Multiple myeloma combined therapy! Johnson & Johnson darzalex + kyrolis + dexamethasone three drug program (KDD) in the United States to submit an application!

February 12, 2020 / BIOON / -- Janssen Pharmaceutical, a subsidiary of JNJ, recently announced that it has submitted a report to the U.S Food and Drug Administration (FDA) ）An application for permission to supplement biological products (SBLA) was submitted to seek approval of darzalex (daratumumab), kyperolis (carfilzomib, kafezomib) and dexamethasone for the treatment of recurrent or refractory multiple myeloma (R / RMM) This SBLA is based on the results of the third candor study (nct03158688) It is worth mentioning that this is the first phase III study on the treatment of multiple myeloma (mm) by combining darzalex (anti-CD38 monoclonal antibody) and kyprolis (proteasome inhibitor) Candor is a randomized, developmental phase III study conducted as part of the cooperation between Johnson & Johnson and Amgen, sponsored by Amgen and co funded by Janssen research and development company In this study, 466 patients with R / R MM who had received 1-3 previous therapies were enrolled The efficacy and safety of KDD compared with kyrolis and dexamethasone were evaluated In the study, the first group received kyrolis (56mg / m2 twice a week), dexamethasone and darzalex, the second group (control group) received kyrolis (56mg / m2 twice a week) and dexamethasone, all patients received treatment until the disease progressed The primary end point of the study was progression free survival (PFS) The secondary end points included overall remission rate (ORR), minimal residual disease (MRD), and overall survival period (OS) PFS is defined as randomization time until disease progression or all-cause death The results of the study were presented at the annual meeting of the American Society of Hematology (ash) in 2019 The data showed that the median follow-up period was 17 months, and the study reached the primary end point of PFS: compared with the KD treatment group, the risk of disease progression or death in the KDD treatment group was significantly reduced by 37% (HR = 0.630; 95% CI: 0.464,0.854; P = 0.0014) The median PFS was 15.8 months in the KD group, but not yet in the KD group In addition to reaching the primary end point, compared with KD, KDD also showed significant efficacy in key secondary end points, including orr (84.3% vs 74.7%, P = 0.0040), MRD negative complete remission rate (12.5% vs 1.3%, nearly 10 times higher, P < 0.0001), OS (the median of both groups was not reached, HR = 0.75; 95% CI: 0.49, 1.13; P = 0.08) In the study, the safety of the KDD protocol was consistent with the known safety of each drug in the protocol The most frequently reported adverse events (incidence of KDD ≥ 20% in two treatment groups) were thrombocytopenia, anemia, diarrhea, hypertension, upper respiratory tract infection, fatigue and dyspnea Compared with the KD group, the incidence of grade 3, serious and fatal adverse events was higher in the KDD group The rates of discontinuation due to adverse events were similar in the two groups Multiple myeloma (mm) is an incurable hematological malignancy characterized by remission and recurrent circulation The disease is a very aggressive disease, affecting the plasma cells in the bone marrow, which will replace the normal cells in the bone marrow It is estimated that 32270 people will be diagnosed and 12830 people will die of the disease by 2020 Although some MM patients have no symptoms, most of them are diagnosed with related symptoms, such as fracture or pain, low RBC count, fatigue, high calcium level, kidney problems or infection Darzalex was first approved for marketing in November 2015 It 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 Through a variety of immune-mediated mechanisms, it can induce the rapid death of tumor cells, including complementary dependency fine Cytotoxicity (CDC), antibody dependent cell-mediated cytotoxicity (ADCC), antibody dependent cell 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 Kyprolis was first approved for marketing in July 2012 It is an irreversible proteasome inhibitor administered intravenously Proteasome plays an important role in cell function and growth, and can degrade damaged or no longer needed proteins Kyrolis has been shown to block proteasome and lead to excessive accumulation of proteins in cells In some cells, kyrolis can cause cell death, especially in multiple myeloma cells, which is because these cells are more likely to contain high levels of abnormal proteins At present, darzalex and kyrolis have become important basic therapies for multiple myeloma (mm) The results from the candor study provide strong evidence that KDD regimen has deep and lasting remission in patients with recurrent diseases The combination of kypropris (proteasome inhibitor) and darzalex (anti-CD38 monoclonal antibody) is a promising new method for the treatment of relapsed or refractory multiple myeloma Original source: Janssen announcements submission to U.S FDA for new darzalex (daratumumab) - based combination regions for patients with relapsed / regenerative multiple myeloma