First line treatment does not accord with stem cell transplantation of multiple myeloma! Darzalex + Rd regimen significantly prolonged progression free survival

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, Janssen Pharmaceutical, a subsidiary of JNJ, released the long-term follow-up data of phase III clinical study Maia (mmy3008) This study was carried out in patients with newly diagnosed multiple myeloma (ndmm) who were not suitable for ASCT The efficacy and safety of the three drug regimen (d-rd) of targeted anticancer drug darzalex (daratumab) in combination with lenalidomide and dexamethasone were evaluated and compared with the two drug regimen (RD) of lenalidomide and dexamethasone The results showed that compared with RD regimen, d-rd regimen significantly reduced the risk of disease progression or death, and significantly increased the overall remission rate (OS) Maia (mmy3008) is a randomized, open label, multicenter phase III study in which 737 newly diagnosed patients (aged 45-90; median age 73) with multiple myeloma who are not suitable for high-dose chemotherapy and autologous stem cell transplantation (ASCT) were enrolled In the study, patients were randomly assigned to receive darzalex + lenalidomide + dexamethasone three drug regimen (d-rd) or lenalidomide + dexamethasone two drug regimen In the d-rd treatment group, patients received 16 mg / kg darzalex: once a week in the first two cycles, once every two weeks in the third six cycles, once in the seventh cycle and once every four weeks after that until the disease progresses The primary end point was progression free survival (PFS) The additional data of long-term follow-up (median 36.4 months) published at this ash meeting showed that compared with RD regimen, d-rd regimen continued to significantly reduce the risk of disease progression or death by ≥ 44% (HR = 0.56; 95% CI: 0.44-0.71; P < 0.0001) After three years of follow-up, there were no new safety issues in the d-rd protocol group In addition, the time from randomization to lower first-line treatment or death (pfs2) was favorable for the d-rd treatment group (HR = 0.69; 95% CI: 0.53-0.91; P = 0.0079) The updated overall remission rate (ORR) was 93% in the d-rd group and 82% in the RD group (P < 0.0001); the strict complete remission (SCR) was 33% in the d-rd group and 14% in the RD group (P < 0.0001); the very good partial or better remission (≥ vgpr) was 80% in the d-rd group and 55% in the RD group (P < 0.0001); the complete or better remission (≥ CR) was 80% in the d-rd group and 55% in the RD group (P < 0.0001) -49% in RD group and 27% in RD group (P < 0.0001) In terms of safety, the common level 3 / 4 adverse events (teaes) in patients with d-rd treatment group were neutropenia (51% vs 35%), lymphopenia (15% vs 11%), pneumonia (15% vs 9%), anemia (14% vs 21%), leukopenia (11% vs 6%) and hypokalemia (10% vs 10%) The most common serious teae in the d-rd group was pneumonia (14% vs 9%) The most common level 3 / 4 infection was 36% in the d-rd group and 27% in the RD group 9% of the patients in the d-rd group stopped treatment due to teae, while 18% in the RD group 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: darzalex? (dalatumab) shows overall survival benefit and continued improvement in progress free survival in patients with newly diagnosed multiple myeloma who are incoming