Multiple myeloma new program! Amgen / Johnson kyrolis + dexamethasone + darzalex (KDD) phase III clinical manifestation of deep lasting remission!

December 12, 2019 / BIOON / -- the 61st annual meeting of the American Society of Hematology (ash2019) was recently held in Orlando, Florida, USA At the meeting, Amgen announced the results of candor (nct03158688) phase III clinical study on the treatment of recurrent or refractory multiple myeloma (R / RMM) by kyprolis (carfilzomib, kafezomib), dexamethasone and darzalex (kratamumab) It is worth mentioning that this is the first phase III study on the treatment of multiple myeloma by the combination of kyprolis (proteasome inhibitor) and darzalex (anti-CD38 mAb) Candor is a randomized, developmental phase III study conducted as part of a collaboration with Johnson & Johnson's Janssen, who co funded the study under the agreement In this study, 466 patients with R / R MM who had received 1-3 kinds of therapy before were enrolled The efficacy and safety of KDD regimen compared with kyrolis and dexamethasone two drug regimen (KD) 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 showed that after a median follow-up of 17 months, 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 this 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 David M Reese, MD, executive vice president of Amgen research and development, said: "the results of 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 " Multiple myeloma (mm) is an incurable hematological malignancy characterized by remission and recurrent circulation It is a rare and aggressive disease, accounting for about 1% of all cancer types Worldwide, about 160000 people are diagnosed with mm every year, and 106000 people die every year Proteasome plays an important role in cell function and growth, and can degrade damaged or no longer needed proteins Kyperolis is an irreversible proteasome inhibitor administered intravenously, which has been proved to block proteasome and lead to excessive accumulation of protein 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 Since kyrolis was first approved in 2012, about 130000 patients worldwide have been treated In the United States, keytruda has approved the following indications: (1) combination of dexamethasone, or combination of dexamethasone and lenalidomide, for the treatment of patients with recurrent or refractory multiple myeloma (R / R mm) who have previously received 1-3 therapies; (2) as a single drug therapy, for the treatment of R / R MM patients who have received one or more therapies 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 In the United States, darzalex was approved by FDA for the first time in November 2015 In 2018, the global sales volume has exceeded 2 billion US dollars The indications of darzalex include: as a single drug and a variety of combinations of drugs, the treatment of newly diagnosed MM patients, as well as recurrent or refractory MM patients Original source: Amgen data from phase 3 candor study combining kyprolis ® (carfilzomib) and darzalex ® (daratomab) to be presented during late breaking session at American Society of geography annual meeting