First line treatment does not accord with the transplantation of multiple myeloma! The plan of darzalex + RD is approved by the European Union!

November 20, 2019 / Biovalley BIOON / - Johnson & Johnson's Janssen Pharmaceutical recently announced that the European Commission (EC) has approved the darzalex (daratumab) combined with lenalidomide and dexamethasone three drug program (DRD) for newly diagnosed multiple myeloma (mm) patients who do not meet the qualification of autologous stem cell transplantation (ASCT) Previously, darzalex combined with bortezomib, melphalan and prednisone (d-vmp) have been approved by EC for the treatment of newly diagnosed MM patients who are not qualified for ASCT The approved DRD program will provide a new treatment option for the newly diagnosed MM patients who are not qualified for ASCT in Europe In the United States, DRD three drug program and d-vmp four drug program have been approved by FDA for the newly diagnosed MM patients who do not meet the ASCT qualification The approval of the three drug regimen of DRD is based on the data of phase III clinical study Maia (mmy3008) This study was conducted in newly diagnosed MM patients who were not suitable for high-dose chemotherapy and ASCT, and evaluated the efficacy and safety of DRD compared with lenalidomide and dexamethasone The results were published in the New England Journal of Medicine (NEJM) and presented at the annual meeting of the American Society of Hematology (ash) in 2018 Data showed that median follow-up of 28 months showed that the study reached the primary end point of improving progression free survival (PFS): a preplanned mid-term analysis conducted by the independent data monitoring committee (IDMC) showed a significant 44% reduction in the risk of disease progression or death in the DRD group compared with the RD group (HR = 0.56, 95% CI: 0.43-0.73, P < 0.0001) 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 achieved a deeper level of remission, including improved complete or better remission rate (48% vs 25%), and overall remission rate (93% vs 81%) In the study, the most common 3 / 4-stage adverse events (≥ 10%) in the DRD group included neutropenia (50%), lymphopenia (15%), pneumonia (14%) and anemia (12%) 41% of the patients had transfusion related reactions, 3% of them were grade 3 / 4 The security of darzalex is consistent with previous studies 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 authorized by Janssen biotechnology company 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 lymphocarcinoma (DLBCL) and chronic lymphoblastic leukemia CLL, all, PCL, AML, FL and MCL Darzalex was approved for marketing in November 2015 At present, it has been approved for several treatment indications, which are different in different countries and regions, including: (1) darzalex combined with bortezomib, thalidomide and dexamethasone four drug regimen (d-vtd) The first-line treatment is in line with the autologous stem cells Newly diagnosed multiple myeloma (mm) patients eligible for transplantation (ASCT); (2) darzalex First line treatment of newly diagnosed MM patients who are not qualified for ASCT with combination of lenalidomide and dexamethasone (DRD); (3) first line treatment of newly diagnosed MM patients who are not qualified for ASCT with combination of darzalex and bortezomib, Malan and prednisone (d-vmp); (4) combination of lenalidomide and dexamethasone with combination of bortezomib and dexamethasone for previous connection Mm adult patients who have received at least one therapy; (5) combination of palmatine and dexamethasone for MM adult patients who have received at least two previous therapies (including lenalidomide and proteasome inhibitor [PI]); (6) as a single drug therapy for at least three previous therapies (including a proteasome inhibitor [PI] and an immunomodulator [IMID]) or for pi Mm adult patients with dual refractory to immunomodulators In February this year, darzalex received FDA approval for a single dose regimen This program will make a choice for medical and health professionals when they treat MM patients according to their needs The first intravenous infusion of darzalex will be divided into two consecutive days of intravenous infusion from a single infusion In July this year, darzalex subcutaneous injection type was applied for listing in the US and Europe Phase III clinical study data showed that darzalex subcutaneous injection preparation and darzalex intravenous injection preparation had non inferiority in efficacy (total remission rate: 41% vs 37%, ratio = 1.11, 95% CI: 0.89-1.37) and pharmacokinetics (daratumab Valley concentration [ctrough]: 499mg / ml vs 463mg / ml, ratio = 108%, 90% CI: 90% - 122%), and the administration time was shorter (5 minutes vs.122%) The incidence of transfusion related reactions was lower (13% vs 35%) According to Johnson & Johnson's 2019 performance report, darzalex's sales in the first three quarters of this year reached $2.168 billion, an increase of 50.4% over the same period last year Evaluatepharma, a pharmaceutical market research firm, predicted that darzalex's global sales in 2024 would reach US $6.033 billion, and that the drug would also become a key product for Johnson & Johnson's future growth Original source: Janssen receives EU marketing authorization for darzalex ® (daratomab) in combination with lenalidomide and dexamethasone for patients with newly diagnosed multiple myeloma who are transform incoming