patients eligible for stem cell transplantation The indication was approved through a priority review process, marking darzalex's seventh indication in less than four years of us regulation and the third indication for the treatment of newly diagnosed MM patients CHMP recommends the approval of darzalex VTD protocol based on the data of Cassiopeia (mmy3006) phase III clinical study This is a randomized, open label, multicenter study involving 1085 newly diagnosed MM patients eligible for high-dose chemotherapy and stem cell transplantation In the first part of the study, patients were randomly divided into two groups: one group received VTD induction therapy, high-dose chemotherapy, ASCT and VTD consolidation therapy; the other group received darzalex + VTD induction therapy, high-dose chemotherapy, ASCT and darzalex + VTD consolidation therapy The main end point of this part of the study was the proportion of patients who obtained strict complete remission (SCR) at the end of consolidation therapy Patients with partial or better remission in the first part of the study entered the second part of the study and were randomly assigned for a second time During a period of up to 2 years, they received darzalex (16 mg / kg, once every 8 weeks) maintenance treatment, or only observed no further treatment The main end point of this part of the study was progression free survival (PFS) The results showed that the first part of the study reached the primary end point: at the end of consolidation treatment, a significantly higher proportion of patients in the darzalex VTD group achieved strict complete remission compared with the VTD group (SCR: 29% vs 20%; or = 1.60, 95% CI: 1.21-2.12, P = 0.0010) After a median follow-up of 18.8 months, the risk of disease progression or death in the darzalex VTD group was significantly reduced by 53% (HR = 0.47; 95% CI: 0.33-0.67, P < 0.0001), compared with that in the VTD group Compared with VTD, darzalex VTD also improved complete or better remission rate (39% vs 26%, or = 1.82, 95% CI: 1.40-2.36) and very good partial or better remission rate (83% vs 78%, or = 1.41, 95% CI: 1.04-1.92) In the study, the most common adverse reactions (> 20%, incidence of darzalex VTD group ≥ 5%) included infusion reaction, nausea, fever, upper respiratory tract infection and bronchitis Serious adverse reactions in darzalex VTD group were higher than that in VTD group, which were bronchitis (2% vs < 1%) and pneumonia (6% vs 4%) Philippe Moreau, chief investigator of the study and director of Hematology Department of Nantes University Hospital in France, previously said: "the critical Cassiopeia study is one of the largest transplantation studies ever conducted in patients with multiple myeloma, and also the largest study conducted with darzalex It is very important for patients to obtain deep remission from the first-line treatment, and casiopeia research results confirm that for patients with newly diagnosed multiple myeloma, adding darzalex to the VTD program before and after transplantation can significantly improve the depth of patients' remission " At the end of June this year, darzalex combined with lenalidomide and dexamethasone was approved by the US FDA for use in newly diagnosed multiple myeloma (mm) patients who are not suitable for autologous stem cell transplantation (ASCT) In the phase III Maia (mmy3008) study, the DRD regimen significantly reduced the risk of disease progression or death by 44% (HR = 0.56, 95% CI: 0.43-0.73, P < 0.0001) compared with the lenalidomide plus dexamethasone regimen (RD) The median PFS in the DRD group was not reached, and the median PFS in the RD group was 31.9 months In addition, compared with RD, DRD achieves a deeper level of remission, including improved complete remission (CR) or better remission (48% vs 25%), very good partial remission (vgpr) or better remission (79% vs 53%), and total remission (93% vs 81%) Compared with RD, the negative rate of MRD induced by DRD was more than three times higher (24% vs 7%) The proportion of patients with severe complete remission (SCR) after darzalex induction and consolidation therapy was significantly higher Darzalex is the first CD38 mediated and cytolytic antibody drug approved in the world It has broad-spectrum killing activity and can target the transmembrane extracellular enzyme CD38 which is highly expressed on the surface of multiple myeloma and multiple solid tumor cells It can induce the rapid death of tumor cells through a variety of immune-mediated mechanisms, including complementary dependent cytotoxicity (CDC) and antibody dependent fine Cell mediated cytotoxicity (ADCC), antibody dependent phagocytosis (ADCP) and apoptosis (apoptosis) In addition, darzalex has also been proved to be able to target immunosuppressive cells in tumor microenvironment to show immunoregulatory activity Darzalex was licensed by Janssen biotechnology from genmab in 2012 It is a product developed by Johnson & Johnson In addition to multiple myeloma, darzalex has the potential to treat other types of tumors with high expression of CD38 molecules, including diffuse large B cell lymphoblastic carcinoma (DLBCL) and chronic lymphoblastic leukemia CLL, all, PCL, AML, FL and MCL In 2018, darzalex's global sales reached $2.025 billion (up 63.0% from $1.242 billion in 2017) Evaluatepharma, a pharmaceutical market research firm, predicts that darzalex's global sales will reach US $6.033 billion in 2024, and that the drug will also become a key product for Johnson & Johnson's future growth Original source: CHMP grants positive operation for expanded use of darzalex (daratomab) in combination with bortezomib, thalidomide and dexamethasone (VTD) for patients with newly diagnosed multiple myeloma who are transform eligible